Thrombocytopenia, Heparin-Induced

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

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

  • Can be found at http://www.qxmd.com/calculate-online/hematology/hit-heparin-induced-thrombocytopenia-probability

  • Assesses pretest probability for HIT

  • However, low scores have been shown to be more predictive of excluding HIT, than are intermediate or high scores of predicting its presence

  • When HIT is clinically suspected, a screening PF4-heparin antibody enzyme-linked immunosorbent assay (ELISA) must be performed to establish HIT diagnosis

• 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

Treatment

• 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 ...