Blood coagulation can be initiated by two pathways: the extrinsic pathway, which is triggered by release of tissue factor from the site of injury, and the intrinsic system, which is stimulated by contact with a negatively charged surface. Following initial triggering, a series of serine proteases are sequentially activated, culminating in the formation of thrombin, the enzyme responsible for the conversion of soluble fibrinogen to the insoluble fibrin clot. Activation of coagulation is tightly regulated. Initiation by tissue factor is inhibited by tissue factor pathway inhibitor. Antithrombin can inactivate many of the serine proteases, including thrombin, by forming stable complexes which are rapidly cleared from the circulation. Protein C and protein S combine to inactivate coagulation factors V and VIII. The deposition of excess fibrin is prevented by the fibrinolytic system which can lyse fibrin into fibrin degradation products. Both genetic and environmental factors can influence the activation of coagulation and may predispose affected individuals to thrombosis.