Heparin-induced thrombocytopenia

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Background

  • 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 unfrationated or LMWH (10x common in the former)
  • 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]

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.[2]

Type 2 HIT

An immune-mediated process which typically occurs 5-10 days after exposure to heparin complicated by thrombosis. [2]

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

Delayed Symptoms

  • >50% decrease in plt count (median nadir is ~60K; rarely <20K)
  • DVT or PE
  • Cerebral vein or adrenal vein thrombosis
  • Limb arterial occlusion
  • CVA
  • MI
  • Skin necrosis

Immediate 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)

Pre-test Probability Scoring[3]

  • Thrombocytopenia
    • 2 patients: plt > 50% fall AND nadir > 20k
    • 1 pt: pt 30-50% fall OR nadir 10-19k
  • Timing
    • 2 patients: clear onset 5-10 days OR plt 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
  • Thrombosis
    • 2 patients: new thrombosis or skin necrosis at injection sites
    • 1 pt: suspected thrombosis or progressive/recurrent thrombosis
  • Likelihood of other causes
    • 2 patients: none apparent
    • 1 pt: possible
  • Scoring
    • ≤ 3, low probability (≤5%)
    • 4-5, intermediate prob (~15%)
    • ≥ 6, high prob (~65%)

Diagnosis

  • Serotonin release assay (SRA) = gold standard
  • Anti-PF4 plus SRA has combined senativity of 99% [4]
  • Positivity determined by optical density (OD) reported w/ 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

Treatment

  1. Discontinue all heparin products
  2. Do not give platelets (may precipitate thrombosis)
  3. 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)
  4. Avoid warfarin until platelets >100K-150K

Dispostion

  • Admit to medicine with a 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. 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.
  4. Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.