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For further information, see CMDT Part 14-04: Increased Platelet Destruction

Key Features

Essentials of Diagnosis

  • Thrombocytopenia within 5–14 days of exposure to heparin

  • Decline in baseline platelet count of 50% or greater

  • Thrombosis occurs in up to 50% of cases; bleeding is uncommon

General Considerations

  • Affects approximately 3% of patients exposed to unfractionated heparin and 0.6% of patients exposed to low-molecular-weight heparin (LMWH)

  • Results from formation of IgG antibodies to heparin-platelet factor 4 (PF4) complexes; the antibody:heparin-PF4 complex binds to and activates platelets independent of physiologic hemostasis, which leads to thrombocytopenia and thromboses

  • von Willebrand factor has been postulated to play a role in the thrombotic events that take place long after heparin is cleared from the patient's system

Clinical Findings

  • Patients are often asymptomatic

  • Bleeding usually does not occur due to the pro-thrombotic nature of HIT

  • Thrombosis (at any venous or arterial site), however, may be detected in up to 50% of patients, up to 30 days post-diagnosis


  • A presumptive diagnosis of HIT is made when new-onset thrombocytopenia is detected in a patient (typically a hospitalized patient) within 5–14 days of initial exposure to heparin

  • Other presentations (eg, rapid-onset HIT) are less common

  • A decline of ≥ 50% or more from the baseline platelet count is typical

  • The 4T score is a clinical prediction rule

  • If this PF4-heparin antibody ELISA is positive, the diagnosis must be confirmed using a functional assay (such as serotonin release assay)

  • The magnitude of a positive ELISA result correlates with the clinical probability of HIT, but even high ELISA optical density values may be falsely positive; the confirmatory functional assay is essential


  • Initiate as soon as the diagnosis of HIT is suspected, before results of laboratory testing is available

  • Management of HIT (Table 14–5) involves the immediate discontinuation of all forms of heparin

  • If thrombosis has not already been detected, duplex Doppler ultrasound of the lower extremities should be performed to rule out subclinical deep venous thrombosis

  • Despite thrombocytopenia, platelet transfusions are rarely necessary and should be avoided

  • Fondaparinux is an option for some patients

  • Direct thrombin inhibitor (DTI)

    • Argatroban should be administered immediately due to substantial frequency of thrombosis among HIT patients

    • Should be continued until the platelet count has recovered to at least 100,000/mcL (100 × 109/L), at which point treatment with a vitamin K antagonist (warfarin) may be initiated

    • Continue the DTI until therapeutic ...

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