Heparin-induced thrombocytopenia resident survival guide: Difference between revisions

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{{familytree | | | | G01 | | | | G01= <div style="float: left; text-align: left; height: 10em; width: 25em; padding:0.5em;">❑ Don't start VKA until the platelet count goes back to normal, after which initiate VKA at low doses <br>❑ When VKA is to be started, overlap it with non heparin anticoagulant for at least 5 days until INR is within the target range<br>❑ If VKAis started when patient is diagnosed with HIT, administer vitamin K<ref name="pmid22315270">{{cite journal| author=Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S et al.| title=Treatment and prevention of heparin-induced thrombocytopenia: 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= e495S-530S | pmid=22315270 | doi=10.1378/chest.11-2303 | pmc=PMC3278058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315270  }} </ref></div>}}
{{familytree | | | | G01 | | | | G01= <div style="float: left; text-align: left; height: 10em; width: 25em; padding:0.5em;">❑ Don't start VKA until the platelet count goes back to normal, after which initiate VKA at low doses <br>❑ When VKA is to be started, overlap it with non heparin anticoagulant for at least 5 days until INR is within the target range<br>❑ If VKAis started when patient is diagnosed with HIT, administer vitamin K<ref name="pmid22315270">{{cite journal| author=Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S et al.| title=Treatment and prevention of heparin-induced thrombocytopenia: 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= e495S-530S | pmid=22315270 | doi=10.1378/chest.11-2303 | pmc=PMC3278058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315270  }} </ref></div>}}
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==Special Considerations==
Shown below is a table summarizing the appropriate choice of anticoagulation therapy in special situations.<ref name="pmid22315270">{{cite journal| author=Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S et al.| title=Treatment and prevention of heparin-induced thrombocytopenia: 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= e495S-530S | pmid=22315270 | doi=10.1378/chest.11-2303 | pmc=PMC3278058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315270  }} </ref>
{| class="wikitable"
|-
| '''Special situations''' || '''Acute HIT or subacute HIT (normal platelets and positive antibodies)''' || '''Past medical history of HIT'''
|-
| '''[[Cardiac surgery]]''' || <u>Urgent cardiac surgery</u>: Use [[bivalirudin]]<br> <u>Non urgent cardiac surgery</u>: Delay the surgery until HIT has resolved and antibodies are negative|| <u>Negative antibodies</u>: Use [[heparin]] (short term) <br> <u>Positive antibodies</u>: Use [[bivalirudin]]
|-
| '''[[PCI]]'''|| Use [[bivalirudin]] or [[argatraban]] ||Use [[bivalirudin]] or [[argatraban]]
|-
| '''[[Dialysis|Renal replacement therapy]]'''||Use [[argatroban]] or [[danaparoid]] || Use regional citrate
|-
| '''[[Pregnancy]]''' ||Use [[danaparoid]]|| -
|-
|}
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<br>
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==Special Considerations==
==4 T's Score==
Shown below is a table summarizing the appropriate choice of anticoagulation therapy in special situations.<ref name="pmid22315270">{{cite journal| author=Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S et al.| title=Treatment and prevention of heparin-induced thrombocytopenia: 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= e495S-530S | pmid=22315270 | doi=10.1378/chest.11-2303 | pmc=PMC3278058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315270  }} </ref>
 
{| class="wikitable"
{| class="wikitable"
!
! Score = 2
! Score = 1
! Score = 0
|-
|-
| '''Special situations''' || '''Acute HIT or subacute HIT (normal platelets and positive antibodies)''' || '''Past medical history of HIT'''
| '''Thrombocytopenia''' <br> Compare the highest platelet count within the sequence of declining platelet counts with the lowest count to determine the % of platelet fall. <br> (Select only 1 option)
|-
| ♦ > 50% platelet fall AND nadir of ≥ 20 AND no surgery within preceding 3 days                                                                 
| '''[[Cardiac surgery]]''' || <u>Urgent cardiac surgery</u>: Use [[bivalirudin]]<br> <u>Non urgent cardiac surgery</u>: Delay the surgery until HIT has resolved and antibodies are negative|| <u>Negative antibodies</u>: Use [[heparin]] (short term) <br> <u>Positive antibodies</u>: Use [[bivalirudin]]
| > 50% platelet fall BUT surgery within preceding 3 days OR <br> ♦ any combination of platelet fall and nadir that does not fit criteria for score 2 or score 0 (eg. 30-50% platelet fall or nadir 10-19)
| < 30% platelet fall <br> any platelet fall with nadir < 10
|-
|-
| '''[[PCI]]'''|| Use [[bivalirudin]] or [[argatraban]] ||Use [[bivalirudin]] or [[argatraban]]
| '''Timing (of platelet count fall or thrombosis)''' <br> Day 0 = first day of most recent heparin exposure <br> (Select only 1 option)
| ♦ platelet fall day 5-10 after start of heparin <br> ♦ platelet fall within 1 day of start of heparin AND exposure to heparin within past 5-30 days
| ♦ consistent with platelet fall days 5-10 but not clear (eg. missing counts) <br> ♦ platelet fall within 1 day of start of heparin AND exposure to heaprin in past 31-100 days <br> ♦ platelet fall after day 10
| ♦ platelet fall ≤ day 4 without exposure to heaprin in pas 100 days
|-
|-
| '''[[Dialysis|Renal replacement therapy]]'''||Use [[argatroban]] or [[danaparoid]] || Use regional citrate
| '''Thrombosis (or other clinical sequelae)''' <br> (Select only 1 option)
| ♦ confirmed new thrombosis (venous or arterial) <br> skin necrosis at injection site <br> ♦ anaphylactoid reaction to IV heparin bolus <br> ♦ adrenal hemorrhage
| ♦ recurrent venous thrombosis in a patient receiving therapeutic anticoagulants <br> ♦ suspected thrombosis (awaiting confirmation with imaging) <br> ♦ erythematous skin lesions at he heparin onjection sites
| ♦ thrombosis suspected
|-
|-
| '''[[Pregnancy]]''' ||Use [[danaparoid]]|| -
| '''Other causes for thrombocytopenia''' <br> (Select only 1 option)
| ♦ no alternative explanation for platelet fall is evident
| Possible other cause is evident: <br> ♦ sepsis without proven microbial source <br> ♦ thrombocytopenia associated with initiation of ventilator <br> ♦ other
| Probable other cause present: <br> ♦ within 72 h of surgery <br> ♦ confirmed bacteremia/fungemia <br> ♦ chemotherapy or radiation within past 20 days <br> ♦ DIC due to non-HIT cause <br> ♦ posttransfusion purpura (PTP) <br> ♦ platelet count < 20 AND given a drug implicated in causing D-ITP <br> ♦ non-necrotizing skin lesions at LMWH injection site <br> ♦ other
|-
|-
|}
|}
<br>


==Do's==
==Do's==

Revision as of 22:41, 2 January 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Karol Gema Hernandez, M.D. [2], Rim Halaby, M.D. [3]

Definition

Heparin induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that predisposes to elevated risks of arterial and venous thromboembolism.

  • Typical-onset HIT: within 5 to 10 days following the initiation of heparin
  • Early-onset HIT: within 24 hours following the initiation of heparin
  • Delayed-onset HIT: up to 3 weeks following the cessation of heparin[1]


  • HITT: Heparin induced thrombocytponia with thrombosis
  • Isolated HIT: Heparin induced thrombocytponia without evidence of thrombosis
  • Subacute HIT: Platelet level is back to normal following an acute episode of HIT; however, HIT antibodies are still positive.[1]

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

Common Causes

Screening for HIT

 
 
Asses the risk of HIT
 
 
 
 
 
 
 
 
 
 
 
 
Patient Population (Minimum of 4-d Exposure)Incidence of HIT, %
Postoperative patients
Heparin, prophylactic dose1-5
Heparin, therapeutic dose1-5
Heparin, flushes0.1-1
LMWH, prophylactic or therapeutic dose0.1-1
Cardiac surgery patients1-3
Medical patients
Patients with cancer1
Heparin, prophylactic or therapeutic dose0.1-1
LMWH, prophylactic or therapeutic dose0.6
Intensive care patients0.4
Heparin, flushes< 0.1
Obstetrics patients <0.1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Risk <1%
 
Risk >1%
 
 
 
 
 
 
 
 
 
 
❑ Do not monitor platelet count
 
❑ Monitor platelet count every 2 or 3 days from day 4 to day 14 (or until heparin is stopped)

Algorithm based on the 2012 ACCP evidence based clinical practice guidelines.[1]

Diagnostic Approach to HIT

 
 
 
Thrombocytopenia
❑ Platelet count <150,000/mm3, OR
❑ >30-50% decrease decrease of platelet from baseline
❑ Recent heparin or LMWH use in the previous 5- 14 days
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Characterize the symptoms (if present):
❑ Arterial thromboembolism
❑ Venous thromboembolism
❑ Unusual manifestations:

- Skin necrosis at SC heparin injection sites
- Transient global amnesia

❑ Absence of petechiae and/or significant bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider alternative diagnoses:
Infection
❑ Medications other than heparin
❑ DIC
Hemodilution
❑ Intravascular devices
Extracorporeal circuits
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suspicion of HIT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low clinical probability
 
 
 
Intermediate/high clinical probability
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unlikely HIT
❑ Consider alternative diagnoses
❑ Continue heparin
 
 
 
❑ Discontinue heparin
❑ Begin alternative anticoagulation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Order anti PF4 antibodies
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderately/strongly positive test
 
Weakly positive test
PLUS
High clinical probability
 
Weakly positive test
PLUS
Intermediatre clinical probability
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Order functional assay
 
 
 
 
 
Unlikely HIT
❑ Consider alternative diagnoses
❑ Continue heparin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive test
Likely HIT
 
Negative test
HIT undetermined
 
 
 
 
 
 
 
 


The most studied functional assays are serotonin release assay (SRA) and Heparin induced platelet activation assay (HIPA).[2]

The diagnostic algorithm is based on "How I treat heparin-induced thrombocytopenia" from Blood (2012).[2]

Treatment of HIT

 
 
 
High suspicion or confirmed HIT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIT with thrombosis
 
 
 
Isolated HIT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Perform a lower extremity U/S to R/O asymptomatic DVT[2]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Presence of asymptomatic DVT
 
No DVT
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Discontinue heparin
❑ Initiate non heparin anticoagulation for 3-6 months:
- Argatroban (can be used in renal insufficiency)
- Lepirudin
- Danaparoid[2]
 
 
 
❑ Discontinue heparin
❑ Initiate non heparin anticoagulation until platelets are back to normal:[2]
- Argatroban (can be used in renal insufficiency)
- Lepirudin
- Danaparoid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Check if patient is/needs to be on VKA
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Don't start VKA until the platelet count goes back to normal, after which initiate VKA at low doses
❑ When VKA is to be started, overlap it with non heparin anticoagulant for at least 5 days until INR is within the target range
❑ If VKAis started when patient is diagnosed with HIT, administer vitamin K[1]
 
 
 



Special Considerations

Shown below is a table summarizing the appropriate choice of anticoagulation therapy in special situations.[1]

Special situations Acute HIT or subacute HIT (normal platelets and positive antibodies) Past medical history of HIT
Cardiac surgery Urgent cardiac surgery: Use bivalirudin
Non urgent cardiac surgery: Delay the surgery until HIT has resolved and antibodies are negative
Negative antibodies: Use heparin (short term)
Positive antibodies: Use bivalirudin
PCI Use bivalirudin or argatraban Use bivalirudin or argatraban
Renal replacement therapy Use argatroban or danaparoid Use regional citrate
Pregnancy Use danaparoid -



Dosages of non Heparin Anticoagulants

Agent Dosage
Direct FXa inhibitors
Argatroban Bolus: None
Continuous infusion:
♦ Normal organ function: 2 μg/kg per minute
♦ Liver dysfunction (total serum bilirubin 1.5 mg/dL), heart failure, postcardiac surgery, anasarca: 0.5-1.2 μg/kg per minute[2]
Lepirudin Bolus:0.2 mg/kg (only for life- or limb-threatening thrombosis)
Continuous infusion:
♦ Cr < 1.0 mg/dL: 0.10 mg/kg per hour
♦ Cr 1.0-1.6 mg/dL: 0.05 mg/kg per hour
♦ Cr 1.6-4.5 mg/dL: 0.01 mg/kg per hour
♦ Cr > 4.5 mg/dL: 0.005 mg/kg per hour[2]
Bivalirudin Bolus: None
Continuous infusion:
♦ Normal organ function: 0.15 mg/kg per hour
♦ Renal or hepatic dysfunction: dose reduction may be appropriate[2]
Indirect FXa inhibitors
Danaparoid Bolus:
♦ < 60 kg: 1500 U
♦ 60-75 kg: 2250 U
♦ 75-90 kg: 3000 U
♦ > 90 kg: 3750 U

Accelerated initial infusion: 400 U/hour X 4 hours, then 300 U/hour X 4 hours
Maintenance infusion:

♦ Normal renal function: 200 U/hour
♦ Renal insufficiency: 150 U/hour[2]


4 T's Score

Score = 2 Score = 1 Score = 0
Thrombocytopenia
Compare the highest platelet count within the sequence of declining platelet counts with the lowest count to determine the % of platelet fall.
(Select only 1 option)
♦ > 50% platelet fall AND nadir of ≥ 20 AND no surgery within preceding 3 days ♦ > 50% platelet fall BUT surgery within preceding 3 days OR
♦ any combination of platelet fall and nadir that does not fit criteria for score 2 or score 0 (eg. 30-50% platelet fall or nadir 10-19)
♦ < 30% platelet fall
any platelet fall with nadir < 10
Timing (of platelet count fall or thrombosis)
Day 0 = first day of most recent heparin exposure
(Select only 1 option)
♦ platelet fall day 5-10 after start of heparin
♦ platelet fall within 1 day of start of heparin AND exposure to heparin within past 5-30 days
♦ consistent with platelet fall days 5-10 but not clear (eg. missing counts)
♦ platelet fall within 1 day of start of heparin AND exposure to heaprin in past 31-100 days
♦ platelet fall after day 10
♦ platelet fall ≤ day 4 without exposure to heaprin in pas 100 days
Thrombosis (or other clinical sequelae)
(Select only 1 option)
♦ confirmed new thrombosis (venous or arterial)
skin necrosis at injection site
♦ anaphylactoid reaction to IV heparin bolus
♦ adrenal hemorrhage
♦ recurrent venous thrombosis in a patient receiving therapeutic anticoagulants
♦ suspected thrombosis (awaiting confirmation with imaging)
♦ erythematous skin lesions at he heparin onjection sites
♦ thrombosis suspected
Other causes for thrombocytopenia
(Select only 1 option)
♦ no alternative explanation for platelet fall is evident Possible other cause is evident:
♦ sepsis without proven microbial source
♦ thrombocytopenia associated with initiation of ventilator
♦ other
Probable other cause present:
♦ within 72 h of surgery
♦ confirmed bacteremia/fungemia
♦ chemotherapy or radiation within past 20 days
♦ DIC due to non-HIT cause
♦ posttransfusion purpura (PTP)
♦ platelet count < 20 AND given a drug implicated in causing D-ITP
♦ non-necrotizing skin lesions at LMWH injection site
♦ other


Do's

  • In case of severe thrombocytopenia among patients with HIT, administer platelet transfusions when the patient is bleeding or when performing procedures associated with an elevated risk of bleeding.[1]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S; et al. (2012). "Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e495S–530S. doi:10.1378/chest.11-2303. PMC 3278058. PMID 22315270.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Cuker A, Cines DB (2012). "How I treat heparin-induced thrombocytopenia". Blood. 119 (10): 2209–18. doi:10.1182/blood-2011-11-376293. PMID 22246036.