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Deep vein thrombosis landmark trials in treatment

2012-05-28T03:23:14Z

Kashish Goel: /* EINSTEIN Study{{cite journal |author=Bauersachs R, Berkowitz SD, Brenner B, et al. |title=Oral rivaroxaban for symptomatic venous thromboembolism |journal=N. Engl. J. Med. |volume=363 |issue=26 |pages=2499–510 |year=2010 |month=December |pmid...

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==
1. PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) study<ref name="pmid16009794">{{cite journal |author= |title=Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study |journal=Circulation |volume=112 |issue=3 |pages=416–22 |year=2005 |month=July |pmid=16009794 |doi=10.1161/CIRCULATIONAHA.104.512834 |url=}}</ref>

* '''Objective:''' Eight-year follow-up study to assess the long-term effect of [[IVC filter]]s.
* '''Methods:''' Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and [[post-thrombotic syndrome]] were obtained once a year for up to 8 years.
* '''Results:''' Symptomatic [[PE]] occurred less frequently in the [[IVC filter]] group (6.2%) compared with the no-filter group (15.1%, p=0.008). However, [[DVT]] was more frequent in the filter group (35.7%) compared with the no-filter group (27.5%, p=0.042). Postthrombotic syndrome and mortality rates were almost similar in both groups.
* '''Conclusions:''' [[IVC filter]] reduced the risk of [[P]], but increased that of [[DVT]] and had no effect on survival.

==Newer anticoagulants==

===Rivaroxaban===

====EINSTEIN Study<ref name="pmid21128814">{{cite journal |author=Bauersachs R, Berkowitz SD, Brenner B, ''et al.'' |title=Oral rivaroxaban for symptomatic venous thromboembolism |journal=N. Engl. J. Med. |volume=363 |issue=26 |pages=2499–510 |year=2010 |month=December |pmid=21128814 |doi=10.1056/NEJMoa1007903 |url=}}</ref>====
* '''Objective:''' To determine the safety and efficacy of [[Rivaroxaban]] for treatment of acute [[VTE]] as compared to warfarin.
* '''Methods:''' An open-label, randomized, event-driven, noninferiority study comparing oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily)) with subcutaneous enoxaparin followed by vitamin K antagonist. The investigators also conducted a superiority study, that randomized patients to rivaroxaban (20 mg once daily) or placebo for an additional 6-12 months, after completing 6 to 12 months of [[VTE]] treatment.
* '''Results:''' Rivaroxaban was non-inferior to enoxaparin and vitamin K antagonit in terms of primary outcome of recurrent [[VTE]] (2.1% in rovaroxaban group vs. 3.0% in other group, p<0.0001 for non-inferiority). Major bleeding occurred in 0.8% of the patients on rivaroxaban versus 1.2% in the warfarin group (HR 0.65, 95% CI 0.33-1.30). Nonmajor bleeding was also similar in both groups (HR 0.97, 95% CI 0.76-1.22). In the continued-treatment study, rivaroxaban had superior efficacy (1.3% vs. 7.1% in placebo group; HR 0.18, 95% CI 0.09-0.39).
* '''Conclusions:''' Rivaroxaban was non-inferior to warfarin for initial treatment of acute [[VTE]], with a similar safety profile. It is also safe and effective for continued treatment of [[VTE]].

===Dabigatran===

====RE-COVER Study<ref name="pmid19966341">{{cite journal |author=Schulman S, Kearon C, Kakkar AK, ''et al.'' |title=Dabigatran versus warfarin in the treatment of acute venous thromboembolism |journal=N. Engl. J. Med. |volume=361 |issue=24 |pages=2342–52 |year=2009 |month=December |pmid=19966341 |doi=10.1056/NEJMoa0906598 |url=}}</ref>====
* '''Objective:''' To compare the effectiveness and safety of [[Dabigatran]] with warfarin therapy for treatment of [[VTE]].
* '''Methods:''' A randomized, double-blind, non-inferiority trial was conducted, involving patients with acute [[VTE]] who were initially given parenteral anticoagulation for 8-11 days, and then randomized to dabigatran 150 mg twice daily or warfarin with a therapeutic INR range of 2.0-3.0.
* '''Results:''' A total of 1274 patients were randomized to dabigatran and 1265 received warfarin therapy. The number of recurrent thromboembolism was almost similar (2.4% with dabigatran vs. 2.1% with warfarin, non-inferiority p <0.001). Major bleeding occurred in 1.6% of patients on dabigatran compared with 1.9% on warfarin (HR for dabigatran 0.82, 95% CI 045-1.48). The number of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in both groups. [[FDA Adverse Events|Adverse events]] occurred in 9% patients on dabigatran vs. 6.8% on warfarin (p=0.05), leading to discontinuation of the drug.

* '''Conclusions:''' Dabigatran is as effective and safe as warfarin for the treatment of acute [[VTE]]. This drug does not need monitoring as compared to warfarin.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-28T03:22:52Z

Kashish Goel: /* Rivoraxaban */

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==
1. PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) study<ref name="pmid16009794">{{cite journal |author= |title=Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study |journal=Circulation |volume=112 |issue=3 |pages=416–22 |year=2005 |month=July |pmid=16009794 |doi=10.1161/CIRCULATIONAHA.104.512834 |url=}}</ref>

* '''Objective:''' Eight-year follow-up study to assess the long-term effect of [[IVC filter]]s.
* '''Methods:''' Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and [[post-thrombotic syndrome]] were obtained once a year for up to 8 years.
* '''Results:''' Symptomatic [[PE]] occurred less frequently in the [[IVC filter]] group (6.2%) compared with the no-filter group (15.1%, p=0.008). However, [[DVT]] was more frequent in the filter group (35.7%) compared with the no-filter group (27.5%, p=0.042). Postthrombotic syndrome and mortality rates were almost similar in both groups.
* '''Conclusions:''' [[IVC filter]] reduced the risk of [[P]], but increased that of [[DVT]] and had no effect on survival.

==Newer anticoagulants==

===Rivaroxaban===

====EINSTEIN Study<ref name="pmid21128814">{{cite journal |author=Bauersachs R, Berkowitz SD, Brenner B, ''et al.'' |title=Oral rivaroxaban for symptomatic venous thromboembolism |journal=N. Engl. J. Med. |volume=363 |issue=26 |pages=2499–510 |year=2010 |month=December |pmid=21128814 |doi=10.1056/NEJMoa1007903 |url=}}</ref>====
* '''Objective:''' To determine the safety and efficacy of [[Rivaroxaban]] for treatment of acute [[VTE]] as compared to warfarin.
* Methods: An open-label, randomized, event-driven, noninferiority study comparing oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily)) with subcutaneous enoxaparin followed by vitamin K antagonist. The investigators also conducted a superiority study, that randomized patients to rivaroxaban (20 mg once daily) or placebo for an additional 6-12 months, after completing 6 to 12 months of [[VTE]] treatment.
* Results: Rivaroxaban was non-inferior to enoxaparin and vitamin K antagonit in terms of primary outcome of recurrent [[VTE]] (2.1% in rovaroxaban group vs. 3.0% in other group, p<0.0001 for non-inferiority). Major bleeding occurred in 0.8% of the patients on rivaroxaban versus 1.2% in the warfarin group (HR 0.65, 95% CI 0.33-1.30). Nonmajor bleeding was also similar in both groups (HR 0.97, 95% CI 0.76-1.22). In the continued-treatment study, rivaroxaban had superior efficacy (1.3% vs. 7.1% in placebo group; HR 0.18, 95% CI 0.09-0.39).
* COnclusions: Rivaroxaban was non-inferior to warfarin for initial treatment of acute [[VTE]], with a similar safety profile. It is also safe and effective for continued treatment of [[VTE]].

===Dabigatran===

====RE-COVER Study<ref name="pmid19966341">{{cite journal |author=Schulman S, Kearon C, Kakkar AK, ''et al.'' |title=Dabigatran versus warfarin in the treatment of acute venous thromboembolism |journal=N. Engl. J. Med. |volume=361 |issue=24 |pages=2342–52 |year=2009 |month=December |pmid=19966341 |doi=10.1056/NEJMoa0906598 |url=}}</ref>====
* '''Objective:''' To compare the effectiveness and safety of [[Dabigatran]] with warfarin therapy for treatment of [[VTE]].
* '''Methods:''' A randomized, double-blind, non-inferiority trial was conducted, involving patients with acute [[VTE]] who were initially given parenteral anticoagulation for 8-11 days, and then randomized to dabigatran 150 mg twice daily or warfarin with a therapeutic INR range of 2.0-3.0.
* '''Results:''' A total of 1274 patients were randomized to dabigatran and 1265 received warfarin therapy. The number of recurrent thromboembolism was almost similar (2.4% with dabigatran vs. 2.1% with warfarin, non-inferiority p <0.001). Major bleeding occurred in 1.6% of patients on dabigatran compared with 1.9% on warfarin (HR for dabigatran 0.82, 95% CI 045-1.48). The number of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in both groups. [[FDA Adverse Events|Adverse events]] occurred in 9% patients on dabigatran vs. 6.8% on warfarin (p=0.05), leading to discontinuation of the drug.

* '''Conclusions:''' Dabigatran is as effective and safe as warfarin for the treatment of acute [[VTE]]. This drug does not need monitoring as compared to warfarin.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

FDA Adverse Events

2012-05-28T02:09:39Z

Kashish Goel: Created page with "{{CMG}}; '''Associate Editor-In-Chief''': Kashish Goel,M.D. ==FDA definition of Adverse Event== {{cquote| '''What is a Serious Adverse Event?''' '''A..."

{{CMG}}; '''Associate Editor-In-Chief''': [[User:Kashish Goel|Kashish Goel,M.D.]]

==FDA definition of Adverse Event==
{{cquote|

'''What is a Serious Adverse Event?'''

'''An adverse event is any undesirable experience associated with the use of a medical product in a patient.'''

The event is serious and should be reported to FDA when the patient outcome is:

'''Death'''
* Report if you suspect that the death was an outcome of the adverse event, and include the date if known.

'''Life-threatening'''
* Report if suspected that the patient was at substantial risk of dying at the time of the adverse event, or use or continued use of the device or other medical product might have resulted in the death of the patient.

'''Hospitalization (initial or prolonged)'''
* Report if admission to the hospital or prolongation of hospitalization was a result of the adverse event.
* Emergency room visits that do not result in admission to the hospital should be evaluated for one of the other serious outcomes (e.g., life-threatening; required intervention to prevent permanent impairment or damage; other serious medically important event).

'''Disability or Permanent Damage'''
* Report if the adverse event resulted in a substantial disruption of a person's ability to conduct normal life functions, i.e., the adverse event resulted in a significant, persistent or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities and/or quality of life.

'''Congenital Anomaly/Birth Defect'''
* Report if you suspect that exposure to a medical product prior to conception or during pregnancy may have resulted in an adverse outcome in the child.

'''Required Intervention to Prevent Permanent Impairment or Damage (Devices)'''
* Report if you believe that medical or surgical intervention was necessary to preclude permanent impairment of a body function, or prevent permanent damage to a body structure, either situation suspected to be due to the use of a medical product.

'''Other Serious (Important Medical Events)'''
* Report when the event does not fit the other outcomes, but the event may jeopardize the patient and may require medical or surgical intervention (treatment) to prevent one of the other outcomes. Examples include allergic brochospasm (a serious problem with breathing) requiring treatment in an emergency room, serious blood dyscrasias (blood disorders) or seizures/convulsions that do not result in hospitalization. The development of drug dependence or drug abuse would also be examples of important medical events.}}

More information about this can be found on this website: http://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm.

==References==
{{reflist|2}}

[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-28T02:06:08Z

Kashish Goel:

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==
1. PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) study<ref name="pmid16009794">{{cite journal |author= |title=Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study |journal=Circulation |volume=112 |issue=3 |pages=416–22 |year=2005 |month=July |pmid=16009794 |doi=10.1161/CIRCULATIONAHA.104.512834 |url=}}</ref>

* '''Objective:''' Eight-year follow-up study to assess the long-term effect of [[IVC filter]]s.
* '''Methods:''' Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and [[post-thrombotic syndrome]] were obtained once a year for up to 8 years.
* '''Results:''' Symptomatic [[PE]] occurred less frequently in the [[IVC filter]] group (6.2%) compared with the no-filter group (15.1%, p=0.008). However, [[DVT]] was more frequent in the filter group (35.7%) compared with the no-filter group (27.5%, p=0.042). Postthrombotic syndrome and mortality rates were almost similar in both groups.
* '''Conclusions:''' [[IVC filter]] reduced the risk of [[P]], but increased that of [[DVT]] and had no effect on survival.

==Newer anticoagulants==

===Rivoraxaban===

===Dabigatran===

====RE-COVER Study<ref name="pmid19966341">{{cite journal |author=Schulman S, Kearon C, Kakkar AK, ''et al.'' |title=Dabigatran versus warfarin in the treatment of acute venous thromboembolism |journal=N. Engl. J. Med. |volume=361 |issue=24 |pages=2342–52 |year=2009 |month=December |pmid=19966341 |doi=10.1056/NEJMoa0906598 |url=}}</ref>====
* '''Objective:''' To compare the effectiveness and safety of [[Dabigatran]] with warfarin therapy for treatment of [[VTE]].
* '''Methods:''' A randomized, double-blind, non-inferiority trial was conducted, involving patients with acute [[VTE]] who were initially given parenteral anticoagulation for 8-11 days, and then randomized to dabigatran 150 mg twice daily or warfarin with a therapeutic INR range of 2.0-3.0.
* '''Results:''' A total of 1274 patients were randomized to dabigatran and 1265 received warfarin therapy. The number of recurrent thromboembolism was almost similar (2.4% with dabigatran vs. 2.1% with warfarin, non-inferiority p <0.001). Major bleeding occurred in 1.6% of patients on dabigatran compared with 1.9% on warfarin (HR for dabigatran 0.82, 95% CI 045-1.48). The number of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in both groups. [[FDA Adverse Events|Adverse events]] occurred in 9% patients on dabigatran vs. 6.8% on warfarin (p=0.05), leading to discontinuation of the drug.

* '''Conclusions:''' Dabigatran is as effective and safe as warfarin for the treatment of acute [[VTE]]. This drug does not need monitoring as compared to warfarin.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-28T01:56:25Z

Kashish Goel: /* RE-COVER Study */

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==
1. PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) study<ref name="pmid16009794">{{cite journal |author= |title=Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study |journal=Circulation |volume=112 |issue=3 |pages=416–22 |year=2005 |month=July |pmid=16009794 |doi=10.1161/CIRCULATIONAHA.104.512834 |url=}}</ref>

* '''Objective:''' Eight-year follow-up study to assess the long-term effect of [[IVC filter]]s.
* '''Methods:''' Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and [[post-thrombotic syndrome]] were obtained once a year for up to 8 years.
* '''Results:''' Symptomatic [[PE]] occurred less frequently in the [[IVC filter]] group (6.2%) compared with the no-filter group (15.1%, p=0.008). However, [[DVT]] was more frequent in the filter group (35.7%) compared with the no-filter group (27.5%, p=0.042). Postthrombotic syndrome and mortality rates were almost similar in both groups.
* '''Conclusions:''' [[IVC filter]] reduced the risk of [[P]], but increased that of [[DVT]] and had no effect on survival.

==Newer anticoagulants==

===Rivoraxaban===

===Dabigatran===

====RE-COVER Study====
* '''Objective:''' To compare the effectiveness and safety of [[Dabigatran]] with warfarin therapy for treatment of [[VTE]].
* '''Methods:''' A randomized, double-blind, non-inferiority trial was conducted, involving patients with acute [[VTE]] who were initially given parenteral anticoagulation for 8-11 days, and then randomized to dabigatran 150 mg twice daily or warfarin with a therapeutic INR range of 2.0-3.0.
* '''Results:''' A total of 1274 patients were randomized to dabigatran and 1265 received warfarin therapy. The number of recurrent thromboembolism was almost similar (2.4% with dabigatran vs. 2.1% with warfarin, non-inferiority p <0.001). Major bleeding occurred in 1.6% of patients on dabigatran compared with 1.9% on warfarin (HR for dabigatran 0.82, 95% CI 045-1.48). The number of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in both groups. [[FDA Adverse Events|Adverse events]] occurred in 9% patients on dabigatran vs. 6.8% on warfarin (p=0.05), leading to discontinuation of the drug.

* '''Conclusions:''' Dabigatran is as effective and safe as warfarin for the treatment of acute [[VTE]]. This drug does not need monitoring as compared to warfarin.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-28T01:53:19Z

Kashish Goel: /* Dabigatran */

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==
1. PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) study<ref name="pmid16009794">{{cite journal |author= |title=Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study |journal=Circulation |volume=112 |issue=3 |pages=416–22 |year=2005 |month=July |pmid=16009794 |doi=10.1161/CIRCULATIONAHA.104.512834 |url=}}</ref>

* '''Objective:''' Eight-year follow-up study to assess the long-term effect of [[IVC filter]]s.
* '''Methods:''' Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and [[post-thrombotic syndrome]] were obtained once a year for up to 8 years.
* '''Results:''' Symptomatic [[PE]] occurred less frequently in the [[IVC filter]] group (6.2%) compared with the no-filter group (15.1%, p=0.008). However, [[DVT]] was more frequent in the filter group (35.7%) compared with the no-filter group (27.5%, p=0.042). Postthrombotic syndrome and mortality rates were almost similar in both groups.
* '''Conclusions:''' [[IVC filter]] reduced the risk of [[P]], but increased that of [[DVT]] and had no effect on survival.

==Newer anticoagulants==

===Rivoraxaban===

===Dabigatran===

====RE-COVER Study====
* Objective: To compare the effectiveness and safety of [[Dabigatran]] with warfarin therapy for treatment of [[VTE]].
* Methods: A randomized, double-blind, non-inferiority trial was conducted, involving patients with acute [[VTE]] who were initially given parenteral anticoagulation for 8-11 days, and then randomized to dabigatran 150 mg twice daily or warfarin with a therapeutic INR range of 2.0-3.0.
* Results: A total of 1274 patients were randomized to dabigatran and 1265 received warfarin therapy. The number of recurrent thromboembolism was almost similar (2.4% with dabigatran vs. 2.1% with warfarin, non-inferiority p <0.001). Major bleeding occurred in 1.6% of patients on dabigatran compared with 1.9% on warfarin (HR for dabigatran 0.82, 95% CI 045-1.48). The number of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in both groups.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-27T20:36:25Z

Kashish Goel: /* Newer anticoagulants */

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==
1. PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) study<ref name="pmid16009794">{{cite journal |author= |title=Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study |journal=Circulation |volume=112 |issue=3 |pages=416–22 |year=2005 |month=July |pmid=16009794 |doi=10.1161/CIRCULATIONAHA.104.512834 |url=}}</ref>

* '''Objective:''' Eight-year follow-up study to assess the long-term effect of [[IVC filter]]s.
* '''Methods:''' Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and [[post-thrombotic syndrome]] were obtained once a year for up to 8 years.
* '''Results:''' Symptomatic [[PE]] occurred less frequently in the [[IVC filter]] group (6.2%) compared with the no-filter group (15.1%, p=0.008). However, [[DVT]] was more frequent in the filter group (35.7%) compared with the no-filter group (27.5%, p=0.042). Postthrombotic syndrome and mortality rates were almost similar in both groups.
* '''Conclusions:''' [[IVC filter]] reduced the risk of [[P]], but increased that of [[DVT]] and had no effect on survival.

==Newer anticoagulants==

===Rivoraxaban===

===Dabigatran===

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-27T20:35:51Z

Kashish Goel: /* Use of IVC filters */

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==
1. PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) study<ref name="pmid16009794">{{cite journal |author= |title=Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study |journal=Circulation |volume=112 |issue=3 |pages=416–22 |year=2005 |month=July |pmid=16009794 |doi=10.1161/CIRCULATIONAHA.104.512834 |url=}}</ref>

* '''Objective:''' Eight-year follow-up study to assess the long-term effect of [[IVC filter]]s.
* '''Methods:''' Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and [[post-thrombotic syndrome]] were obtained once a year for up to 8 years.
* '''Results:''' Symptomatic [[PE]] occurred less frequently in the [[IVC filter]] group (6.2%) compared with the no-filter group (15.1%, p=0.008). However, [[DVT]] was more frequent in the filter group (35.7%) compared with the no-filter group (27.5%, p=0.042). Postthrombotic syndrome and mortality rates were almost similar in both groups.
* '''Conclusions:''' [[IVC filter]] reduced the risk of [[P]], but increased that of [[DVT]] and had no effect on survival.

==Newer anticoagulants==

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-27T20:21:09Z

Kashish Goel: /* Catheter-directed thrombolysis{{cite journal |author=Enden T, Kløw NE, Sandvik L, et al. |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting o...

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Trials assessing different formulations of heparin for treatment==
===Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]<ref name="pmid15159264">{{cite journal |author=Prandoni P, Carnovali M, Marchiori A |title=Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism |journal=Arch. Intern. Med. |volume=164 |issue=10 |pages=1077–83 |year=2004 |month=May |pmid=15159264 |doi=10.1001/archinte.164.10.1077 |url=}}</ref>
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose subcutaneous unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2. Fixed-Dose Heparin (FIDO) trial<ref name="pmid16926353">{{cite journal |author=Kearon C, Ginsberg JS, Julian JA, ''et al.'' |title=Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism |journal=JAMA |volume=296 |issue=8 |pages=935–42 |year=2006 |month=August |pmid=16926353 |doi=10.1001/jama.296.8.935 |url=}}</ref>
* '''Objective:''' Compare subcutaneous [[unfractionated heparin]] with [[LMWH]] for treatment of [[VTE]]
* '''Methods:''' Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients with [[VTE]], who were randomized to [[unfractionated heparin]] at an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours and [[LMWH]] at a fixed dose of 100 U/kg every 12 hours. Both treatments were given as outpatients.
* '''Results:''' The are of recurrent [[VTE]] (3.8% and 3.4%) and major bleeding (1.1% and 1.4%) was almost similar in the [[UFH]] and [[LMWH]] groups, respectively.
* '''Conclusions:''' Fixed dose subcutaneous [[UFH]] is as effective and safe as [[LMWH]] for treatment of [[VTE]] in an outpatient setting.

3. Polish multi center trial<ref name="pmid1325076">{{cite journal |author=Lopaciuk S, Meissner AJ, Filipecki S, ''et al.'' |title=Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial |journal=Thromb. Haemost. |volume=68 |issue=1 |pages=14–8 |year=1992 |month=July |pmid=1325076 |doi= |url=}}</ref>
* '''Methods:''' A total of 149 patients with [[DVT]] were randomly assigned to subcutaneous [[LMWH]] or subcutaneous [[UFH]] for 10 days.
* '''Results:''' One symptomatic nonfatal [[PE]], two rethromboses and one major leading was noted in the [[UFH]] group, compared to none in [[LMWH]] group.
* '''Conculusions:''' Subcutaneous fixed-dose [[LMWH]] is as effective and safe as subcutaneous [[UFH]] in treatment of [[DVT]].

===Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin===
1. Cochrane meta-analysis<ref name="pmid20824828">{{cite journal |author=Erkens PM, Prins MH |title=Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=9 |pages=CD001100 |year=2010 |pmid=20824828 |doi=10.1002/14651858.CD001100.pub3 |url=}}</ref>
* '''Objective:''' To compare the effectiveness of [[LMWH]] with [[UFH]] for [[VTE]] treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized controlled trials comparing the fixed dose subcutaneous [[LMWH]] with adjusted dose intravenous or subcutaneous [[UFH]] for treatment of [[VTE]] was performed.
* '''Results:''' A total of 23 studies were included in the meta-analysis. Thrombotic complications (3.6% vs. 5.3%; OR, 0.70, 95% CI 0.57-0.85), major hemorrhages (1.1% vs. 1.9%; OR, 0.58, 95% CI 0.40-0.83) and mortality (4.3% vs. 5.8%; OR, 0.77, 95% CI 0.63-0.93) was significantly lower in subjects treated with [[LMWH]] compared with [[UFH]].
* '''Conclusions:''' Subcutaneous [[LMWH]] signficantly reduced the incidence of thrombotic complications, major bleeding and mortality in patients with acute [[VTE]]. It is more effective and safer than [[UFH]] for the initial treatment of [[VTE]].

2. '''Objective:''' Compare the effectiveness of two daily subcutaneous injections of [LMWH]] with intravenous [[UFH]] in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Methods:''' A total of 119 patients with acute [[DVT]] were randomized to either subcutaneous [[LMWH][ or intravenous [[UFH]].
*''' Results:''' Repeat imaging after 5-7 days showed similar improvement in thrombosis in both groups (76% vs. 61%), whereas 2 patients in [[UFH]] group suffered a major bleed compared to 4 patients in [[LMWH]] group. After 22 months of mean follow-up, 6 re-thromboses occurred in the [[UFH]] group compared with 4 in the [[LMWH]] group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Subcutaneous [[LMWH]] is as effective and safe as continuous intravenous [[UFH]] in the treatment of [[DVT]] of the leg.

===Trials regarding the use of Fondaprinux===
1. Matisse Investigators<ref name="pmid15172900">{{cite journal |author=Büller HR, Davidson BL, Decousus H, ''et al.'' |title=Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial |journal=Ann. Intern. Med. |volume=140 |issue=11 |pages=867–73 |year=2004 |month=June |pmid=15172900 |doi= |url=}}</ref>
* '''Objective:''' To compare [[fondaprinux]] with [[LMWH]] for initial treatment of [[DVT]]
* '''Methods:''' A randomized double-blind study randomizing 2205 patients with acute [[DVT]] to [[fondaparinux]] 7.5 mg subcutaneously once daily or enoxaparin for at least 5 days.
* '''Results:''' The rate of recurrent thromboembolic events were similar in the [[fondaparinux]] group (3.9%) and enoxaparin (4.1%) was similar. Major bleeding occurred in 1.1% of patients receiving [[fondaparinux]] compared with 1.2% in patients receiving enoxparin.
* '''Conclusions:''' [[Fondaparinux]] was as effective and safe as Enoxaparin for treatment of acute [[DVT]].

===Meta-analysis assessing LMWH dosing<ref name="pmid16034885">{{cite journal |author=van Dongen CJ, MacGillavry MR, Prins MH |title=Once versus twice daily LMWH for the initial treatment of venous thromboembolism |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003074 |year=2005 |pmid=16034885 |doi=10.1002/14651858.CD003074.pub2 |url=}}</ref>===
* '''Objective:''' To compare the efficacy and safety of once versus rice daily administration of [[LMWH]]
* '''Methods:''' A [[cochrane collaboration]] meta-analysis of randomized clinical trials assessing the dosing of [[LMWH]].
* '''Results:''' A total of 5 studies enrolling 1508 subjects with acute [[VTE]] were included in this meta-analysis. There was no significant difference between the two groups for the risk of recurrent [[VTE]] (OR 0.77, 95% CI 0.40-1.45), in the risk of major hemorrhagic events (OR 1.14, 95% CI 0.62-2.08) or in mortality rates (OR 0.82, 95% CI 0.49-1.39),
* '''Conclusions:''' Once daily [[LMWH]] was as effective and safe as twice daily dosing. However, the increased 95% CI limits imply that there may be a higher risk of recurrent [[VTE]] in patients treated with once daily dosing.

===Meta-analysis of Home versus inpatient treatment of DVT<ref name="pmid11406067">{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003076 |year=2001 |pmid=11406067 |doi=10.1002/14651858.CD003076 |url=}}</ref>===
* '''Objective:''' To compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment.
* '''Methods:''' A [[cochrane collaboration]] meta-analysis was conducted including all randomized controlled trials of home versus hospital treatment of [[DVT]]. The patients were treated with either [[LMWH]] or [[UFH]].
* '''Results:''' Only 2 trials were found, with some inherent limitations including high exclusion rates, partial hospital treatment of many in the [[LMWH]] arms, and comparison of [[UFH]] in hospital with [[LMWH]] at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller trials comparing [[LMWH]] treatment in both home and hospital arms came to the same conclusion.
* '''Conclusions:''' Limited evidence suggested that home treatment of [[DVT]] is preferred by patients and more cost-effective, without any major complications.

==Catheter-directed thrombolysis<ref name="pmid19422443">{{cite journal |author=Enden T, Kløw NE, Sandvik L, ''et al.'' |title=Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency |journal=J. Thromb. Haemost. |volume=7 |issue=8 |pages=1268–75 |year=2009 |month=August |pmid=19422443 |doi=10.1111/j.1538-7836.2009.03464.x |url=}}</ref>==
* '''Objective:''' To assess the efficacy of [[Catheter=Directed thrombolysis|catheter-directed thrombolysis]] compared with standard treatment alone.
* '''Methods:''' A total of 103 patients with iliofemoral [[DVT]] and symptoms <21 days were randomized to additional CDT or standard treatment alone, in a open multi center, randomized controlled trial. Patients were followed after 6 months with duplex ultrasound and air-plethysmography.
* '''Results:''' Compared with standard treatment alone, patients who underwent CDT had significantly increased ileofemoral potency (RR 28%, 95% CI 9.7%-46.7%, p=0.004). Femoral venous insufficiency was similar in both groups.
* '''Conclusions:''' Additional treatment with CDT in the early course of [[DVT]] is associated with increased iliofemoral vein potency at 6 months.

==Meta-analysis assessing Thromblysis<ref name="pmid15495034">{{cite journal |author=Watson LI, Armon MP |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002783 |year=2004 |pmid=15495034 |doi=10.1002/14651858.CD002783.pub2 |url=}}</ref>==
* '''Objective:''' To determine the efficacy and safety of systemic thrombolysis for treatment of [[DVT]].
* '''Methods:''' A cochrane meta-analysi was conducting including all the randomized controlled trials examining the role of thrombolysis versus anticoagulation for treatment of acute [[DVT]] or calf vein thrombosis.
* '''Results:''' Twelve studies were included in the meta-analysis. Patients who received thrombolysis had a significantly higher rate of clot lysis (RR 0.24, 95% CI 0.07-0.82), lesser incidence of post-thrombotic syndrome (RR 0.66, 95% CI 0.47-0.94), but significantly higher rate of major bleeding complications (RR 1.73, 95% CI 1.04-2.88). Data on occurrence of [[PE]] and recurrent [[DVT]] were inconclusive.
* '''Conclusions:''' Thrombolysis appears to offer advantages in terms of reducing [[post-thrombotic syndrome]] and maintaining venous patency after [[DVT]]. Use of strict eligibility criteria has improved the safety and acceptability of this treatment.

==Use of IVC filters==

==Newer anticoagulants==

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis landmark trials in treatment

2012-05-27T20:08:48Z

Kashish Goel: /* Catheter-directed thrombolysis */

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:56:55Z

Kashish Goel:

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:55:11Z

Kashish Goel: /* Landmark Clinical Trials */

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:53:56Z

Kashish Goel: /* Meta-analysis of Home versus inpatient treatment of DVT{{cite journal |author=Schraibman IG, Milne AA, Royle EM |title=Home versus in-patient treatment for deep vein thrombosis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD0030...

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:53:41Z

Kashish Goel:

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:52:05Z

Kashish Goel: /* Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin */

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:51:07Z

Kashish Goel: /* Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin */

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:49:12Z

Kashish Goel: /* Trials comparing Low-molecular-weight Heparin With subcutaneous unfractionated Heparin */

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:46:17Z

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:45:55Z

Kashish Goel: /* Meta-analysis assessing LMWH dosing */

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:36:22Z

Kashish Goel: /* Trials regarding the use of Fondaprinux */

Deep vein thrombosis landmark trials in treatment

2012-05-27T19:26:38Z

Kashish Goel:

Deep vein thrombosis landmark trials in treatment

2012-05-27T04:35:28Z

Kashish Goel: /* Trials comparing Low-molecular-weight Heparin With intravenous unfractionated Heparin */

Deep vein thrombosis landmark trials in treatment

2012-05-27T04:20:49Z

Kashish Goel: /* Landmark Clinical Trials */

Deep vein thrombosis landmark trials in treatment

2012-05-27T03:58:07Z

Kashish Goel: /* Trial comparing Low-molecular-weight Heparin With Unfractionated Heparin */

Deep vein thrombosis landmark trials in treatment

2012-05-27T03:50:34Z

Kashish Goel:

Deep vein thrombosis landmark trials in treatment

2012-05-27T03:49:43Z

Kashish Goel: /* Trial comparing Low-molecular-weight Heparin With Unfractionated Heparin */

{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]

==Landmark Clinical Trials==
===Trials assessing treatment===
===Trial comparing Low-molecular-weight Heparin With Unfractionated Heparin===
1. Compare subcutaneous [[LMWH]] with unfractionated heparin for treatment of [[VTE]]
* '''Methods:''' A total of 720 patients (including those with [[PE]] and recurrent [[VTE]]) were randomly assigned to subcutaneous [[LMWH]] or fixed-dose unfractionated heparin.
* '''Results:''' Subcutaneous [[LMWH]] and unfractionated heparin groups had similar incidence of recurrent thromboembolic events (4.2% and 3.9%), mortality (3.3% and 3.3%) and major bleeding (0.8% and 1.1%) during 3-months of follow-up.
* '''Conclusions:''' Subcutaneous [[LMWH]] is as effective and safe as [[unfractionated heparin]] for treatment of [[VTE]].

2.
1. Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis. (1990) <ref name="pmid1964751">{{cite journal |author=Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D |title=Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT) |journal=Thromb. Haemost. |volume=64 |issue=4 |pages=506–10 |year=1990 |month=December |pmid=1964751 |doi= |url= |accessdate=2012-05-03}}</ref>
* '''Patient enrollment:''' 119 patients
*''' Purpose:''' To compare subcutaneous low molecular weight heparin with intravenous unfractionated heparin in the treatment of deep vein thrombosis .
*''' Result:''' Repeat phlebography after 5-7 days showed improvement in 34/45 patients (76%) in the Fragmin group and in 30/49 patients (61%) in the SH group and progress in 2/45 (4%) and 3/49 (6%), respectively. The mean Marder scores decreased from 18.7 +/- 12.1 to 15.7 +/- 12.7 in the Fragmin group and from 16.9 +/- 12.0 to 14.4 +/- 11.8 in the SH group (ns). Two patients in the SH group and none in the Fragmin group had major bleedings. After 22 +/- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group. Postthrombotic signs and symptoms were similar in both groups.
*''' Conclusion:''' Two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg.

2. A randomised trial of subcutaneous low molecular weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis. (1991) <ref name="pmid1646490">{{cite journal |author= |title=A randomised trial of subcutaneous low molecular weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis. A collaborative European multicentre study |journal=Thromb. Haemost. |volume=65 |issue=3 |pages=251–6 |year=1991 |month=March |pmid=1646490 |doi= |url= |accessdate=2012-05-02}}</ref>
* '''Patient enrollment:''' 166 patients
*''' Purpose:''' To compare subcutaneous low molecular weight heparin with intravenous unfractionated heparin in the treatment of deep vein thrombosis .
*''' Result:''' Both "therapeutic efficacy" and "intention to-treat" analyses showed that subcutaneous CY 216 in fixed doses based only on body weight was more effective on the Arnesen and Marder phlebographic scores than continuous i.v. standard heparin with daily dose adjustment according to results of coagulation tests. There was no increase in the risks of pulmonary embolism, haemorrhage or clot extension.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]

{{WH}}
{{WS}}

Deep vein thrombosis medical therapy

2012-05-24T13:08:12Z

Kashish Goel: /* Compression stockings */

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel, M.D.]]

{{Deep vein thrombosis}}

==Overview==
An approach to the treatment of [[DVT]] has been described '''[[Deep vein thrombosis treatment algorithm|here]]'''. The primary purpose of treatment is to prevent the following:
* Further clot extension,
* Acute Pulmonary embolism,
* Recurrence of thrombosis,
* Prevention of late complications such as:
** [[Post-thrombotic syndrome]]
** Chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is "treatment of choice" for DVT. An abnormal [[D-dimer]] level at the end of treatment may signal the need for continued treatment, in patients with first unprovoked proximal [[deep-vein thrombosis]].<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref> After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>
===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been evaluated in randomized controlled trials for treatment of [[DVT]]. EINSTEIN-DVT and EINSTEIN-Extension Studies enrolled 3449 patients with DVT and showed that [[rivoraxaban]] was non-inferior to the usual approach (lovenox initially followed by warfarin) in the treatment of [[DVT]]<ref name="pmid21128814">{{cite journal |author=Bauersachs R, Berkowitz SD, Brenner B, ''et al.'' |title=Oral rivaroxaban for symptomatic venous thromboembolism |journal=N. Engl. J. Med. |volume=363 |issue=26 |pages=2499–510 |year=2010 |month=December |pmid=21128814 |doi=10.1056/NEJMoa1007903 |url=}}</ref>. It is not yet approved for treatment of [[DVT]] in US, but FDA will be reviewing this application soon. European Union<refhttp://www.bayer.com/en/news-detail-bayer-group.aspx?newsid=15790</ref> has approved the use of [[rivoraxaban]] for treatment of [[DVT]], however NICE committee in UK<refhttp://www.nelm.nhs.uk/en/NeLM-Area/News/2012---March/13/NICE-issues-preliminary-recommendations-ACD-on-rivaroxaban-for-DVT-treatment-and-the-prevention-of-recurrent-DVT-and-PE-/</ref> has asked for more evidence.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied, beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and were used with 20-30 mm Hg or 30-40 mm Hg pressure gradient. Most trials used knee-high stockings. A cochrane [[meta-analysis]] of [[randomized controlled trials]] reported a reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]], that is, to prevent one case of [[post-thrombotic syndrome]] was 4 to 5 patients.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis medical therapy

2012-05-24T13:06:20Z

Kashish Goel: /* Anticoagulation */

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel, M.D.]]

{{Deep vein thrombosis}}

==Overview==
An approach to the treatment of [[DVT]] has been described '''[[Deep vein thrombosis treatment algorithm|here]]'''. The primary purpose of treatment is to prevent the following:
* Further clot extension,
* Acute Pulmonary embolism,
* Recurrence of thrombosis,
* Prevention of late complications such as:
** [[Post-thrombotic syndrome]]
** Chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is "treatment of choice" for DVT. An abnormal [[D-dimer]] level at the end of treatment may signal the need for continued treatment, in patients with first unprovoked proximal [[deep-vein thrombosis]].<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref> After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>
===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been evaluated in randomized controlled trials for treatment of [[DVT]]. EINSTEIN-DVT and EINSTEIN-Extension Studies enrolled 3449 patients with DVT and showed that [[rivoraxaban]] was non-inferior to the usual approach (lovenox initially followed by warfarin) in the treatment of [[DVT]]<ref name="pmid21128814">{{cite journal |author=Bauersachs R, Berkowitz SD, Brenner B, ''et al.'' |title=Oral rivaroxaban for symptomatic venous thromboembolism |journal=N. Engl. J. Med. |volume=363 |issue=26 |pages=2499–510 |year=2010 |month=December |pmid=21128814 |doi=10.1056/NEJMoa1007903 |url=}}</ref>. It is not yet approved for treatment of [[DVT]] in US, but FDA will be reviewing this application soon. European Union<refhttp://www.bayer.com/en/news-detail-bayer-group.aspx?newsid=15790</ref> has approved the use of [[rivoraxaban]] for treatment of [[DVT]], however NICE committee in UK<refhttp://www.nelm.nhs.uk/en/NeLM-Area/News/2012---March/13/NICE-issues-preliminary-recommendations-ACD-on-rivaroxaban-for-DVT-treatment-and-the-prevention-of-recurrent-DVT-and-PE-/</ref> has asked for more evidence.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A cochrane [[meta-analysis]] of [[randomized controlled trials]] reported a reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]], that is, to prevent one case of [[post-thrombotic syndrome]] was 4 to 5 patients.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis medical therapy

2012-05-23T18:59:28Z

Kashish Goel:

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel, M.D.]]

{{Deep vein thrombosis}}

==Overview==
An approach to the treatment of [[DVT]] has been described '''[[Deep vein thrombosis treatment algorithm|here]]'''. The primary purpose of treatment is to prevent the following:
* Further clot extension,
* Acute Pulmonary embolism,
* Recurrence of thrombosis,
* Prevention of late complications such as:
** [[Post-thrombotic syndrome]]
** Chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of [[low molecular weight heparin]]<ref name="pmid16437432">{{cite journal| author=Hutten BA, Prins MH| title=Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. | journal=Cochrane Database Syst Rev | year= 2006 | volume= | issue= 1 | pages= CD001367 | pmid=16437432 |doi=10.1002/14651858.CD001367.pub2 | pmc= | url= }} </ref>, before they are started on a chronic (3 to 6 month) course of [[warfarin]] (or related [[vitamin K]] inhibitors).

An abnormal [[D-dimer]] level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref>

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:
# Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
# IV unfractionated heparin (UFH), with monitoring.
# SC UFH, with monitoring
# Weight-based SC UFH, without monitoring.
# SC fondaparinux, without monitoring
After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>

===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with [[enoxaparin]] by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A cochrane [[meta-analysis]] of [[randomized controlled trials]] reported a reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]], that is, to prevent one case of [[post-thrombotic syndrome]] was 4 to 5 patients.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis medical therapy

2012-05-23T18:58:53Z

Kashish Goel: /* Compression stockings */

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]

{{Deep vein thrombosis}}

==Overview==
An approach to the treatment of [[DVT]] has been described '''[[Deep vein thrombosis treatment algorithm|here]]'''. The primary purpose of treatment is to prevent the following:
* Further clot extension,
* Acute Pulmonary embolism,
* Recurrence of thrombosis,
* Prevention of late complications such as:
** [[Post-thrombotic syndrome]]
** Chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of [[low molecular weight heparin]]<ref name="pmid16437432">{{cite journal| author=Hutten BA, Prins MH| title=Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. | journal=Cochrane Database Syst Rev | year= 2006 | volume= | issue= 1 | pages= CD001367 | pmid=16437432 |doi=10.1002/14651858.CD001367.pub2 | pmc= | url= }} </ref>, before they are started on a chronic (3 to 6 month) course of [[warfarin]] (or related [[vitamin K]] inhibitors).

An abnormal [[D-dimer]] level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref>

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:
# Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
# IV unfractionated heparin (UFH), with monitoring.
# SC UFH, with monitoring
# Weight-based SC UFH, without monitoring.
# SC fondaparinux, without monitoring
After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>

===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with [[enoxaparin]] by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A cochrane [[meta-analysis]] of [[randomized controlled trials]] reported a reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]], that is, to prevent one case of [[post-thrombotic syndrome]] was 4 to 5 patients.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Template:Preoperative cardiac risk assessment

2012-05-23T17:25:10Z

Kashish Goel:

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[[{{PAGENAME}}#Stepwise approach to preoperative cardiac assessment|Stepwise approach to preoperative cardiac assessment]]
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[[{{PAGENAME}}#Estimated energy requirements for various activities|Estimated energy requirements for various activities]]
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[[{{PAGENAME}}#Cardiac risk stratification for noncardiac surgical procedures|Cardiac risk stratification for noncardiac surgical procedures]]
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[[{{PAGENAME}}#ACC / AHA recommendations for perioperative cardiac assessment|ACC / AHA recommendations for perioperative cardiac assessment]]
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{{PAGENAME}} On the Web
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Preoperative cardiac risk assessment

2012-05-23T17:24:14Z

Kashish Goel:

{{CMG}}; '''Associate Editor-In-Chief:''' [[User: Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]
{{Preoperative cardiac risk assessment}}
==Stepwise approach to preoperative cardiac assessment==
[[Image:Preoperative_Evaluation.jpg|1000px]]

Adapted from Fleisher et al. Circulation. 2009 Nov 24;120(21):e169-276<ref name="pmid19884473">{{cite journal |author=Fleisher LA, Beckman JA, Brown KA,''et al.'' |title=2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American college of cardiology foundation/American heart association task force on practice guidelines |journal=Circulation |volume=120 |issue=21 |pages=e169–276 |year=2009 |month=November |pmid=19884473 |doi=10.1161/CIRCULATIONAHA.109.192690|url=}}</ref>; HR, Heart rate

§,∧ Noninvasive testing is not useful for patients with no clinical risk factors undergoing intermediate-risk or low-risk noncardiac surgery (AHA guidelines Class III, Level of Evidence: C).

¶ '''Clinical risk factors''': Ischemic heart disease, compensated or prior heart failure, diabetes mellitus, renal insufficiency, and cerebrovascular disease

===Active Cardiac conditions*===
'''1. Unstable coronary syndromes'''
* Unstable or severe angina (Canadian Cardiovascular Society class III or IV): May include “stable” angina in patients who are unusually sedentary.
* Recent MI: Greater than 7 days, but less than or equal to 1 month (within 30 days)

'''2. Decompensated HF'''
* NYHA functional class IV
* Worsening or new-onset heart failure

'''3. Significant arrhythmias'''
* High-grade atrioventricular block
* Mobitz II atrioventricular block
* Third-degree atrioventricular heart block
* Symptomatic ventricular arrhythmias
* Supraventricular arrhythmias (including atrial fibrillation) with uncontrolled ventricular rate (HR greater than 100 bpm at rest)
* Symptomatic bradycardia
* Newly recognized ventricular tachycardia

'''4. Severe valvular disease'''
* Severe aortic stenosis (mean pressure gradient >40 mm Hg, aortic valve area <1.0 cm2, or symptomatic)
* Symptomatic mitral stenosis (progressive dyspnea on exertion, exertional presyncope, or heart failure)

===Estimated energy requirements for various activities#===
The '''metabolic equivalent of task (MET)''', or simply '''metabolic equivalent''', is a physiological concept expressing the energy cost of physical activities<ref>Physical activity can be defined as “bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above the basal level”</ref> as multiples of resting [[metabolic rate]] (RMR) and is defined as the ratio of metabolic rate (and therefore the rate of energy consumption) during a specific physical activity to a reference rate of metabolic rate at rest, set by convention to 3.5 ml O2·kg-1·min-1 or equivalently 1 kcal·kg-1· h-1 or 4.184 kJ·kg-1· h-1. By convention 1 MET is considered as the resting metabolic rate obtained during quiet sitting<ref>Ainsworth et al., 1993 </ref><ref> Ainsworth et al., 2000. </ref> . MET values of physical activities range from 0.9 (sleeping) to 18 (running at 17.5 km/h or a 5:31 mile pace).

'''Calculating the weekly energy expended in recreational-time physical activity using METs (Metabolic equivalent task) <ref>Adapted from Compendium of Physical Activities. Ainsworth, BE et al. Medicine and Science in Sports and Exercise. Vol 25, Pg 713 (1993) and Vol 32, S498 (2000).</ref>'''.
{| class="wikitable" border="1"
|-
! Physical Activity
! MET
|-
! Light Intensity Activities
! < 3
|-
| sleeping
| 0.9
|-
| watching television
| 1.0
|-
| writing, desk work, typing
| 1.8
|-
| walking, 1.7 mph (2.7 km/h), level ground, strolling, very slow
| 2.3
|-
| walking, 2.5 mph (4 km/h)
| 2.9
|-
|-
! Moderate Intensity Activities
! 3 to 6
|-
| bicycling, stationary, 50 watts, very light effort
| 3.0
|-
| walking 3.0 mph (4.8 km/h)
| 3.3
|-
| calisthenics, home exercise, light or moderate effort, general
| 3.5
|-
| walking 3.4 mph (5.5 km/h)
| 3.6
|-
| bicycling, <10 mph (16 km/h), leisure, to work or for pleasure
| 4.0
|-
| bicycling, stationary, 100 watts, light effort
| 5.5
|-
! Vigorous Intensity Activities
! > 6
|-
| jogging, general
| 7.0
|-
| calisthenics (e.g. pushups, situps, pullups,jumping jacks), heavy, vigorous effort
| 8.0
|-
| running jogging, in place
| 8.0
|-
| rope jumping
| 10.0
|}

==Cardiac risk stratification for noncardiac surgical procedures==
====High (Reported cardiac risk often greater than 5%)====
* Aortic and other major vascular surgery.
* Peripheral vascular surgery.
* Anticipated prolonged surgical procedures associated with large fluid shifts and/or blood loss.

====Intermediate (Reported cardiac risk generally 1% to 5%)====
* [[Carotid endarterectomy]].
* Head and neck surgery.
* Intraperitoneal and intrathoracic surgery.
* Orthopedic surgery.
* Prostate surgery.

====Low (Reported cardiac risk generally less than 1%)====
* Endoscopic procedures.
* Superficial procedure.
* Cataract surgery.
* Breast surgery.

* Ambulatory surgery

==ACC / AHA recommendations for perioperative cardiac assessment==
This table below contains the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery<ref name="pmid17901357">{{cite journal| author=Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE et al.| title=ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. |journal=Circulation | year= 2007 | volume= 116 | issue= 17 | pages= e418-99 | pmid=17901357 | doi=10.1161/CIRCULATIONAHA.107.185699 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901357 }} </ref>.

{{cquote|
'''Class I'''
#Patients who have a need for emergency noncardiac surgery should proceed to the operating room and continue perioperative surveillance and postoperative risk :stratification and risk factor management. ''(Level of Evidence: C)''
#Patients with active cardiac conditions* should be evaluated and treated per ACC/AHA guidelines and, if appropriate, consider proceeding to the operating room. ''(Level of Evidence: B)''
#Patients undergoing low risk surgery are recommended to proceed to planned surgery.† ''(Level of Evidence: B)''
#Patients with poor (less than 4 METs) or unknown functional capacity and no clinical risk factors should proceed with planned surgery.† ''(Level of Evidence: B)''

'''Class IIa'''
#It is probably recommended that patients with functional capacity greater than or equal to 4 METs without symptoms‡ proceed to planned surgery.§ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for vascular surgery consider testing if it will change management.¶ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for intermediate risk surgery proceed with planned surgery with heart rate control.¶ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 1 or 2 clinical risk factors who are scheduled for vascular or intermediate risk surgery proceed with planned surgery with heart rate control.¶ ''(Level of Evidence: B)''

'''Class IIb'''
#Noninvasive testing might be considered if it will change management for patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for intermediate risk surgery. ''(Level of Evidence: B)''
#Noninvasive testing might be considered if it will change management for patients with poor (less than 4 METs) or unknown functional capacity and 1 or 2 clinical risk factors who are scheduled for vascular or intermediate risk surgery. ''(Level of Evidence: B)''
----
§Noninvasive testing may be considered before surgery in specific
patients with risk factors if it will change management.
Clinical risk factors include ischemic heart disease, compensated or
prior heart failure, diabetes mellitus, renal insufficiency, and cerebrovascular disease.
¶Consider perioperative beta blockade (see Table 12) for populations
in which this has been shown to reduce cardiac morbidity/mortality.}}

==References==
{{reflist|2}}

[[Category:Cardiology]]
[[Category:Surgery]]

{{WikiDoc Help Menu}}
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2012-05-23T16:42:42Z

Kashish Goel:

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2012-05-23T16:41:43Z

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Kashish Goel:

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Preoperative cardiac risk assessment

2012-05-23T16:37:03Z

Kashish Goel: /* Cardiac risk stratification for noncardiac surgical procedures */

{{CMG}}; '''Associate Editor-In-Chief:''' [[User: Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Stepwise approach to preoperative cardiac assessment==
[[Image:Preoperative_Evaluation.jpg|1000px]]

Adapted from Fleisher et al. Circulation. 2009 Nov 24;120(21):e169-276<ref name="pmid19884473">{{cite journal |author=Fleisher LA, Beckman JA, Brown KA,''et al.'' |title=2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American college of cardiology foundation/American heart association task force on practice guidelines |journal=Circulation |volume=120 |issue=21 |pages=e169–276 |year=2009 |month=November |pmid=19884473 |doi=10.1161/CIRCULATIONAHA.109.192690|url=}}</ref>; HR, Heart rate

§,∧ Noninvasive testing is not useful for patients with no clinical risk factors undergoing intermediate-risk or low-risk noncardiac surgery (AHA guidelines Class III, Level of Evidence: C).

¶ '''Clinical risk factors''': Ischemic heart disease, compensated or prior heart failure, diabetes mellitus, renal insufficiency, and cerebrovascular disease

===Active Cardiac conditions*===
'''1. Unstable coronary syndromes'''
* Unstable or severe angina (Canadian Cardiovascular Society class III or IV): May include “stable” angina in patients who are unusually sedentary.
* Recent MI: Greater than 7 days, but less than or equal to 1 month (within 30 days)

'''2. Decompensated HF'''
* NYHA functional class IV
* Worsening or new-onset heart failure

'''3. Significant arrhythmias'''
* High-grade atrioventricular block
* Mobitz II atrioventricular block
* Third-degree atrioventricular heart block
* Symptomatic ventricular arrhythmias
* Supraventricular arrhythmias (including atrial fibrillation) with uncontrolled ventricular rate (HR greater than 100 bpm at rest)
* Symptomatic bradycardia
* Newly recognized ventricular tachycardia

'''4. Severe valvular disease'''
* Severe aortic stenosis (mean pressure gradient >40 mm Hg, aortic valve area <1.0 cm2, or symptomatic)
* Symptomatic mitral stenosis (progressive dyspnea on exertion, exertional presyncope, or heart failure)

===Estimated energy requirements for various activities#===
The '''metabolic equivalent of task (MET)''', or simply '''metabolic equivalent''', is a physiological concept expressing the energy cost of physical activities<ref>Physical activity can be defined as “bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above the basal level”</ref> as multiples of resting [[metabolic rate]] (RMR) and is defined as the ratio of metabolic rate (and therefore the rate of energy consumption) during a specific physical activity to a reference rate of metabolic rate at rest, set by convention to 3.5 ml O2·kg-1·min-1 or equivalently 1 kcal·kg-1· h-1 or 4.184 kJ·kg-1· h-1. By convention 1 MET is considered as the resting metabolic rate obtained during quiet sitting<ref>Ainsworth et al., 1993 </ref><ref> Ainsworth et al., 2000. </ref> . MET values of physical activities range from 0.9 (sleeping) to 18 (running at 17.5 km/h or a 5:31 mile pace).

'''Calculating the weekly energy expended in recreational-time physical activity using METs (Metabolic equivalent task) <ref>Adapted from Compendium of Physical Activities. Ainsworth, BE et al. Medicine and Science in Sports and Exercise. Vol 25, Pg 713 (1993) and Vol 32, S498 (2000).</ref>'''.
{| class="wikitable" border="1"
|-
! Physical Activity
! MET
|-
! Light Intensity Activities
! < 3
|-
| sleeping
| 0.9
|-
| watching television
| 1.0
|-
| writing, desk work, typing
| 1.8
|-
| walking, 1.7 mph (2.7 km/h), level ground, strolling, very slow
| 2.3
|-
| walking, 2.5 mph (4 km/h)
| 2.9
|-
|-
! Moderate Intensity Activities
! 3 to 6
|-
| bicycling, stationary, 50 watts, very light effort
| 3.0
|-
| walking 3.0 mph (4.8 km/h)
| 3.3
|-
| calisthenics, home exercise, light or moderate effort, general
| 3.5
|-
| walking 3.4 mph (5.5 km/h)
| 3.6
|-
| bicycling, <10 mph (16 km/h), leisure, to work or for pleasure
| 4.0
|-
| bicycling, stationary, 100 watts, light effort
| 5.5
|-
! Vigorous Intensity Activities
! > 6
|-
| jogging, general
| 7.0
|-
| calisthenics (e.g. pushups, situps, pullups,jumping jacks), heavy, vigorous effort
| 8.0
|-
| running jogging, in place
| 8.0
|-
| rope jumping
| 10.0
|}

==Cardiac risk stratification for noncardiac surgical procedures==
====High (Reported cardiac risk often greater than 5%)====
* Aortic and other major vascular surgery.
* Peripheral vascular surgery.
* Anticipated prolonged surgical procedures associated with large fluid shifts and/or blood loss.

====Intermediate (Reported cardiac risk generally 1% to 5%)====
* [[Carotid endarterectomy]].
* Head and neck surgery.
* Intraperitoneal and intrathoracic surgery.
* Orthopedic surgery.
* Prostate surgery.

====Low (Reported cardiac risk generally less than 1%)====
* Endoscopic procedures.
* Superficial procedure.
* Cataract surgery.
* Breast surgery.

* Ambulatory surgery

==ACC / AHA recommendations for perioperative cardiac assessment==
This table below contains the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery<ref name="pmid17901357">{{cite journal| author=Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE et al.| title=ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. |journal=Circulation | year= 2007 | volume= 116 | issue= 17 | pages= e418-99 | pmid=17901357 | doi=10.1161/CIRCULATIONAHA.107.185699 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901357 }} </ref>.

{{cquote|
'''Class I'''
#Patients who have a need for emergency noncardiac surgery should proceed to the operating room and continue perioperative surveillance and postoperative risk :stratification and risk factor management. ''(Level of Evidence: C)''
#Patients with active cardiac conditions* should be evaluated and treated per ACC/AHA guidelines and, if appropriate, consider proceeding to the operating room. ''(Level of Evidence: B)''
#Patients undergoing low risk surgery are recommended to proceed to planned surgery.† ''(Level of Evidence: B)''
#Patients with poor (less than 4 METs) or unknown functional capacity and no clinical risk factors should proceed with planned surgery.† ''(Level of Evidence: B)''

'''Class IIa'''
#It is probably recommended that patients with functional capacity greater than or equal to 4 METs without symptoms‡ proceed to planned surgery.§ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for vascular surgery consider testing if it will change management.¶ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for intermediate risk surgery proceed with planned surgery with heart rate control.¶ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 1 or 2 clinical risk factors who are scheduled for vascular or intermediate risk surgery proceed with planned surgery with heart rate control.¶ ''(Level of Evidence: B)''

'''Class IIb'''
#Noninvasive testing might be considered if it will change management for patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for intermediate risk surgery. ''(Level of Evidence: B)''
#Noninvasive testing might be considered if it will change management for patients with poor (less than 4 METs) or unknown functional capacity and 1 or 2 clinical risk factors who are scheduled for vascular or intermediate risk surgery. ''(Level of Evidence: B)''
----
§Noninvasive testing may be considered before surgery in specific
patients with risk factors if it will change management.
Clinical risk factors include ischemic heart disease, compensated or
prior heart failure, diabetes mellitus, renal insufficiency, and cerebrovascular disease.
¶Consider perioperative beta blockade (see Table 12) for populations
in which this has been shown to reduce cardiac morbidity/mortality.}}

==References==
{{reflist|2}}

[[Category:Cardiology]]
[[Category:Surgery]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Preoperative cardiac risk assessment

2012-05-23T16:27:14Z

Kashish Goel:

{{CMG}}; '''Associate Editor-In-Chief:''' [[User: Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@perfuse.org]; [[User:Kashish Goel|Kashish Goel,M.D.]]

==Stepwise approach to preoperative cardiac assessment==
[[Image:Preoperative_Evaluation.jpg|1000px]]

Adapted from Fleisher et al. Circulation. 2009 Nov 24;120(21):e169-276<ref name="pmid19884473">{{cite journal |author=Fleisher LA, Beckman JA, Brown KA,''et al.'' |title=2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American college of cardiology foundation/American heart association task force on practice guidelines |journal=Circulation |volume=120 |issue=21 |pages=e169–276 |year=2009 |month=November |pmid=19884473 |doi=10.1161/CIRCULATIONAHA.109.192690|url=}}</ref>; HR, Heart rate

§,∧ Noninvasive testing is not useful for patients with no clinical risk factors undergoing intermediate-risk or low-risk noncardiac surgery (AHA guidelines Class III, Level of Evidence: C).

¶ '''Clinical risk factors''': Ischemic heart disease, compensated or prior heart failure, diabetes mellitus, renal insufficiency, and cerebrovascular disease

===Active Cardiac conditions*===
'''1. Unstable coronary syndromes'''
* Unstable or severe angina (Canadian Cardiovascular Society class III or IV): May include “stable” angina in patients who are unusually sedentary.
* Recent MI: Greater than 7 days, but less than or equal to 1 month (within 30 days)

'''2. Decompensated HF'''
* NYHA functional class IV
* Worsening or new-onset heart failure

'''3. Significant arrhythmias'''
* High-grade atrioventricular block
* Mobitz II atrioventricular block
* Third-degree atrioventricular heart block
* Symptomatic ventricular arrhythmias
* Supraventricular arrhythmias (including atrial fibrillation) with uncontrolled ventricular rate (HR greater than 100 bpm at rest)
* Symptomatic bradycardia
* Newly recognized ventricular tachycardia

'''4. Severe valvular disease'''
* Severe aortic stenosis (mean pressure gradient >40 mm Hg, aortic valve area <1.0 cm2, or symptomatic)
* Symptomatic mitral stenosis (progressive dyspnea on exertion, exertional presyncope, or heart failure)

===Estimated energy requirements for various activities#===
The '''metabolic equivalent of task (MET)''', or simply '''metabolic equivalent''', is a physiological concept expressing the energy cost of physical activities<ref>Physical activity can be defined as “bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above the basal level”</ref> as multiples of resting [[metabolic rate]] (RMR) and is defined as the ratio of metabolic rate (and therefore the rate of energy consumption) during a specific physical activity to a reference rate of metabolic rate at rest, set by convention to 3.5 ml O2·kg-1·min-1 or equivalently 1 kcal·kg-1· h-1 or 4.184 kJ·kg-1· h-1. By convention 1 MET is considered as the resting metabolic rate obtained during quiet sitting<ref>Ainsworth et al., 1993 </ref><ref> Ainsworth et al., 2000. </ref> . MET values of physical activities range from 0.9 (sleeping) to 18 (running at 17.5 km/h or a 5:31 mile pace).

'''Calculating the weekly energy expended in recreational-time physical activity using METs (Metabolic equivalent task) <ref>Adapted from Compendium of Physical Activities. Ainsworth, BE et al. Medicine and Science in Sports and Exercise. Vol 25, Pg 713 (1993) and Vol 32, S498 (2000).</ref>'''.
{| class="wikitable" border="1"
|-
! Physical Activity
! MET
|-
! Light Intensity Activities
! < 3
|-
| sleeping
| 0.9
|-
| watching television
| 1.0
|-
| writing, desk work, typing
| 1.8
|-
| walking, 1.7 mph (2.7 km/h), level ground, strolling, very slow
| 2.3
|-
| walking, 2.5 mph (4 km/h)
| 2.9
|-
|-
! Moderate Intensity Activities
! 3 to 6
|-
| bicycling, stationary, 50 watts, very light effort
| 3.0
|-
| walking 3.0 mph (4.8 km/h)
| 3.3
|-
| calisthenics, home exercise, light or moderate effort, general
| 3.5
|-
| walking 3.4 mph (5.5 km/h)
| 3.6
|-
| bicycling, <10 mph (16 km/h), leisure, to work or for pleasure
| 4.0
|-
| bicycling, stationary, 100 watts, light effort
| 5.5
|-
! Vigorous Intensity Activities
! > 6
|-
| jogging, general
| 7.0
|-
| calisthenics (e.g. pushups, situps, pullups,jumping jacks), heavy, vigorous effort
| 8.0
|-
| running jogging, in place
| 8.0
|-
| rope jumping
| 10.0
|}

==Cardiac risk stratification for noncardiac surgical procedures==
====High (Reported cardiac risk often greater than 5%)====
*Emergent major operations, particularly in the elderly.
*Aortic and other major vascular surgery.
*Peripheral vascular surgery.
*Anticipated prolonged surgical procedures associated with large fluid shifts and/or blood loss.
====Intermediate (Reported cardiac risk generally less than 5%)====
*[[Carotid endarterectomy]].
*Head and neck surgery.
*Intraperitoneal and intrathoracic surgery.
*Orthopedic surgery.
*Prostate surgery.

====Low (Reported cardiac risk generally less than 1%)====
*Endoscopic procedures.
*Superficial procedure.
*Cataract surgery.
*Breast surgery.

==ACC / AHA recommendations for perioperative cardiac assessment==
This table below contains the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery<ref name="pmid17901357">{{cite journal| author=Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE et al.| title=ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. |journal=Circulation | year= 2007 | volume= 116 | issue= 17 | pages= e418-99 | pmid=17901357 | doi=10.1161/CIRCULATIONAHA.107.185699 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901357 }} </ref>.

{{cquote|
'''Class I'''
#Patients who have a need for emergency noncardiac surgery should proceed to the operating room and continue perioperative surveillance and postoperative risk :stratification and risk factor management. ''(Level of Evidence: C)''
#Patients with active cardiac conditions* should be evaluated and treated per ACC/AHA guidelines and, if appropriate, consider proceeding to the operating room. ''(Level of Evidence: B)''
#Patients undergoing low risk surgery are recommended to proceed to planned surgery.† ''(Level of Evidence: B)''
#Patients with poor (less than 4 METs) or unknown functional capacity and no clinical risk factors should proceed with planned surgery.† ''(Level of Evidence: B)''

'''Class IIa'''
#It is probably recommended that patients with functional capacity greater than or equal to 4 METs without symptoms‡ proceed to planned surgery.§ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for vascular surgery consider testing if it will change management.¶ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for intermediate risk surgery proceed with planned surgery with heart rate control.¶ ''(Level of Evidence: B)''
#It is probably recommended that patients with poor (less than 4 METs) or unknown functional capacity and 1 or 2 clinical risk factors who are scheduled for vascular or intermediate risk surgery proceed with planned surgery with heart rate control.¶ ''(Level of Evidence: B)''

'''Class IIb'''
#Noninvasive testing might be considered if it will change management for patients with poor (less than 4 METs) or unknown functional capacity and 3 or more clinical risk factors who are scheduled for intermediate risk surgery. ''(Level of Evidence: B)''
#Noninvasive testing might be considered if it will change management for patients with poor (less than 4 METs) or unknown functional capacity and 1 or 2 clinical risk factors who are scheduled for vascular or intermediate risk surgery. ''(Level of Evidence: B)''
----
§Noninvasive testing may be considered before surgery in specific
patients with risk factors if it will change management.
Clinical risk factors include ischemic heart disease, compensated or
prior heart failure, diabetes mellitus, renal insufficiency, and cerebrovascular disease.
¶Consider perioperative beta blockade (see Table 12) for populations
in which this has been shown to reduce cardiac morbidity/mortality.}}

==References==
{{reflist|2}}

[[Category:Cardiology]]
[[Category:Surgery]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Deep vein thrombosis medical therapy

2012-05-23T16:21:53Z

Kashish Goel: /* Overview */

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]

{{Deep vein thrombosis}}

==Overview==
An approach to the treatment of [[DVT]] has been described '''[[Deep vein thrombosis treatment algorithm|here]]'''. The primary purpose of treatment is to prevent the following:
* Further clot extension,
* Acute Pulmonary embolism,
* Recurrence of thrombosis,
* Prevention of late complications such as:
** [[Post-thrombotic syndrome]]
** Chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of [[low molecular weight heparin]]<ref name="pmid16437432">{{cite journal| author=Hutten BA, Prins MH| title=Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. | journal=Cochrane Database Syst Rev | year= 2006 | volume= | issue= 1 | pages= CD001367 | pmid=16437432 |doi=10.1002/14651858.CD001367.pub2 | pmc= | url= }} </ref>, before they are started on a chronic (3 to 6 month) course of [[warfarin]] (or related [[vitamin K]] inhibitors).

An abnormal [[D-dimer]] level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref>

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:
# Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
# IV unfractionated heparin (UFH), with monitoring.
# SC UFH, with monitoring
# Weight-based SC UFH, without monitoring.
# SC fondaparinux, without monitoring
After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>

===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with [[enoxaparin]] by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A [[meta-analysis]] of [[randomized controlled trials]] by the [[Cochrane Collaboration]] showed reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]] is quite potent at 4 to 5 patients need to prevent one case of post-phlebitic syndrome.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis medical therapy

2012-05-23T16:21:35Z

Kashish Goel: /* Overview */

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]

{{Deep vein thrombosis}}

==Overview==
An approach to the treatment of [[DVT]] has been described [[Deep vein thrombosis treatment algorithm|here]]. The primary purpose of treatment is to prevent the following:
* Further clot extension,
* Acute Pulmonary embolism,
* Recurrence of thrombosis,
* Prevention of late complications such as:
** [[Post-thrombotic syndrome]]
** Chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of [[low molecular weight heparin]]<ref name="pmid16437432">{{cite journal| author=Hutten BA, Prins MH| title=Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. | journal=Cochrane Database Syst Rev | year= 2006 | volume= | issue= 1 | pages= CD001367 | pmid=16437432 |doi=10.1002/14651858.CD001367.pub2 | pmc= | url= }} </ref>, before they are started on a chronic (3 to 6 month) course of [[warfarin]] (or related [[vitamin K]] inhibitors).

An abnormal [[D-dimer]] level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref>

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:
# Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
# IV unfractionated heparin (UFH), with monitoring.
# SC UFH, with monitoring
# Weight-based SC UFH, without monitoring.
# SC fondaparinux, without monitoring
After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>

===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with [[enoxaparin]] by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A [[meta-analysis]] of [[randomized controlled trials]] by the [[Cochrane Collaboration]] showed reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]] is quite potent at 4 to 5 patients need to prevent one case of post-phlebitic syndrome.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis medical therapy

2012-05-23T16:20:52Z

Kashish Goel:

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]

{{Deep vein thrombosis}}

==Overview==
An approach to the treatment of [[DVT]] has been described [[Deep vein thrombosis treatment algorithm|here]]. The primary purpose of treatment is to prevent the following:
*Further clot extension,
*Acute Pulmonary embolism,
*Recurrence of thrombosis,
*Prevention of late complications such as:
**the [[post-thrombotic syndrome]]
**chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of [[low molecular weight heparin]]<ref name="pmid16437432">{{cite journal| author=Hutten BA, Prins MH| title=Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. | journal=Cochrane Database Syst Rev | year= 2006 | volume= | issue= 1 | pages= CD001367 | pmid=16437432 |doi=10.1002/14651858.CD001367.pub2 | pmc= | url= }} </ref>, before they are started on a chronic (3 to 6 month) course of [[warfarin]] (or related [[vitamin K]] inhibitors).

An abnormal [[D-dimer]] level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref>

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:
# Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
# IV unfractionated heparin (UFH), with monitoring.
# SC UFH, with monitoring
# Weight-based SC UFH, without monitoring.
# SC fondaparinux, without monitoring
After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>

===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with [[enoxaparin]] by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A [[meta-analysis]] of [[randomized controlled trials]] by the [[Cochrane Collaboration]] showed reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]] is quite potent at 4 to 5 patients need to prevent one case of post-phlebitic syndrome.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis

2012-05-23T16:17:49Z

Kashish Goel: /* Treatment */

{{Infobox_Disease |
Name = {{PAGENAME}} |
Image = |
Caption = |
DiseasesDB = 3498 |
ICD10 = {{ICD10|I|80|2|i|80}} |
ICD9 = {{ICD9|453.40}} |
ICDO = |
OMIM = |
MedlinePlus = |
MeshID = D020246 |
}}
{{Deep vein thrombosis}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]; [[User:Kashish Goel|Kashish Goel, M.D.]]

'''For patient information page, click [[{{PAGENAME}} (patient information)|here]]

'''For main page on Venous thrombosis, click [[Venous thrombosis|here]]

'''Synonym:''' DVT

==[[Deep vein thrombosis overview|Overview]]==

==[[Deep vein thrombosis classification scheme|Classification Scheme]]==
'''I''' Upper extremity DVT

'''II''' Lower extremity DVT : [[Deep vein thrombosis classification scheme#Proximal vein thrombosis|Proximal vein thrombosis]] | [[Deep vein thrombosis classification scheme#Distal vein thrombosis|Distal vein thrombosis]]

==[[Deep vein thrombosis pathophysiology|Pathophysiology]]==

==[[Deep vein thrombosis epidemiology and demographics|Epidemiology and Demographics]]==

==[[Deep vein thrombosis risk factors|Risk factors]]==

==[[Deep vein thrombosis screening|Screening]]==

==[[Deep vein thrombosis natural history|Natural History, Complications, and Prognosis]]==

==[[Deep vein thrombosis differential diagnosis|Differentiating Deep vein thrombosis from other Diseases]]==

==Diagnosis==

[[Deep vein thrombosis diagnosis algorithm|Diagnosis Approach]] | [[Pretest probability of DVT|Pretest probability]] | [[Deep vein thrombosis history and symptoms|History & Symptoms]] | [[Deep vein thrombosis physical examination|Physical Examination]] | [[Deep vein thrombosis laboratory tests|D-dimer]] | [[Deep vein thrombosis ultrasound| Ultrasound]] | [[Deep vein thrombosis venography| Venography]] | [[Deep vein thrombosis CT|CT scan venography]] | [[Deep vein thrombosis MRI|MRI]] | [[Deep vein thrombosis other imaging findings|Other Imaging Findings]]

'''[[Deep vein thrombosis diagnosis specific situations|Specific situations]]'''

==Treatment==
* '''[[Deep vein thrombosis treatment algorithm|Treatment Approach]]'''
*'''[[Deep vein thrombosis medical therapy|Medical Therapy]]:'''

:*'''Anticoagulation:''' [[Pulmonary embolism medical therapy#Heparin|Unfractionated Heparin]] | [[Pulmonary embolism medical therapy#Low molecular weight heparin|Low molecular weight heparin]] | [[Pulmonary embolism medical therapy#Factor Xa Inhibitor|Factor Xa inhibitor]] | [[Pulmonary embolism medical therapy#Direct thrombin inhibitors|Direct thrombin inhibitor]] | [[Pulmonary embolism medical therapy#Warfarin|Warfarin]]
:* '''Fibrinolysis:''' [[Deep vein thrombosis medical therapy#Catheter-Directed thrombolysis|Catheter directed thrombolysis]] | [[Deep vein thrombosis medical therapy#Systemic thrombolysis|Systemic thrombolysis]]

*''' [[Deep vein thrombosis surgery|Surgery]]'''
*''' [[Deep vein thrombosis primary prevention|Primary Prevention]]'''

*''' [[Deep vein thrombosis secondary prevention|Secondary Prevention]]'''

==Guidelines==
===ACCP Guidelines===

====[[Guidelines for DVT|Treatment Guidelines]]====

:[[Guidelines for DVT#ACCP Guidelines- Recommendations for initial approach in patients with acute DVT of the leg (DO NOT EDIT)| Recommendations for initial approach for acute DVT of the leg]] | [[Guidelines for DVT#ACCP Guidelines- Recommendations for initial choice of treatment in patients with acute DVT of the leg (DO NOT EDIT)|Recommendations for initial choice of treatment for acute DVT of the leg]] | [[Guidelines for DVT#ACCP Guidelines- Recommendations for duration of anticoagulant therapy (DO NOT EDIT)|Recommendations for duration of anticoagulant therapy]] | [[Guidelines for DVT#ACCP Guidelines- Recommendations for intensity of anticoagulant effect (DO NOT EDIT)|Recommendations for intensity of anticoagulant effect]] | [[Guidelines for DVT#ACCP Guidelines- Recommendations for treatment of isolated distal DVT (DO NOT EDIT)|Recommendations for treatment of isolated distal DVT]] | [[Guidelines for DVT#ACCP Guidelines- Recommendations for treatment of asymptomatic DVT of the leg (DO NOT EDIT)|Recommendations for treatment of asymptomatic DVT of the leg]] | [[Guidelines for DVT#ACCP Guidelines- Recommendations for treatment in special situations (DO NOT EDIT)|Recommendations for treatment in special situations]] | [[Guidelines for DVT#ACCP Guidelines- Recommendations for post-thrombotic syndrome (DO NOT EDIT)|Recommendations for post-thrombotic syndrome]]

====Thromboprophylaxis Guidelines====

:'''[[Deep vein thrombosis guidelines for patients undergoing surgery|Recommendations for patients undergoing non-orthopedic surgery ]]'''

:: [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Nonorthopedic Surgical Patients (DO NOT EDIT)|Recommendations for patients undergoing nonorthopedic surgery ]]: [[Deep vein thrombosis guidelines for patients undergoing surgery#General surgery, GI surgery, Urological surgery and Gynecologic surgery, Bariatric surgery, Vascular surgery, and Plastic and Reconstructive surgery|General surgery, GI surgery, Urological surgery and Gynecologic surgery, Bariatric surgery, Vascular surgery, and Plastic and Reconstructive surgery]] | [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Cardiac Surgery Patients (DO NOT EDIT)|Recommendations for Cardiac Surgery patients]] | [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Thoracic Surgery Patients (DO NOT EDIT)|Recommendations for Thoracic Surgery patients]] | [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Patients undergoing Craniotomy (DO NOT EDIT)|Recommendations for Patients undergoing Craniotomy]] | [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Spinal Surgery Patients (DO NOT EDIT)|Recommendations for Spinal Surgery Patients]] | [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Major Trauma Patients (DO NOT EDIT)|Recommendations for Major Trauma Patients]]

: '''[[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Orthopedic Surgery Patients (DO NOT EDIT)|Recommendations for patients undergoing Orthopedic surgery ]]'''

:: [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Patients Undergoing Major Orthopedic Surgery: THA, TKA, HFS (DO NOT EDIT)|Recommendations for patients undergoing undergoing THA, TKA, HFS ]] | [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in Isolated Lower-Leg Injuries Distal to the Knee (DO NOT EDIT)|Recommendations for Isolated Lower-Leg Injuries Distal to the Knee]] | [[Deep vein thrombosis guidelines for patients undergoing surgery#ACCP Guidelines- Recommendations for Prevention of VTE in patients undergoing Knee Arthroscopy (DO NOT EDIT)|Recommendations for patients undergoing Knee arthroscopy]]

: '''[[Guidelines for prevention of VTE in nonsurgical patients|Recommendations for prevention of VTE in nonsurgical patients]]'''

:: [[Guidelines for prevention of VTE in nonsurgical patients#ACCP Guidelines- Recommendations for Prevention of VTE in Hospitalized Acutely Ill Medical Patients (DO NOT EDIT)|Recommendations for Hospitalized Acutely Ill patients]] | [[Guidelines for prevention of VTE in nonsurgical patients#ACCP Guidelines- Recommendations for Prevention of VTE in Critically Ill Patients (DO NOT EDIT)|Recommendations for Critically Ill patients]] | [[Guidelines for prevention of VTE in nonsurgical patients#ACCP Guidelines- Recommendations for Prevention of VTE in Patients With Cancer in the Outpatient Setting (DO NOT EDIT)|Recommendations for Cancer patients in an outpatient setting]] | [[Guidelines for prevention of VTE in nonsurgical patients#ACCP Guidelines- Recommendations for Prevention of VTE in Chronically Immobilized Outpatients (DO NOT EDIT)|Recommendations for Chronically Immobilized outpatients]] | [[Guidelines for prevention of VTE in nonsurgical patients#ACCP Guidelines- Recommendations for Thromboprophylaxis during Long-Distance Travel|Recommendations for Long-distance Travel]] | [[Guidelines for prevention of VTE in nonsurgical patients#ACCP Guidelines- Recommendations for Thromboprophylaxis to Prevent VTE in Asymptomatic Persons With Thrombophilia|Recommendations for Asymptomatic Persons with Thrombophilia]]

===AHA Guidelines===
* [[Guidelines for DVT#AHA Guidelines for duration of anticoagulant therapy|Guidelines for duration of anticoagulant therapy]]

==[[Deep vein thrombosis landmark trials|Landmark Trials]]==

==References==
{{Reflist|2}}

==See also==
*[[Venogram (medical)]]
*[[Thrombosis]]
*[[Venous thromboembolism]]
*[[Pulmonary embolism]]

{{Circulatory system pathology}}

[[ar:تجلط الوريد العميق]]
[[it:Trombosi venosa profonda]]
[[nl:Diep-veneuze trombose]]
[[pt:Trombose venosa profunda]]
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[[Category:Disease]]
[[Category:Overview complete]]
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[[Category:Up-To-Date]]
[[Category:Up-To-Date cardiology]]

Template:Deep vein thrombosis

2012-05-23T16:17:29Z

Kashish Goel:

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[[Deep vein thrombosis overview|Overview]]
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[[Deep vein thrombosis classification scheme|Classification Scheme]]
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[[Deep vein thrombosis pathophysiology|Pathophysiology]]
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[[Deep vein thrombosis epidemiology and demographics|Epidemiology & Demographics]]
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[[Deep vein thrombosis risk factors|Risk Factors]]
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[[Deep vein thrombosis screening|Screening]]
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[[Deep vein thrombosis differential diagnosis|Differentiating Deep vein thrombosis from other Diseases]]
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Diagnosis
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[[Deep vein thrombosis diagnosis algorithm|Diagnosis Approach]]
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[[Pretest probability of DVT|Pretest Probability]]
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[[Deep vein thrombosis physical examination|Physical Examination]]
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[[Deep vein thrombosis laboratory tests|D-dimer]]
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[[Deep vein thrombosis ultrasound|Ultrasound]]
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[[Deep vein thrombosis venography|Venography]]
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[[Deep vein thrombosis CT|CT scan vengraphy]]
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[[Deep vein thrombosis MRI|MRI]]
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[[Deep vein thrombosis other imaging findings|Other Imaging Findings]]
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Treatment
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[[Deep vein thrombosis treatment algorithm|Treatment Approach]]
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[[Deep vein thrombosis medical therapy|Medical Therapy]]
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[[Deep vein thrombosis surgery|Surgery]]
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[[Deep vein thrombosis primary prevention|Primary Prevention]]
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[[Deep vein thrombosis secondary prevention|Secondary Prevention]]
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[[Guidelines for DVT|Guidelines]]
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[[Deep_vein_thrombosis_guidelines_for_patients_undergoing_surgery|Thromboprophylaxis in Surgical patients]]
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[[Guidelines_for_prevention_of_VTE_in_nonsurgical_patients|Thromboprophylaxis in Nonsurgical patients]]
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[[Deep vein thrombosis landmark trials|Landmark Trials]]
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[[Deep vein thrombosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]]
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[[Deep vein thrombosis future or investigational therapies|Future or Investigational Therapies]]
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{{PAGENAME}} On the Web
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[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&db=pubmed&term={{urlencode:{{#if:{{{1|}}}|{{{1}}}|{{PAGENAME}}}}}} Most recent articles]
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Template:Deep vein thrombosis

2012-05-23T16:17:12Z

Kashish Goel:

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'''Deep vein thrombosis Microchapters
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[[Deep vein thrombosis|Home]]
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[[Deep vein thrombosis (patient information)|Patient Info]]
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[[Deep vein thrombosis overview|Overview]]
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[[Deep vein thrombosis classification scheme|Classification Scheme]]
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[[Deep vein thrombosis pathophysiology|Pathophysiology]]
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[[Deep vein thrombosis epidemiology and demographics|Epidemiology & Demographics]]
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[[Deep vein thrombosis risk factors|Risk Factors]]
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[[Deep vein thrombosis screening|Screening]]
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[[Deep vein thrombosis natural history|Natural History, Complications & Prognosis]]
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[[Deep vein thrombosis differential diagnosis|Differentiating Deep vein thrombosis from other Diseases]]
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Diagnosis
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[[Deep vein thrombosis diagnosis algorithm|Diagnosis Approach]]
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[[Pretest probability of DVT|Pretest Probability]]
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[[Deep vein thrombosis history and symptoms|History & Symptoms]]
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[[Deep vein thrombosis physical examination|Physical Examination]]
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[[Deep vein thrombosis laboratory tests|D-dimer]]
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[[Deep vein thrombosis ultrasound|Ultrasound]]
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[[Deep vein thrombosis venography|Venography]]
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[[Deep vein thrombosis CT|CT scan vengraphy]]
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[[Deep vein thrombosis MRI|MRI]]
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[[Deep vein thrombosis other imaging findings|Other Imaging Findings]]
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[[Deep_vein_thrombosis_diagnosis_specific_situations|Specific situations]]
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Treatment
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[[Deep vein thrombosis treatment algorithm|Treatment Approach]]
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[[Deep vein thrombosis medical therapy|Medical Therapy]]
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[[Deep vein thrombosis surgery|Surgery]]
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[[Deep vein thrombosis primary prevention|Primary Prevention]]
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[[Deep vein thrombosis secondary prevention|Secondary Prevention]]
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[[Guidelines for DVT|Guidelines]]
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[[Deep_vein_thrombosis_guidelines_for_patients_undergoing_surgery|Thromboprophylaxis in Surgical patients]]
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[[Guidelines_for_prevention_of_VTE_in_nonsurgical_patients|Thromboprophylaxis in Nonsurgical patients]]
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[[Deep vein thrombosis landmark trials|Landmark Trials]]
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[[Deep vein thrombosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]]
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[[Deep vein thrombosis future or investigational therapies|Future or Investigational Therapies]]
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Deep vein thrombosis treatment approach

2012-05-23T16:15:00Z

Kashish Goel:

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Kashish Goel|Kashish Goel,M.D.]]; [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]][mailto:urastogi@perfuse.org]

{{Deep vein thrombosis}}

==Overview==
The following algorithm describes the treatment approach to [[DVT]]<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>:

[[Image:DVT_treatment_approach.jpg]]

*Click [[Deep vein thrombosis diagnosis algorithm|here]] for Diagnosis approach.

#Administer parenteral anticoagulants as per [[Guidelines for DVT#ACCP Guidelines- Recommendations for initial choice of treatment in patients with acute DVT of the leg (DO_NOT_EDIT)|ACCP guidelines]] using the recommended [[Deep vein thrombosis medical therapy#Parenteral Anticoagulants|doses]].

¶Comorbid conditions may include history of hemorrhagic CVA, recent bleeding episodes, recent surgery or trauma, severe uncontrolled hypertension, renal failure, potential for non-compliance, suspicion of [[PE]] or pregnancy.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis treatment approach

2012-05-23T16:14:33Z

Kashish Goel:

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Kashish Goel|Kashish Goel,M.D.]]; [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]][mailto:urastogi@perfuse.org]

{{Deep vein thrombosis}}

==Overview==
The following algorithm describes the treatment approach to [[DVT]]<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>:

[[Image:DVT_treatment_approach.jpg]]

*Click [[Deep vein thrombosis diagnosis algorithm|here]] for Diagnosis approach.

#Administer parenteral anticoagulants as per [[Guidelines for DVT#ACCP Guidelines- Recommendations for initial choice of treatment in patients with acute DVT of the leg (DO_NOT_EDIT)|ACCP guidelines]] using the recommended [[Deep vein thrombosis medical therapy#Parenteral Anticoagulants|doses]].

¶Comorbid conditions may include history of hemorrhagic CVA, recent bleeding episodes, recent surgery or trauma, severe uncontrolled hypertension, renal failure, potential for non-compliance, suspicion of [[PE]] or pregnancy.

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

{{WH}}
{{WS}}

Deep vein thrombosis treatment approach

2012-05-23T16:14:08Z

Kashish Goel:

Deep vein thrombosis treatment approach

2012-05-23T16:13:29Z

Kashish Goel:

Deep vein thrombosis medical therapy

2012-05-23T16:11:01Z

Kashish Goel: /* Parenteral Anticoagulants{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinica...

'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]

{{Deep vein thrombosis}}

==Overview==
The primary purpose of treatment is to prevent the following:
*Further clot extension,
*Acute Pulmonary embolism,
*Recurrence of thrombosis,
*Prevention of late complications such as:
**the [[post-thrombotic syndrome]]
**chronic thromboembolic pulmonary hypertension.

==Anticoagulation==
{{main|Anticoagulation}}
[[Anticoagulation]] is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of [[low molecular weight heparin]]<ref name="pmid16437432">{{cite journal| author=Hutten BA, Prins MH| title=Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. | journal=Cochrane Database Syst Rev | year= 2006 | volume= | issue= 1 | pages= CD001367 | pmid=16437432 |doi=10.1002/14651858.CD001367.pub2 | pmc= | url= }} </ref>, before they are started on a chronic (3 to 6 month) course of [[warfarin]] (or related [[vitamin K]] inhibitors).

An abnormal [[D-dimer]] level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref>

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:
# Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
# IV unfractionated heparin (UFH), with monitoring.
# SC UFH, with monitoring
# Weight-based SC UFH, without monitoring.
# SC fondaparinux, without monitoring
After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>

===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>

====[[Heparin]]====
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

====[[LMWH|Low molecular weight heparin]]====
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

====[[Factor Xa Inhibitor]]====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).

====Direct thrombin inhibitors====
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

=====Hirudin=====
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.

=====[[Argatroban]]=====
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of [[heparin-induced thrombocytopenia]].
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

====Warfarin====
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.

====Direct factor Xa inhibitor====
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with [[enoxaparin]] by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

==Thrombolysis==
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

===Systemic thrombolysis===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis

* '''Relative contraindications'''
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race

'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{{cquote|
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).

'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}

==Compression stockings==
Elastic [[compression stockings]] should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A [[meta-analysis]] of [[randomized controlled trials]] by the [[Cochrane Collaboration]] showed reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]] is quite potent at 4 to 5 patients need to prevent one case of post-phlebitic syndrome.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]

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Deep vein thrombosis treatment approach

2012-05-23T16:10:07Z

Kashish Goel:

Deep vein thrombosis treatment approach

2012-05-23T16:03:28Z

Kashish Goel: Created page with "'''Editors-in-Chief:''' C. Michael Gibson, M.S., M.D. '''Associate Editor-In-Chief''': Ujjwal Rastogi, MBBS[mailto:urastogi@perfuse.org]; [[User:K..."