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8. DRUGS AFFECTING PLATELET AGGREGATION AND BLOOD COAGULATION

The main functions of hemostasis are (I) to maintain blood flow in the intact circulatory system which is necessary for normal blood supply to organs and tissues; (II) to stop bleeding in case of injury of a vascular wall.

Arresting of bleeding or hemostasis (from Greek hemo, blood, and stasis, control) is achieved through various mechanisms. Once the vascular wall is damaged, vascular spasm occurs. This is an immediate response to an injury that can arrestbleeding only in case of insignificant damage to small vessels. In general, bleeding is arrested due to thrombus formation impeding blood loss by closing the siteof injury. Such local thrombus formation (platelet or hemostatic plug) is a protective response following an injury. However, in some circumstances, thrombi appear inside blood vessels and occlude their lumen, thus impending normal blood flow. Intravascular thrombus formation may occur in case of pathologic alterations of vascular endothelium, including its damage associated with atherosclerosis, arterial hypertension, or other factors. Thrombus formation may be caused by abnormality of the blood flow (for instance, blood velocity) or congenital /acquired deficiency of some proteins which impede thrombus formation. There are two main processes that lead to thrombus formation: platelet aggregation and blood coagulation (hemocoagulation).

Platelet aggregation is a process whereby platelets adhere to each other to form conglomerates (aggregates) of varying sizes and density. When the vessel wall is injured, this process is initiated by external factors, as well as by biologically active substances contained in platelets. In the place of injury, platelets are directly bound to collagen and other proteins of the subendothelial layer of the vessel wall or are bound by means of Von Willebrand factor (platelet adhesion). This causes activation of platelets (fig. 8.1). As a result of activation, platelets themselves become sources of biologically active substances [serotonin, ade-nosine diphosphate (ADP), and thromboxane A2 (derivative of arachidonic acid)], promoters of platelet aggregation, which are released into the bloodstream. The locally formed thrombin, product of the blood coagulation, induces platelet aggregation as well. Moreover, cate-cholamines, platelet-activating factor, and

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