Steps in blood coagulation and sites of action of new anticoagulants.

Initiation of coagulation is triggered by the factor VIIa/tissue factor complex (VIIa/TF), which activates factor IX (IX) and factor X (X). Activated factor IX (IXa) propagates coagulation by activating factor X in a reaction that utilizes activated factor VIII (VIIIa) as a cofactor. Activated factor X (Xa), with activated factor V (Va) as a cofactor, converts prothrombin (II) to thrombin (IIa). Thrombin then converts fibrinogen to fibrin. Tissue factor pathway inhibitor (TFPI) and nematode anticoagulant peptide (NAPc2) target VIIa/TF, whereas synthetic pentasaccharide and DX-9065a inactivate Xa. Hirudin, bivalirudin, argatroban, and H376/95 inactivate thrombin.