THE COAGULATION EXPLOSION

The hemostatic response to vascular damage results in the focal genera tion of alpha-thrombin to produce a fibrin/platelet clot at the site o f vascular injury. This regulated hemostatic response derives from the assembly and activity of enzyme complexes which are localized to surf aces presented by the vascular damage. The product of each enzymatic c omplex provides the serine protease component required for the assembl y and activity of each successive enzyme complex, ultimately leading t o the formation of alpha-thrombin. When one limits attention to those complexes clearly associated with hemostatic or thrombotic risk, the s ignificance of the vitamin-K-dependent enzyme complexes becomes appare nt. Each of these complexes involves a serine protease and a cofactor protein which assemble on a membrane surface in the presence of Ca2(+) . The expression of an active complex involves, in addition to the act ivation of zymogen to an enzyme, the presentation or activation of a c ofactor protein and the provision of the appropriate membrane to suppo rt the reaction. Two plasma cofactors, factor V and factor VIII requir e proteolytic activation, while the cofactors tissue factor and thromb omodulin are membrane-associated proteins, whose presentation is regul ated at the cellular level. The coagulation system that produces alpha -thrombin is an explosion which is regulated by multiple feedback reac tions which amplify the hemostatic response.