New concepts in coagulation

The process of blood coagulation is a complex and incompletely understood process. In the last decade or so critical steps have been taken toward better understanding this process. It is now widely agreed that the principal initiating pathway of coagulation is the so-called extrinsic pathway due to the action of tissue factor and Factor VII. Concomitant with this appreciation has come an understanding and elucidation of the roles of tissue factor pathway inhibitor. Although the "intrinsic pathway" is no longer felt to be the initiator of coagulation, recent evidence suggests that Factor XIa may constitute an important amplification pathway of the coagulation system in vivo. Refinement of flow cytometry has enabled the detection of novel platelet antigens on activated platelet surfaces. It is hoped that detection and characterization of these antigens, including adhesion molecules such as P-selectin, will enable further understanding of the platelet's role in pathological coagulation and inflammation. The endothelium is also intricately involved and recent work has determined the importance of endothelial produced factors such as endothelium-derived relaxation factor, endothelin, and thrombomodulin. Finally, with the meteoric rise in molecular genetic technology, specific genetic abnormalities in a number of plasma proteins has been elucidated, with marked implications on the understanding of the coagulation process. For example, the mutation on the gene for Factor V, leading to Arg506 replacement with Gln, produces activated protein C resistance with a concomitant increased risk of venous thrombosis. Thus, significant advances in knowledge of the endothelium, platelets, and plasma factors involved in coagulation have been made and now the challenge of the future is to better elucidate the interactions of these components.