Heparin-Induced Thrombocytopenia



  • A potentially life-threatening complication of heparin use
    • Platelet count falls 50% or more from baseline.
    • 5–10% daily risk for thromboembolism, amputation, and death
  • 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, platelet count may normalize spontaneously
    • 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.
  • HIT has three different patterns of onset: rapid, typical, and delayed. HIT has three different patterns of onset: rapid, typical, and delayed.
    • Typical pattern is exhibited in 60% of the cases, resulting in fall in platelet decline 5 to 10 days after exposure.
    • Rapid pattern is seen in 30% of the cases with decline in platelet count immediately after exposure to any heparin product
    • Delayed-onset pattern occurs at an average of 9.2 days from initiation of heparin products. It can develop even after cessation of heparin.



  • 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)[B].

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, which acts as a substrate for immunoglobulin (IgG) antibodies. IgG antibodies recognize neoepitopes on PF4 and the resulting complex activates monocytes and platelets, resulting in increased production of thrombin and platelet-fibrin thrombi.
  • 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
    • Postcardiopulmonary bypass (CPB) is the most significant risk factor.
    • Surgical or trauma patients have a greater risk than medical or intensive care unit patients.
  • Bovine UFH > porcine UFH > LMWH; UFH carries a risk 10 times greater than LMWH.
  • Female > male
  • Heparin duration >5 days
  • Therapeutic anticoagulation doses result in a greater reduction in platelet count compared to prophylactic dose.
  • 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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