Heparin-Induced Thrombocytopenia (HIT)

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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 unfranctionated)
  • 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

Immediate Symptoms

Delayed Symptoms

Differential Diagnosis

Thrombocytopenia

Decreased production

  • Marrow infiltration (tumor or infection)
  • Viral infections (rubella, HIV)
  • Marrow Suppression (commonly chemotherapy or radiation)
  • Congentital thrombocytopenia
    • Fanconi anemia
    • Alport syndrome
    • Bernand Soulier
  • Vitamin B12 and/or folate deficiency

Increased platelet destruction or use

Drug Induced

  • sulfa antibiotics, ETOH, ASA, thiazides/furosemide

Microangiopathic Hemolytic Anemia (MAHA)

Pre-test Probability Scoring[3]

  • 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, low probability (≤5%)
    • 4-5, intermediate prob (~15%)
    • ≥ 6, high prob (~65%)

Evaluation

  • Serotonin release assay (SRA) = gold standard
  • Anti-PF4 plus SRA has combined senativity of 99% [4]
  • 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

  • Discontinue all heparin products
  • 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)
  • Avoid warfarin until platelets >100K-150K

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. 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.