Pathophysiology of Heparin-Induced Thrombocytopenia (HIT) and new oral anticoagulants. Heparin-induced thrombocytopenia is an immune-mediated complication of exposure to unfractionated or low-molecular-weight heparin. Platelet factor 4 (PF4) released from α-granule of platelet binds to polyanions such as bacteria and heparin, and exposes previously masked epitope, which leads to formation of anti-PF4-IgG antibodies. These antibodies have ability to bind PF4-heparin complexes, and the PF4-heaprin-IgG immune complex activates platelets through binding to FcγRIIa of the platelets, which in turn activates and aggregates platelets. The release of additional PF4 from activated platelets and thrombin activation lead to increased consumption of platelets and eventually thrombocytopenia. The immune complexes also activate monocytes through binding to FcγRI, which can stimulate production of tissue factors from endothelial cells. Dabigatran, a univalent direct thrombin inhibitor, and the FXa inhibitors such as rivaroxaban and apixaban, could serve as an alternative anticoagulants for HIT and thrombosis prophylaxis. Abbreviations: PF4, platelet factor 4; TF, tissue factor; IIa, thrombin; Va, activated factor V; Xa, activated factor X; VIIIa, activated factor VIII; IXa, activated factor IX; AT, antithrombin.