The blood coagulation cascade.

Abstract

The biochemistry of blood coagulation has been well defined over the past 50 years. Although much is known about the sequence of the proteolytic cascade and its regulation in the pathway to fibrin generation, many important questions remain unsolved about the mechanism of initiation and the structure of the protein complexes that form during blood coagulation. This article summarizes some of the advances that have been made in this field from the last quarter of 2002 and during 2003. The papers, which vary in rigor and content, have been selected on the basis of their interest and possible contribution to knowledge in this field. Summaries are given of new findings on the source of factor V and the synthesis of factor VIII, the mechanism of tissue factor action in the initiation of blood coagulation, the structure and membrane-binding properties of the protein complexes formed, and regulation of the blood coagulation cascade. Continued progress in this field offers opportunity for understanding the basis of thrombotic diseases and bleeding disorders, with the potential for defining novel targets for therapeutic applications. Some of the conclusions reviewed are conflicting, and further work will be necessary to place the results in the context of what has already been established. The structural biology of the coagulation proteins and understanding of hemostasis and thrombosis in a physiologic context have important implications for future work.