Blood coagulation can be initiated by either an extrinsic or an intrinsic pathway, resulting in a cascade of serine protease activation that ultimately leads to the formation of thrombin, which converts soluble fibrinogen to an insoluble fibrin clot. The extrinsic, or tissue factor, pathway is initiated upon vascular injury, when the membrane-bound protein tissue factor (TF) comes into contact with factor VII or VIIa in plasma. The TF-VIIa complex is the strongest known activator of the coagulation cascade, and converts factors IX and X to IXa and Xa, respectively. Factors VII, IX, and X are vitamin-K-dependent proteins produced in the liver. In the intrinsic, or contact, pathway, injury exposes collagen to the bloodstream where is binds to factor XII and activates it to XIIa. Factor XIIa converts prekallikrein to kallikrein and factor XI to XIa. Both the extrinsic and intrinsic pathways result in the activation of factor IX to IXa, which forms the 'tenase' complex with factor VIIIa, calcium and phospholipids. This complex converts factor X to Xa and is important in haemostasis. Factor Xa complexes with factor Va (which functions as a non-enzymatic cofactor), calcium and a phospholipid membrane surface to form what is called the prothrombinase complex, which converts prothrombin to thrombin. Thrombin converts soluble fibrinogen to insoluble fibrin polymer, which is stabilized by cross-linking by coagulation factor XIIIa.

Coagulation References