Interruption of Thrombosis and Hemostasis by Anti-Platelet Agents

Abstract

Blood platelets play a fundamental role in hemostasis and thrombosis. The physiological role of platelets is to preserve the integrity of the cardiovascular system such that upon injury platelets are activated and serve to interrupt a potentially deleterious situation (i.e., hemorrhage). However, platelets are also involved in the pathophysiology of thrombosis in which the normal repair process is grossly exacerbated, resulting in interruption of blood flow to vital tissues. Thus, a critical balance exists between the normal function of blood platelets to preserve tissue function and a pathophysiological function in which tissue is damaged due to thrombosis and subsequent ischemia. Numerous anti-platelet agents have been developed in an attempt to interrupt the thrombotic process without severely compromising the hemostatic state of patients. This article will be devoted to a discussion of a commonly utilized anti-thrombotic agent, aspirin, as well as a class of newer, possibly more effective anti-thrombotic agents referred to collectively as fibrinogen receptor antagonists.

Should More Patients Continue Aspirin Therapy Perioperatively?

“…When endothelial damage occurs, however, the hemostatic process (including platelet aggregation and activation) is initiated to stop bleeding. If this process becomes exaggerated, excess thrombosis can lead to unwanted vascular occlusion 27 and adverse cardiovascular events. 2 Aspirin irreversibly inactivates COX through acetylation of the amino acid serine, 8 with a 170-fold affinity for COX-1 over COX-2.…”

Impaired antiplatelet effects of aspirin associated with hypoxia and ATP release from erythrocytes. Studies in a system with flowing human blood

“…Inhibition of platelet function is one of the important aims of antithrombotic therapy [1,2]. The importance of arachidonic acid metabolites in the regulation of platelet function through the cyclo-oxygenase (COX) pathway is well known [3].…”

“…The remarkable antiplatelet action of ASA observed in aggregation tests does not agree with the relatively moderate effects observed in clinical practice. Data from clinical trials indicate that ASA therapy would prevent 35-40 thrombotic events per 1000 patients treated when they have a previous history, but only four events per 1000 subjects when ASA is used as primary prevention in asymptomatic men [1,7]. Some reports have described a small increase in the incidence of stroke in healthy men treated with ASA [8].…”