Clinical evidence indicates aspirin is effective in the control of numerous chronic conditions such as atherosclerosis. The principal cardiovascular benefit from aspirin is due to its ability to reduce the incidence and severity of thrombotic episodes. The anticoagulant effect of aspirin occurs through its ability to inhibit which of the following activities?
(A) cyclooxygenase
(B) fibrin cross-linking by factor XIIIa
© phospholipase A2
(D) thrombin binding to activated platelets
(E) von Willebrand factor
Explanation
(A) The synthesis of the cyclic eicosanoids (the prostaglandins and the thromboxanes) begins with the cyclization of arachadonic acid. This reaction is carried out by the enzyme prostaglandin endoperoxide synthetase. This enzyme has two distinct activities, cyclooxygenase and a peroxidase. The activity of the cyclooxygenase domain is inhibited by a class of compounds referred to as the NSAIDs. Aspirin is of this class of drug and, therefore, inhibits the cyclooxygenase activity. The inhibition of prostaglandin synthesis has a negative effect on the process of coagulation through a reduction in the production of TXA2, a potent activator of platelet function. Aspirin also reduces the production of prostacyclin (PGI2) by endothelial cells. PGI2 is a vasodilator and an inhibitor of platelet aggregation. Since endothelial cells regenerate active cyclooxygenase faster than platelets, the net effect of aspirin is more in favor of endothelial cellmediated inhibition of the coagulation cascade. The action of the steroidal anti-inflammatory drugs occurs through the inhibition of phospholipase A2 (choice C), and inhibition of this enzyme has no direct effect on the coagulation process. The other choices (B, D, and E) are not targets for the action of aspirin.