Pathophysiology
Clinical meaning
Heparin-induced thrombocytopenia (HIT) is an immune-mediated prothrombotic disorder caused by IgG antibodies directed against complexes of platelet factor 4 (PF4) and heparin. When heparin binds to PF4 (released from alpha granules of activated platelets), it forms immunogenic PF4-heparin complexes on the platelet surface. In susceptible individuals, IgG antibodies bind these complexes, and the Fc portion of the antibody cross-links FcγIIa receptors on adjacent platelets, causing massive platelet activation, aggregation, and consumption. This paradoxically creates a hypercoagulable state despite thrombocytopenia — HIT is a PROthrombotic disorder, not a bleeding disorder. Activated platelets release procoagulant microparticles and tissue factor, generating thrombin. Endothelial cells and monocytes are also activated, amplifying thrombin generation. HIT typically presents 5-10 days after heparin initiation (or within 24 hours if prior heparin exposure within 100 days). The 4T score is the validated pretest probability tool: Thrombocytopenia (timing and severity of platelet fall), Timing (onset relative to heparin exposure), Thrombosis (new thrombosis or other sequelae), and oTher causes of thrombocytopenia excluded. Score 0-3 = low probability; 4-5 = intermediate; 6-8 = high. Platelet count typically falls 30-50% from baseline...