Hemostasis platelet activation

Platelets play a central role in primary hemostasis. They are also important in pathological processes leading to thrombosis. Antiplatelet drugs are primarily directed against platelets and inhibit platelet activation by a number of different mechanisms. They are used for the prevention and treatment of thrombotic processes, especially in the arterial vascular system. 

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. 

The balance of opposing pro- and anti-platelet forces determines the overall hemostatic response. Successful hemostasis is achieved when assorted signal-transduction systems, mediators, white blood cells, and platelet receptors for agonists and adhesion molecules overcome the local resistance against platelet activation to generate... 

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. 

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). 

The intetaction of proteolytically-active a-tfarombin with platelets and other cells of the vasculature, such as endothelial cells and smooth muscle cells, plays a major role in both normal hemostasis and atherosclerosis. Despite extensive studies in numerous laboratories extending back over thirty years, major questions regarding the mechanism of these interactions remain uruesolved. Furthermore, since dirombin can also induce chemotaxis and adhesion of inflammatory cells, and fibroblast mitogenesis, the importance of elucidating the nature of its receptor, or receptors, extends r beyond its role in platelet activation. However, this review will be restricted mainly to considerations of thrombin receptors in human platelets. 

In conclusion, PAF is a unique and potent endogenous lipid mediator which activates platelets. Increases or decreases in PAF levels in vivo can profoundly influence vascular hemostasis. PAF activates multiple signaling pathways in platelets but the molecular properties of platelet PAF receptor and its regulation are poorly understood. Similarly the expression of PAF receptor in megakaryocyte development in normal and disease states would also be a topic of interest in the feture. 

The fatty acid, s )ecifically AA (20 4, functional role in platelet-mediated hemostasis and thrombosis because of its rapid conversion to TxAj upon platelet activation. Over the last few years, we have seen a tremendous interest on AA metabolism within the scientific community. Certainly the interest on PUFAs, has... 

Hemostasis can be impaired by both surgery and general anesthetics (45). Fentanyl, halothane, and enflurane enhance fibrinoljdic activity significantly (46). In addition, there was a raised plasma beta-thromboglobulin concentration (a good indicator of platelet activation) in 61 patients after the use of nitrous oxide, oxygen, and halothane compared with controls (47). 

Brass LF, Manning DR, Shattil DR (1990) GTP-binding proteins and platelet activation. In Progr. Hemostasis Thromb. 10 127-174... 

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