Control of Intravascular Thrombosis

Abstract

The fundamental step in blood coagulation is the formation of insoluble fibrin strands at the site of tissue injury. The cleavage of small polypeptide chains from the soluble parent fibrinogen molecule is sufficient to achieve this transformation. However, this is only the last step in a series of enzymatic reactions that take place during coagulation (Fig. 6.1). It is now recognised that the coagulation cascade is triggered by the interaction of factor VII with tissue factor, a protein released from damaged tissues. The conversion of circulating soluble fibrinogen into insoluble strands of fibrin is achieved by thrombin, which is itself formed by the enzymatic action of a complex of factor X, factor V and calcium on prothrombin (factor II). The initial fibrin clot is relatively unstable as adjacent strands are merely linked by hydrophobic bonds. Factor XIII subsequently stabilises the fibrin by promoting the formation of firm covalent bonds between the fibrin monomers. The coagulation cascade is counterbalanced by natural anticoagulants. Antithrombin inhibits the action of thrombin, whilst proteins C and S destroy coagulation factors V and VIII by cleavage at specific sites.