Heparin has been used as an anticoagulant medication since the late 1930's and is one of the most prescribed drugs in the North America. However, clinicians recognized that some patients developed a syndrome of immune-mediated thrombocytopenia and thrombosis, which came to be called heparin-induced thrombocytopenia (HIT). HIT occurs when IgG antibodies develop against neoantigens created by multimolecular heparin/platelet factor 4 (PF4) complexes. The antibodies activate platelets, resulting in thrombocytopenia and thrombosis. In HIT, therefore, thrombocytopenia can be considered an indicator of platelet activation and a procoagulant state. Inflammatory cytokines and tissue factor released from activated endothelium and white blood cells may also contribute to the thrombotic tendency.