Which antibodies mediate heparin-induced thrombocytopenia after exposure?

• A. PF4-heparin antibodies (IgG)
• B. Anti-platelet glycoprotein IIb/IIIa antibodies
• C. Anti-Histone antibodies
• D. Anti-DNA antibodies

Answer: (A)

HIT is driven by antibodies against the complex formed by platelet factor 4 (PF4) and heparin, most commonly the IgG class. When heparin is given, PF4 released from platelets binds to heparin, creating PF4–heparin complexes. The immune system frequently makes IgG antibodies against these complexes. The Fc portion of these antibodies then engages FcγIIa receptors on platelets, causing platelet activation and aggregation, release of procoagulant microparticles, further platelet consumption, and a paradoxical prothrombotic state with thrombocytopenia. This specific antibody–antigen interaction explains both the low platelet count and the risk of thrombosis after heparin exposure. The other antibodies listed are associated with different conditions (immune thrombocytopenia not mediated by PF4–heparin, drug-induced lupus, or lupus-related antibodies) and do not explain HIT pathophysiology.