HEMOSTASIS



The arrest of bleeding after blood vessel injury involves a complex interaction among three re­sponding systems: the blood vessel wall, the platelets, and the plasma coagulation proteins. This interaction results in normal hemostasis, but if pathologically exaggerated produces thrombo­sis. While hemostasis is initiated within a few sec­onds after blood vessel injury, it is not completed for minutes to about an hour.

Primary hemostasis involves constriction of the injured vessel, exposure of subendothelial colla­gen, and the adhesion and aggregation of blood platelets on the damaged surface to form a pri­mary hemostatic plug that is completed within 3 to 7 minutes. This process also involves partici­pation of von Willebrand factor (Factor VIII: von Willebrand Factor, Factor VIII: VWF), which me­diates platelet adhesion and the release from platelets of vasoactive materials that augment ag­gregation. Clinical assessment of primary hemo­stasis is made, with the bleeding time, which is a sensitive index of the adequacy of platelet func­tion.

Secondary hemostasis represents the formation of a fibrin clot at the site of the initiating primary hemostatic plug. The surface of activated platelets catalyzes the formation of thrombin by its effi­cient assembly of coagulation factors involved in the prothrombinase complex in the presence of membrane phospholipid and calcium released upon platelet activation. Such localized thrombin activation in turn has several crucial effects. (1) Thrombin catalyzes fibrinogen conversion to fi­brin, the fibrous protein that consolidates the platelet plug and entraps erythrocytes to provide bulk for the permanent clot. (2) Thrombin stim­ulates further platelet activation, prothrombin conversion, platelet release, and thromboxane production. (3) Thrombin activates coagulation Factor XIII, fibrin stabilizing factor, which cova-lently cross-links and stabilizes the fibrin clot. Measurement of secondary hemostasis is made with the whole blood clotting time, which aver­ages 8 to 10 minutes.

The third stage of coagulation is clot retraction, a process in which the loose meshwork of platelet aggregates, fibrin strands, and trapped red cells is formed into a firm clot. This process involves the contraction within individual platelets of the smooth muscle protein, thrornbosthenin, which compresses the clot. This stage may be evaluated in vitro and takes about one hour.