Heparin-induced thrombocytopenia: Difference between revisions

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==Background==
==Background==
*Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
*Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
*Despite the low platelet count, the patient is actually hyper-coagulable and bleeding is unusual.  The activated platelets cause blood clot formation and the platelet count falls because the platelets are bound in clots.
*Can be caused by [[unfractionated heparin]] or [[LMWH]] (10 times more common in unfractionated)
*Can be caused by unfrationated or [[LMWH]] (10x common in the former)
*Occurs in 0.5-5% of patients treated with heparin<ref name="Lovecchio"> Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83</ref>
*Occurs in 0.5-5% of patients treated with heparin<ref name="Lovecchio"> Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83</ref>
*Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month<ref name="Lovecchio"></ref>
*Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month<ref name="Lovecchio"></ref>
*HYPER-coagulable, ''despite'' low platelet count
**activated platelets bound in clot, thus low platelet count
**bleeding is unusual


===Type 1 HIT===
===Type 1 HIT===
Occurs within the first 48 hours after heparin use with an initial drop in platelet count due to direct effect of heparin on platelet activation.  The platelet count normalizes in a few days with continued heparin treatment.<ref name="guidelines hit">Warkentin T. et al. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S</ref>
*Onset within 48h of initiating heparin
*Drop in platelet count due to platelet activation by heparin
*Platelet count usually normalizes in a few days with continued heparin treatment<ref name="guidelines hit">Warkentin T. et al. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S</ref>
===Type 2 HIT===
===Type 2 HIT===
An immune-mediated process which typically occurs 5-10 days after exposure to heparin complicated by thrombosis. <ref name="guidelines hit"></ref>
*Immune-mediated process
*Onset typically 5-10 days after exposure to heparin
*Complicated by thrombosis<ref name="guidelines hit"></ref>


==Clinical Features==
==Clinical Features==
;Symptoms usually begin 5-10 days after initiation of heparin or can begin within hours if there are already preexisting circulating antibody from prior sensitization
[[File:PMC1865550 1752-1947-1-13-1.png|thumb|Gangrenous right hand and left foot in a patient with antibody-confirmed HIT.]]
[[File:PMC4763479 cvja-26-e13-g003.png|thumb|Ischaemic changes in the right hand (A), right foot (B), and left food (C) from HIT.]]
[[File:PMC3555208 hr-2012-4-e20-g002.png|thumb|Lower extremity gangrene secondary to both arterial and venous thrombosis.]]
*The 4 T's: (formal scoring system below)
**[[Thrombocytopenia|'''T'''hrombocytopenia]]
**'''T'''iming (5-14d)
**[[thromboembolism|'''T'''hrombosis]]
**No o'''T'''her cause
 
===Immediate Symptoms===
*Flushing
*[[Tachycardia]]
*[[Hypotension]]
*[[Dyspnea]]


===Delayed Symptoms===
===Delayed Symptoms===
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*[[DVT]] or [[PE]]
*[[DVT]] or [[PE]]
*Cerebral vein or adrenal vein thrombosis
*Cerebral vein or adrenal vein thrombosis
*Limb arterial occlusion
*[[Acute arterial ischemia|Limb arterial occlusion]]
*[[CVA]]
*[[CVA]]
*[[MI]]
*[[MI]]
*Skin necrosis
*Skin necrosis
===Immediate Symptoms===
*Flushing
*Tachycardia
*[[Hypotension]]
*[[Dyspnea]]


==Differential Diagnosis==
==Differential Diagnosis==
{{Thrombocytopenia}}
{{Thrombocytopenia}}
{{Hemolytic anemia DDX}}


{{Hemolytic anemia DDX}}
==Evaluation==
*Serotonin release assay (SRA) = gold standard
*Anti-PF4 plus SRA has combined sensitivity of 99% <ref>Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.</ref>
*Positivity determined by optical density (OD) reported with assay (same concept as a titer)
**OD <1 = <5% chance of HIT
**OD 1.4 = 50% chance of HIT
**OD >2 = 90% chance of HIT


==Pre-test Probability Scoring<ref>Janz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.</ref>==
===Pre-test Probability Scoring (The 4 T Score)<ref>Janz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.</ref>===
*Thrombocytopenia
*Thrombocytopenia
**2 patients: platelets > 50% fall AND nadir > 20k
**2 points: platelets > 50% fall AND nadir > 20k
**1 pt: patient 30-50% fall OR nadir 10-19k
**1 points: patient 30-50% fall OR nadir 10-19k
*Timing
*Timing
**2 patients: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days
**2 points: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days
**1 pt: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
**1 point: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
*Thrombosis
*Thrombosis
**2 patients: new thrombosis or skin necrosis at injection sites
**2 points: new thrombosis or skin necrosis at injection sites
**1 pt: suspected thrombosis or progressive/recurrent thrombosis
**1 point: suspected thrombosis or progressive/recurrent thrombosis
*Likelihood of other causes
*Likelihood of other causes
**2 patients: none apparent
**2 points: none apparent
**1 pt: possible
**1 point: possible
*Scoring
*Scoring
**≤ 3, low probability (≤5%)
**≤3 is low risk and do not require further testing or heparin discontinuation
**4-5, intermediate prob (~15%)
**≥4 should have serologic testing performed, heparin discontinued, and alternative anticoagulation started
**≥ 6, high prob (~65%)
 
==Diagnosis==
*Serotonin release assay (SRA) = gold standard
*Anti-PF4 plus SRA has combined senativity of 99% <ref>
Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.</ref>
*Positivity determined by optical density (OD) reported with assay (same concept as a titer)
**OD <1 = <5% chance of HIT
**OD 1.4 = 50% chance of HIT
**OD >2 = 90% chance of HIT


==Management==
==Management==
#Discontinue all [[heparin]] products  
*Discontinue all [[heparin]] products <ref>Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, Linkins LA, Rodner SB, Selleng S, Warkentin TE, Wex A, Mustafa RA, Morgan RL, Santesso N. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-3392. doi: 10.1182/bloodadvances.2018024489. PMID: 30482768; PMCID: PMC6258919.</ref>
#Do not give [[platelets]] (may precipitate thrombosis)
*Do '''not''' give [[platelets]] (may precipitate thrombosis)
#Start anticoagulation with no heparin based compound such as a direct thrombin inhibitor [lepirudin (unless renal failure), argatroban (unless hepatobiliary disease), bivalirudin] or direct Xa inhibitor (fondaparinux, danaparoid)
*Start anticoagulation with no heparin based compound such as a direct thrombin inhibitor: [lepirudin (unless renal failure), [[argatroban]] (unless hepatobiliary disease), [[bivalirudin]]] or direct Xa inhibitor ([[fondaparinux]], danaparoid)
#''Avoid [[warfarin]] until platelets >100K-150K''
**4T Score ≥4 with/without thrombosis and average bleeding risk should receive '''therapeutic''' dose
**4T Score ≥4 with/without thrombosis and high bleeding risk should receive '''prophylactic''' dose
*''Avoid [[warfarin]] until platelets >100K-150K''
**Those already on warfarin should receive vitamin K to restore protein C & S levels


==Dispostion==
==Disposition==
*Admit to medicine with a hematology consult
*Admit (with hematology consult)


==See Also==
==See Also==
*[[Unfractionated Heparin]]
*[[Unfractionated heparin]]
*[[Low Molecular Weight Heparin]]
*[[Low molecular weight heparin]]
*[[Coagulopathy (Main)]]
*[[Coagulopathy (main)]]
*[[Hirudins]]


==References==
==References==

Latest revision as of 21:34, 7 June 2023

Background

  • Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
  • Can be caused by unfractionated heparin or LMWH (10 times more common in unfractionated)
  • Occurs in 0.5-5% of patients treated with heparin[1]
  • Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month[1]
  • HYPER-coagulable, despite low platelet count
    • activated platelets bound in clot, thus low platelet count
    • bleeding is unusual

Type 1 HIT

  • Onset within 48h of initiating heparin
  • Drop in platelet count due to platelet activation by heparin
  • Platelet count usually normalizes in a few days with continued heparin treatment[2]

Type 2 HIT

  • Immune-mediated process
  • Onset typically 5-10 days after exposure to heparin
  • Complicated by thrombosis[2]

Clinical Features

Gangrenous right hand and left foot in a patient with antibody-confirmed HIT.
Ischaemic changes in the right hand (A), right foot (B), and left food (C) from HIT.
Lower extremity gangrene secondary to both arterial and venous thrombosis.

Immediate Symptoms

Delayed Symptoms

Differential Diagnosis

Thrombocytopenia

Decreased production

Increased platelet destruction or use

Drug Induced

Comparison by Etiology

ITP TTP HUS HIT DIC
↓ PLT Yes Yes Yes Yes Yes
↑PT/INR No No No +/- Yes
MAHA No Yes Yes No Yes
↓ Fibrinogen No No No No Yes
Ok to give PLT Yes No No No Yes

Microangiopathic Hemolytic Anemia (MAHA)

Evaluation

  • Serotonin release assay (SRA) = gold standard
  • Anti-PF4 plus SRA has combined sensitivity of 99% [3]
  • Positivity determined by optical density (OD) reported with assay (same concept as a titer)
    • OD <1 = <5% chance of HIT
    • OD 1.4 = 50% chance of HIT
    • OD >2 = 90% chance of HIT

Pre-test Probability Scoring (The 4 T Score)[4]

  • Thrombocytopenia
    • 2 points: platelets > 50% fall AND nadir > 20k
    • 1 points: patient 30-50% fall OR nadir 10-19k
  • Timing
    • 2 points: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days
    • 1 point: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
  • Thrombosis
    • 2 points: new thrombosis or skin necrosis at injection sites
    • 1 point: suspected thrombosis or progressive/recurrent thrombosis
  • Likelihood of other causes
    • 2 points: none apparent
    • 1 point: possible
  • Scoring
    • ≤3 is low risk and do not require further testing or heparin discontinuation
    • ≥4 should have serologic testing performed, heparin discontinued, and alternative anticoagulation started

Management

  • Discontinue all heparin products [5]
  • Do not give platelets (may precipitate thrombosis)
  • Start anticoagulation with no heparin based compound such as a direct thrombin inhibitor: [lepirudin (unless renal failure), argatroban (unless hepatobiliary disease), bivalirudin] or direct Xa inhibitor (fondaparinux, danaparoid)
    • 4T Score ≥4 with/without thrombosis and average bleeding risk should receive therapeutic dose
    • 4T Score ≥4 with/without thrombosis and high bleeding risk should receive prophylactic dose
  • Avoid warfarin until platelets >100K-150K
    • Those already on warfarin should receive vitamin K to restore protein C & S levels

Disposition

  • Admit (with hematology consult)

See Also

References

  1. ↑ 1.0 1.1 Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83
  2. ↑ 2.0 2.1 Warkentin T. et al. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S
  3. ↑ Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.
  4. ↑ Janz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.
  5. ↑ Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, Linkins LA, Rodner SB, Selleng S, Warkentin TE, Wex A, Mustafa RA, Morgan RL, Santesso N. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-3392. doi: 10.1182/bloodadvances.2018024489. PMID: 30482768; PMCID: PMC6258919.
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