Physiology of hemostasis

Abstract

This chapter describes one of the most remarkable characteristics of blood, its ability to clot. After a brief introduction relating to the history of blood coagulation research, which spans over 100 years, and the evolutionary mechanisms underlying coagulation systems, which indicate that some ancestors of coagulation factors were present over 400 million years ago, we discuss the two principal models of coagulation: cascade versus cell-based. Whereas the former has been the accepted model for over 30 years, the more recent cell-based model appears to be more applicable to in vivo blood coagulation. According to the latter model, platelet activation is a determinant event and can be induced either by thrombin produced as a consequence of the tissue factor/activated factor VII complex on cells bearing tissue factor, or by subendothelial collagen exposure. We then review the role played by endothelium and subendothelium structures in hemostasis and illustrate the relevance of tissue factor. The final sections are dedicated to platelet receptors and signaling pathways and to fibrinolysis, an important regulatory mechanism whose role is to start tissue damage repair, destroy the fibrin clot, restrain the clotting process, and prevent its extension into the vascular system.