Mechanism of heparin induced thrombocytopenia (HIT)

Mechanism of HIT. Some individuals produce IgG antibodies directed against heparin complexed with PF4. Platelet Fc receptors bind the antibody-heparin-PF4 immune complex. This leads to platelet activation and microparticle release, which contribute to thrombosis. Thrombocytopenia occurs by two mechanisms: removal of platelets with bound IgG by splenic macrophages and platelet consumption caused by thrombus formation. PF4 can also bind heparan sulfate on vascular endothelial cells; subsequent binding of the pathologic antibody to this PF4-heparan sulfate complex can injure the endothelium, which further promotes thrombosis.