View source for Pulmonary embolism discharge care and long term treatment

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| [[File:Siren.gif|30px|link=Pulmonary embolism resident survival guide]]|| <br> || <br>
| [[Pulmonary embolism resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{{Pulmonary embolism}}
'''Editor(s)-In-Chief:''' {{ATI}}, [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com]; {{AE}} {{CZ}}; {{Rim}}
==Overview==
While hospital admission is necessary for patients who have a [[pulmonary embolism#Massive Pulmonary Embolism|massive]] or [[pulmonary embolism#Submassive Pulmonary Embolism|submassive pulmonary embolism]] (PE), patients with [[pulmonary embolism#Low-Risk Pulmonary Embolism|low risk PE]] who have no evidence of [[hypotension]], [[RV dysfunction|right ventricular dysfunction]], or myocardial [[necrosis]] can be discharged early on and put on an outpatient treatment regimen.<ref name="pmid20592294">{{cite journal| author=Agnelli G, Becattini C| title=Acute pulmonary embolism. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 3 | pages= 266-74 | pmid=20592294 | doi=10.1056/NEJMra0907731 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20592294  }} </ref> The long term management of [[PE]] depends on whether the episode is the first one or not, whether it is provoked or unprovoked, and on the risk of bleeding of the patient.  Among non cancer patients, the first line therapy for long term outpatient anticoagulation therapy is [[vitamin K antagonist]]s (VKA); whereas the first line treatment among cancer patients is [[low molecular weight heparin]] ([[LMWH]]).

== Discharge Care ==
=== Discharge Criteria ===
* The mortality of [[pulmonary embolism#Low-Risk Pulmonary Embolism|low risk PE]], [[pulmonary embolism#Submassive Pulmonary Embolism|submassive (intermediate risk) PE]], and [[pulmonary embolism#Massive Pulmonary Embolism|massive (high risk) PE ]] increases from <3%, to 3-15%, to >15% respectively.<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September|pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870|accessdate=2011-12-07}}</ref>  Given the elevated rate of mortality in cases of [[pulmonary embolism#Submassive Pulmonary Embolism|submassive]] and [[pulmonary embolism#Massive Pulmonary Embolism|massive]] PE, hospital admission is necessary for patients who are stratified within these categories.<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September|pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870|accessdate=2011-12-07}}</ref>  Hemodynamic stability is not the criteria for discharge. Patients who are hemodynamically stable but have [[RV dysfunction|right ventricular dysfunction]] (stratified as submassive PE), should be admitted. 

* Patients with [[pulmonary embolism#Low-Risk Pulmonary Embolism|low risk PE]] who have no evidence of [[hypotension]], [[RV dysfunction|right ventricular dysfunction]], or myocardial [[necrosis]] can be discharged early on and put on an outpatient treatment regimen.<ref name="pmid20592294">{{cite journal| author=Agnelli G, Becattini C| title=Acute pulmonary embolism. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 3 | pages= 266-74 | pmid=20592294 | doi=10.1056/NEJMra0907731 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20592294  }} </ref>

=== Discharge Medications ===
====Initial Anticoagulation Therapy====
* [[Pulmonary embolism#Low-Risk Pulmonary Embolism|Low risk PE]] patients can have an early discharge and outpatient treatment.  For more details about the choices of treatment, click [[Pulmonary embolism treatment algorithm|here]].

====Long Term Anticoagulation Therapy====
* The long term management of [[PE]] depends on whether the episode is the first one or not, whether it is provoked or unprovoked, and on the risk of [[bleeding]] of the patient.  Among non cancer patients, the first line therapy for long term management of [[PE]] is [[vitamin K antagonist]]s (VKA); whereas the first line treatment among [[cancer]] patients is [[low molecular weight heparin]].  If long term treatment with VKA is decided, VKA should be started at the same day with heparin allowing for at least 5 days of overlap until the [[INR]] is ≥2 for at least 24 hours.  Among patients on extended [[anticoagulation therapy]], the risk vs benefits of the [[anticoagulation therapy]] should be assessed regularly (for example annually).<ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ 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 | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>

Shown below is an algorithm depicting the long term outpatient anticoagulation therapy for patients with PE.<ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ 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 | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>

{{Family tree/start}}
{{familytree | | | | | | | | | | A01 | | | | | | | | A01= <div style="float: left; text-align: left; padding:1em; width:8em">'''Is this the first episode of PE?''' </div>}}
{{familytree | | | | | |,|-|-|-|-|^|-|-|-|-|.| | | | }}
{{familytree | | | | | B01 | | | | | | | | B02 | | | B01= '''YES'''| B02= '''NO'''}}
{{familytree | | | | | |!| | | | | | | | | |!| | | | }}
{{familytree | | | | | C01 | | | | | | | | C02 | | | C01= '''Is PE provoked?'''| C02= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|What is the risk of bleeding?]]'''}}
{{familytree | |,|-|-|-|+|-|-|-|.| | | |,|-|^|-|.| | }}
{{familytree | D01 | | D02 | | D03 | | D04 | | D05 | | D01= <div style="float: left; text-align: left; padding:1em; width:8em">'''Yes, transient reversible risk factor'''</div>| D02= '''Yes, [[cancer]]'''| D03= '''No (unprovoked)'''| D04= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|Low or moderate]]'''| D05= <div style="float: left; text-align: left; padding:1em; width:8em">'''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|High]]'''</div>}}
{{familytree | |!| | | |!| | | |!| | | |!| | | |!| | }}
{{familytree | E01 | | E02 | | E03 | | E04 | | E05 | | E01= <div style="float: left; text-align: left; padding:1em; width:8em">'''Therapy for 3 months'''<br>❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E02= <div style="float: left; text-align: left; padding:1em; width:8em">'''Extended therapy or until cancer is cured'''<br>❑ [[LMWH]] (first line)<br> OR <br> ❑ [[VKA]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E03= <div style="float: left; text-align: left; padding:1em; width:8em">'''Therapy for ≥ 3 months'''<br>❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E04= <div style="float: left; text-align: left; padding:1em; width:8em">'''Extended therapy'''<br>❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>| E05= <div style="float: left; text-align: left; padding:1em; width:8em">'''Therapy for 3 months'''<br>❑ [[VKA]] (first line)<br> OR <br> ❑ [[LMWH]] <br> OR <br> ❑ [[Dabigatran]] <br> OR <br> ❑ [[Rivaroxaban]] </div>}}
{{familytree | | | | | | | | | |!| | | | | | | | | | }}
{{familytree | | | | | | | | | F01 | | | | | | | | | F01= <div style="float: left; text-align: left; padding:1em; width:8em">'''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|Re-assess the risk of bleeding]]'''</div>}}
{{familytree | | | | | | | |,|-|^|-|.| | | | | | | | }}
{{familytree | | | | | | | G01 | | G02 | | | | | | | G01= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|Low or moderate]]'''| G02= '''[[Pulmonary embolism resident survival guide#Assessment of Risk of Bleeding|High]]'''}}
{{familytree | | | | | | | |!| | | |!| | | | | | | | }}
{{familytree | | | | | | | H01 | | H02 | | | | | | | H01= '''Extended therapy'''| H02= <div style="float: left; text-align: left; padding:1em; width:8em">'''Do not extend the therapy beyond the initial 3 months'''</div>}}
{{familytree/end}}


''Note that [[edoxaban]]<ref name="pmid23991658">{{cite journal| author=Hokusai-VTE Investigators. Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S et al.| title=Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. | journal=N Engl J Med | year= 2013 | volume= 369 | issue= 15 | pages= 1406-15 | pmid=23991658 | doi=10.1056/NEJMoa1306638 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23991658  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445714 Review in: Ann Intern Med. 2014 Jan 21;160(2):JC4]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24638182 Review in: Ann Intern Med. 2014 Mar 18;160(6):JC4] </ref> has been evaluated for the treatment of [[VTE]] and is currently seeking approval for this indication.''

* After treatment in the hospital, the patient should continue [[anticoagulation therapy]] for 3 months if the PE is provoked by surgery or a nonsurgical transient risk factor.
* An abnormal [[D-dimer]] level at the end of the treatment course might signal the need for continued treatment with anticoagulation for a first time unprovoked pulmonary embolus.<ref name="pmid17065639">{{cite journal |author=Palareti G, Cosmi B, Legnani C, ''et al'' |title=D-dimer testing to determine the duration of anticoagulation therapy |journal=N. Engl. J. Med. |volume=355 |issue=17 |pages=1780-9 |year=2006 |pmid=17065639 |doi=10.1056/NEJMoa054444}}</ref>
* Long-term treatment is usually recommended with vitamin K antagonists like [[warfarin]], unless [[warfarin]] is contraindicated or in cases of [[cancer]] or [[pregnancy]]..
* The recommended therapeutic INR range for patients with PE is 2.0-3.0.
* Continued warfarin administration needs close monitoring. The patient should have an appointment with the "anticoagulation clinic" before leaving the hospital. 

==== Extended Anticoagulation ====
Extended treatment means extending the anticoagulation therapy beyond the first 3 months. It is recommended in the following scenarios:
* Unprovoked PE: The patient's risk for recurrent PE  should be re-evaluated at 3 months to consider whether or not extended therapy is warranted.
* Active cancer
* Recurrent [[venous thromboembolism]]
* Chronic thrombembolic pulmonary hypertension
* For extended therapy, the continued need for anticoagulation and the risk-benefit ratio should be re-evaluated at periodic intervals (eg, annually).
* Patients with recurrent [[thromboembolic disease]], with or without anticoagulation, should be evaluated for possible [[Thrombophilia#Laboratory testing|thrombophilias]].

==== Specific Circumstances ====
* Malignancy: [[Low molecular weight heparin]] is favored over warfarin based on the results of the CLOT trial.<ref>{{cite journal | author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M|title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med| year=2003 | pages=146-53 | volume=349 | issue=2  | id=PMID 12853587}}</ref> 
* Pregnancy: [[Low molecular weight heparin]] is preferred to avoid the known [[teratogenic]] effects of warfarin.
* Asymptomatic patients who are diagnosed with an incidental PE should be managed with the same criteria as those with symptomatic [[PE]].

==== Newer Anticoagulants ====
* [[Dabigatran]] (direct thrombin inhibitor), [[Rivaroxaban]] (Factor Xa inhibitor), and other drugs in the same classes, provide an alternate option to [[warfarin]]/[[LMWH]] for treatment of [[PE]].
* Advantages include the availability of an oral formulation, no frequent monitoring requirement, a predictable effect profile, and few (known) drug interactions.
* Disadvantages include the currently limited prospective trial data, the theoretical interaction with statins (as they are metabolized by the same CYP3A4 enzyme), and the risk of bleeding.

==References==
{{Reflist|2}}
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[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Intensive care medicine]]