NSAIDs antiplatelet action

Most NSAIDs are nonselective inhibitors of cyclooxygenases, acting on both COX 1 and COX 2 isoforms to decrease formation of PGs and thromboxanes. This action is a primary (but not sole) contributor to the pharmacologic actions of NSAIDs. These actions include analgesic, antipyretic, anti-inflammatory, and antiplatelet effects. Acetylsalicylic acid (ASA) is the prototype of the group, which includes more than 20 individual drugs. 

The antiplatelet action of aspirin results from the fact that inhibition of thromboxane synthesis is essentially permanent in platelets they lack the machinery for new protein synthesis. In contrast, inhibition of prostacyclin synthesis in the vascular endothelium is temporary because these cells can synthesize new enzyme. Inhibition of prostaglandin synthesis also results in important anti-inflammatory effects. Inhibition of synthesis of fever-inducing prostaglandins in the brain produces the antipyretic action of NSAIDs. Closure of a patent ductus arteriosus in an otherwise normal infant can be accelerated with a potent NSAID such as indomethacin. 

B. Mechanism of Action Aspirin and other NSAIDs inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase. Thromboxane is a potent stimulator of platelet aggregation. Aspirin is particularly effective because it irreversibly inactivates the enzyme. Because the platelet lacks the machinery for synthesis of new protein, inhibition by aspirin persists until new platelets are formed (several days). Other NSAIDs cause a less persistent antiplatelet effect (hours). 

Fondaparinux commonly causes bleeding as a consequence of its action. Since antiplatelet drugs and NSAIDs also increase the risk of bleeding, the risk and severity of bleeding is likely to be increased with the combination. 

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