The delicate balance between thrombotic and anti-thromboric activities in maintaining hemostasis while preventing thrombosis is regulated by a variety of cells and by specific cell-mediated mechanisms. The endothelial cell plays an active role in the negative control of thrombus formation. For example, the endothelial cell synthesizes both prostacycline and endothelial cell-derived relaxing factor which inhibit platelet activation and vasoconstriction. Plasminogen activator, which initiates blood clot lysis, is also synthesized and released from endothelium. However, when the vascular endothelium is damaged platelets become activated and undergo a series of changes: adhesion, shape change, secretion of constituents of their storage granule such as ADP, serotonin and arachidonate metabolites, thromboxane A2 (TXA2) and prostaglandin H2, (PGH2), further aggregation to form a hemostatic platelet plug With the changes in platelet membrane during secretion and aggregation, blood coagulation pathway is also activated The generated thrombin is a powerful platelet stimulant as well as having the ability to catalyze fibrin formation, which consolidates the plug with strands of fibrin finishing the hemostasis process.
On the other hand, the same process governing hemostasis is apparently involved in the progression of atherosclerosis, acute coronary artery syndromes such as unstable angina, myocardial infarction, and sudden ischemic death and also in cerebrovascular disease causing stroke Thus, any damage to the vessel wall from atherosclerosis, thermal injury, or infectious agents, etc. is interpreted by this process in the same way as when a vessel is damaged. The resulting platelet activation may result in formation of mural or occlusive thrombi. When the location of the thrombus occurs in the heart or brain, it may be immediately fatal or seriously dehabilitating.
In order to prevent platelet activation in this pathological process, several approaches have been used as antithrombotic therapy, namely, inhibition of von Willibrand factor (vWF)-Glycoprotein (GP)Ib, fibrinogen-GPⅡb a thrombin activation, and thromboxane A2/prostaglandin
H2 (TXA2,/PGH2,) activation Also, for the treatment of thrombosis, several plasminogen activators (PAs) such as tissue-type PA (t-PA) and urokinase-type PA (u-PA, two-chain and single-chain) and streptokinase (SK) have been applied to dissolve the fibrin clot as fibrinolytic therapy
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