What is the pathophysiology of heparin-induced thrombocytopenia type II?

• A. Formation of antibodies against PF4-heparin complexes that activate platelets, causing thrombosis and thrombocytopenia.
• B. Direct destruction of platelets by heparin.
• C. Vitamin K deficiency triggered by heparin.
• D. Autoimmune destruction of megakaryocytes.

Answer: (A)

HIT type II is an immune-driven process where antibodies form against PF4-heparin complexes. Heparin binds platelet factor 4 released by platelets, creating complexes that the immune system can recognize as foreign. IgG antibodies target these PF4-heparin complexes, and when these antibodies bind, they engage platelet Fc receptors, triggering platelet activation. Activated platelets release procoagulant microparticles and amplify the coagulation cascade, leading to thrombosis, while platelets are consumed, causing thrombocytopenia. The result is a paradoxical combination of low platelet counts and a high risk of clot formation, often several days after starting heparin (and sooner if there was recent prior exposure). This distinct immune-mediated platelet activation differentiates it from simple platelet destruction or vitamin K–related deficiencies.