Heparin-Induced Thrombocytopenia

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  • A life-threatening complication of heparin use
    • Minimum platelet count falls between 30% and 50% from baseline.
  • Antibody-mediated prothrombotic disorder initiated by heparin administration
  • Unlike other thrombocytopenias, heparin-induced thrombocytopenia (HIT) is an idiosyncratic reaction that results in thrombosis rather than bleeding.
  • Two types: nonimmune heparin-associated thrombocytopenia (previously called HIT type I) and heparin-induced thrombocytopenia/thrombosis (HITT) (immune induced; previously called HIT type II)
    • Nonimmune heparin-associated thrombocytopenia (HIT): more common, onset 1 to 4 days after starting heparin, mild thrombocytopenia (>100,000/mm3), few complications
    • Immune HITT: less common, onset 5 to 14 days after primary exposure to heparin, thrombocytopenia often <100,000/mm3 but usually >20,000/mm3; high risk of thrombosis and mortality


  • 0.1–5% of heparin-treated patients will experience thrombocytopenia, regardless of dose, schedule, or route of administration.
  • 25–50% of these patients will develop HITT (1).

Etiology and Pathophysiology

  • Nonimmune heparin-associated thrombocytopenia: potentially a result of direct platelet membrane binding with heparin
  • HITT: Heparin can cause an increase in the blood concentration of platelet factor 4 (PF4), a chemokine. PF4 will form a complex with heparin.
  • Heparin/PF4 complex can, in turn, stimulate the production of specific antiheparin/PF4 complex antibodies. These antibodies cause platelet activation and a prothrombotic state. Ultimately, this hypercoagulable state leads to thromboembolic complications in many patients.
  • Sources of heparin
  • Heparin flushes (e.g., for arterial lines or heparin locks)
  • Heparin-bonded catheters
  • Unfractionated heparin (UFH)
  • Low-molecular-weight heparin (LMWH) (enoxaparin, dalteparin)

Risk Factors

  • Postsurgical > medical > obstetric
    • Post-cardiopulmonary bypass (CPB) is the most significant risk factor.
  • Bovine UFH > porcine UFH > LMWH
  • Female > male
  • Heparin duration >5 days
  • Rare in pregnant females

General Prevention

  • Inquire about recent heparin exposure and any history of HIT.
  • Use of LMWH (vs. unfractionated), for a shorter duration, can reduce the risk of developing HIT.
  • Properly document past HIT reactions in patient’s medical record. Develop a HIT recognition and treatment protocol.
  • No form of heparin should be administered once the diagnosis of HIT is confirmed.

Commonly Associated Conditions

  • Venous thrombosis: deep venous thrombosis (DVT), pulmonary embolism (PE), adrenal vein thrombosis with hemorrhagic infarction; seen more frequently among medical and postoperative orthopedic surgery patients
  • Arterial thrombosis: myocardial infarction, stroke, mesenteric infarction, limb ischemia; seen more frequently among vascular and cardiac surgery patients
  • Skin lesions (skin necrosis at site of injection)
  • Acute systemic reactions

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