The normal response to vascular injury involves an integrated response among plasma coagulation proteins, platelets, and vascular endothelium. This leads to thrombin generation and formation of a stable haemostatic plug. Exposure of the tissue factor and the extracellular matrix at the site of vascular endothelial injury leads to adherence of platelets to the underlying collagen. This results in activation ofplatelets, releasing thromboxane and adenosine diphos-phate, which attracts and activates additional platelets at the site of vascular injury. In addition, a structural change on the surface of these platelets provides a phospholipid template on which the haemostatic plasma protein cascade may be activated. This ultimately leads to fibrin generation and formation of an integrated platelet-fibrin clot.4
Several intrinsic anti-coagulation mechanisms are present both in the plasma and on the vascular endothelial cell surface to prevent clot propagation beyond the site of vascular injury. Heparan, an endogenous glycosaminoglycan, present on the endothelial surface catalyses the activity of the anti-coagulant anti-thrombin III. A plasma serine protease inhibitor, anti-thrombin III, provides a major mechanism for the elimination of thrombin and other activated coagulation factors from plasma. Tissue plasminogen activator released from the vascular endothelium generates plasmin to degrade fibrin already present. Protein C and Protein S are plasma-derived proteins that modulate coagulation. In addition, thrombomodulin, which is an endothelial cell membrane-bound protein, up regulates the activity of Protein C and alters the pro-coagulant activity of thrombin.4
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