Inborn Defects of the Coagulative System

Over the course of time, blood coagulation has become a highly sophisticated defense mechanism to detect injury to the body and prevent exsanguinations to enhance survival. Surveillance and rapid, localized hemostatic actions of the coagulation system are necessary given the multiple number of breaches to vascular integrity that occur over a lifetime. The coagulation process was understood until a few years ago as a simple “enzyme cascade mechanism.” It involves an orderly and sequential activation of various coagulation factors from an inactive form to an enzymatically active form (theory of enzymatic “cascade” from the mid-1960s). According to this theory, there are two pathways (intrinsic and extrinsic) that converge in a common pathway when factor X is activated. Currently, it is considered that the two pathways of coagulation activation are not separate, but are interconnected. In fact, factors generated in the extrinsic pathway will activate factors and complexes of the intrinsic pathway. The distinction between the two pathways of coagulation activation is still in use but it is important to underline that there are mechanisms of cross-over among the two. There are many diseases that can result from abnormalities of one or more of the three compartments. Among these we consider the inherited deficiencies of coagulation factors. Congenital coagulation defects are hemophilia A, hemophilia B, von Willebrand disease, inherited thrombophilias, and rare coagulation factor deficiencies (deficiencies of fibrinogen, the plasma protease zymogens prothrombin, factors VII, X, XI, and XII, and prekallikrein, the cofactors factor V and high molecular weight kininogen, and the transaminase factor XIII).