- Heparin-Induced Thrombocytopenia (HIT) is a serious, immune-mediated complication of heparin therapy characterized by a paradoxical association of low platelet counts (thrombocytopenia) with an increased risk of thrombosis rather than bleeding.
- It arises in a subset of patients exposed to unfractionated heparin (UFH) or, less commonly, low-molecular-weight heparin (LMWH).
- The condition is clinically significant because, if unrecognized, it can lead to life-threatening arterial and venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke.
- The underlying pathophysiology of HIT involves the formation of antibodies against complexes of platelet factor 4 (PF4), a protein released from platelet alpha granules, and heparin. These antibodies, predominantly immunoglobulin G (IgG), bind to PF4-heparin complexes and subsequently activate platelets via their Fc receptors. Activated platelets release procoagulant microparticles and promote excessive thrombin generation, creating a highly prothrombotic state despite the presence of thrombocytopenia. Endothelial cells and monocytes may also be activated, further amplifying coagulation and vascular injury.
- Clinically, HIT typically manifests 5–10 days after starting heparin therapy, although earlier onset may occur in patients previously exposed to heparin. The hallmark feature is a platelet count reduction of more than 50% from baseline, even if the absolute platelet count remains above 150,000/µL. Unlike other causes of thrombocytopenia, bleeding is uncommon in HIT; instead, thrombosis is the dominant complication. Both venous and arterial thromboses may occur, with venous events such as deep vein thrombosis and pulmonary embolism being more frequent. Rare but severe complications include skin necrosis at injection sites and limb gangrene.
- Diagnosis of HIT is based on a combination of clinical assessment and laboratory testing. The 4Ts score (thrombocytopenia, timing, thrombosis, and other causes) is a widely used clinical tool to estimate the probability of HIT. Laboratory confirmation involves detecting anti-PF4/heparin antibodies using immunoassays (such as ELISA) and functional platelet activation tests (such as the serotonin release assay), which remain the gold standard. Early recognition is essential, as continued heparin exposure can rapidly worsen the condition.
- Management of HIT requires immediate discontinuation of all heparin products, including heparin flushes and heparin-coated catheters. However, simply stopping heparin is insufficient due to the high risk of thrombosis. Patients must be transitioned to alternative, non-heparin anticoagulants such as direct thrombin inhibitors (argatroban, bivalirudin) or the factor Xa inhibitor fondaparinux. Warfarin should be avoided initially, as it can worsen the prothrombotic state and precipitate venous limb gangrene when started before platelet recovery. In recent years, direct oral anticoagulants (DOACs) have also shown promise in the treatment of HIT.
