Heparin-Induced Thrombocytopenia Treatment & Management

Updated: Jul 19, 2023
  • Author: Sancar Eke, MD, FASN; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Approach Considerations

If heparin-induced thrombocytopenia (HIT) is suspected, the first step is to discontinue all heparin products immediately and avoid any further exposure. [42] An order to simply "discontinue heparin" may not necessarily prevent heparin exposure, because unfractionated heparin (UFH) is commonly used to flush catheters.

Warfarin may cause microthrombosis in patients with HIT. These patients typically present with an international normalized ratio (INR) greater than 4, which corresponds to severe protein C depletion. Initiation of warfarin should be postponed until substantial platelet recovery. Preferably, warfarin should not be started before the platelet count exceeds 150 × 109/L. [2, 59] If warfarin has already been started, vitamin K should be given. [47]

Platelet transfusions should be avoided in HIT, as they may increase the thrombogenic effect. [59] Guidelines from the American College of Chest Physicians (ACCP) suggest limiting platelet transfusions to patients with severe thrombocytopenia who are experiencing bleeding or undergoing an invasive procedure with a high risk of bleeding. [47]

Patients with HIT are at high risk for thrombotic events and should be treated with alternative anticoagulants, typically a direct thrombin inhibitor (DTI). The US Food and Drug Administration (FDA) has approved the DTI argatroban (Acova) for prophylaxis and treatment of thrombosis in patients with HIT, and as an anticoagulant in patients who are undergoing percutaneous coronary intervention (PCI) and have, or are at risk for, HIT or HIT with thrombosis (HITT). The DTI bivalirudin (Angiomax) is also approved for this indication in PCI (although it has only been studied in patients receiving concomitant aspirin) and it has orphan drug designation for use as an anticoagulant in patients with or at risk of HIT or HITT. The DTI lepirudin was discontinued by the manufacturer in 2012.

The indirect factor Xa inhibitor fondaparinux (Arixtra) is not approved for use in HIT, but some experts consider it an important treatment option, especially in stable, non–critically ill patients. [57, 60, 61]

Another indirect factor Xa inhibitor, danaparoid, is no longer available in the United States but is used in Canada, Europe, and Australia. The ACCP recommends the use of fondaparinux in pregnant patients with HIT if danaparoid is not available, as this agent does not cross the placenta, but otherwise assigns a low evidence rating to treatment of HIT with fondaparinux. [47]

Several novel oral anticoagulants exist (eg, rivaroxaban, dabigatran, apixaban), and preliminary evidence suggests that they may be beneficial for HIT, particularly in cases refractory to standard therapies. [62, 63, 64, 65] However, these agents have not been fully assessed for treatment of patients with HIT and none have FDA approval for use in HIT. [57, 66]

High-dose intravenous immunoglobulin (IVIG) has been used as an adjunct to anticoagulation in patients with HIT. At a usual dose of 1 g/kg for 2 days, IVIG is typically effective in interrupting platelet activation by HIT antibodies and results in a rapid increase in the platelet count. IVIG has also been used to prevent acute HIT when re-exposure to heparin is planned in antibody-positive patients. [67]


Long-term Monitoring

For patients with heparin-induced thrombocytopenia (HIT) who have only isolated thrombocytopenia, therapeutic doses of alternative anticoagulants should be continued until the platelet counts recover to a stable plateau. Because the risk of thrombosis remains high for 2-4 weeks after treatment is initiated, consideration should be given to continuing anticoagulant therapy with an alternative agent or warfarin for up to 4 weeks.

For HIT patients with thrombosis, therapy with an alternative anticoagulant should be followed by a transition to warfarin, but only after platelet counts have recovered to above 150 x 109/L. Oral anticoagulants should be initiated at low doses (eg, ≤ 5 mg/day of warfarin), and an overlap with a direct thrombin inhibitor for at least 5 days should be planned until the international normalized ratio (INR) has been in the therapeutic range for at least 48 hours. Anticoagulation is typically continued for 3 months. [57]

For patients with a past history of HIT who no longer have circulating HIT antibodies, the American College of Chest Physicians suggests that short-term (intraoperative only) heparin can be used for cardiac surgery, but recommends bivalirudin or argatroban for cardiac catheterization or percutaneous coronary intervention. Patients with persistent HIT antibodies who require cardiac surgery should not receive heparin. [57, 47]