Physiology of Hemostasis

Abstract

Disorders of hemostasis and thrombosis arise from the loss of an elegant balance of activation and inhibition among the proteins, the cells in the intravascular compartment, and the parent vessel that carries these participants. Tipping the balance one way or another leads to abnormal bleeding or clotting. Hemostasis, that is, the cessation of bleeding, consists of protein, cellular, and vessel components. The surface of neutrophils, platelets, and endothelial cells are the main loci where hemostasis or thrombosis initiates. The protein components consist of three systems: coagulation, fibrinolysis, and anticoagulant. In physiologic hemostasis when there is a bleeding risk, hemostasis is initiated by tissue factor and factor VIIa. In disease (pathophysiologic states), bleeding cessation can be induced by contact activation of factor XII. Alternatively, in both physiologic and pathophysiologic states, vessel occlusion or thrombosis arises from both expression of tissue factor and factor VIIa or activation of factor XII upon contact with various physiologic or pathophysiologic anionic biologic surfaces. The goal of hemostasis is to generate thrombin in a kinetically fast manner to stop bleeding in a sufficient manner without complete vessel occlusion and downstream tissue ischemia. Two important coagulation protein assemblies, called tenase and prothrombinase, contribute to the rate of thrombin generation that is directly measurable with relatively simple techniques. Three major anticoagulant systems, protein C and S, antithrombin, and tissue factor pathway inhibitor, limit the extent of thrombin formation in vivo. These reactions occur in the intravascular compartment and on or about cell surfaces.