Platelet in hemostasis

Platelets play an important role in hemostasis and are involved in the pathogenesis of many diseases, such as artherosclerosis and asthma. Moreover, an inadequately controlled aggregation may lead to vascular occlusion. 

Platelets are the formed elements of the blood which participate in hemostasis. Platelets are enucleated, discoid fragments which arise from mature megakaryocytes in the bone marrow. Under normal circumstances, platelets do not adhere to endothelial surfaces of blood vessels. However, platelets can adhere to damaged areas of blood vessels and become activated in such a way that they can also bind fibrinogen. 

We shall first describe the coagulation pathway leading to the formation of fibrin. Then we shall briefly describe some aspects of the involvement of platelets and blood vessel walls in the overall process. This separation of clotting factors and platelets is artificial, since both play intimate and often mutually interdependent roles in hemostasis and thrombosis, but it facifitates description of the overall processes involved. 

Von Willebrand factor (VWF) is a large multimeric glycoprotein with two main functions in hemostasis to aid the platelet adhesion to injured blood vessel walls and to carry and stabilize factor VIII in plasma. Table 64—4 represents three main vWD phenotypes, their frequency, and genetic transmission.17... 

Discuss the role of platelets in various aspects of hemostasis... 

Blood coagulation. The third major step in hemostasis is coagulation, or the formation of a blood clot. This complex process involves a series of reactions that result in formation of a protein fiber meshwork that stabilizes the platelet plug. Three essential steps lead to clotting (see Figure 16.1) ... 

To maintain hemostasis, blood must be retained in the vasculature as fluid. At the same time, blood components must be able to respond rapidly with a clot when a vascular injury occurs. To repair a vascular injury, platelets in blood first adhere as aggregates to the endothelial cells at the affected site and form an initial blood clot. Platelets then stimulate and activate coagulation factors found in plasma to form a more stable fibrin clot. As the injury is resolved and healed, the clot is degraded. Thrombosis is a pathological event wherein a blood clot occludes a blood vessel, resulting in ischemic necrosis of the tissue fed by the blood vessel. Ischemic necrosis involves local anemia and oxygen deprivation. Thrombosis of a coronary artery may lead to myocardial infarction or unstable angina [20]. 

Packham MA, Role of platelets in thrombosis and hemostasis, CanJ Physiol Pharmacol 1994 72 278-284. 

Shattil SJ, Bennett JS. Platelets and their membranes in hemostasis physiology and pathophysiology. Ann Intern Med 1981 94(1) 108 I 18. 

Platelet activation by ADP and adenosine triphosphate (ATP) is a key player in hemostasis and thrombosis, Several receptors are involved, and there are a number of drugs that target these receptors (I). The P2XI receptor is an ATP-gated channel but its role is not yet well defined. 

Denis C, Methia N, Frenette PS et al. (1998) A mouse model of severe von Willebrand disease defects in hemostasis and thrombosis. Proc Natl Acad Sci USA 95 9524-9529 Ni H, Denis CV, Subbarao S et al. (2000) Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest 106 385-392... 

PDI is a noncovalent homodimer with a molecular weight of 57 kDa for each subunit. The protein is generally involved in the formation, reduction and rearrangement of disulfide bridges and plays an important role in platelet function. PDI is localized at the extracellular side of the plasma membrane and is secreted after platelet activation (Chen etal, 1992). In platelets, PDI catalyzes the formation of disulfide-bridged complexes of thrombospondin 1 and thrombin-antithrombin III and is thus involved in hemostasis and wound healing (Milev and Essex, 1999). 

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