Celecoxib inhibits COX-2 selectively. Which mechanism explains the increased cardiovascular thrombotic risk associated with selective COX-2 inhibitors?

• A Reduction in prostacyclin (PGI2) production in endothelium without reducing platelet thromboxane A2, tilting the balance toward thrombosis ✓
• B Inhibition of thromboxane A2 production in platelets reduces platelet aggregation, causing paradoxical thrombosis
• C Direct activation of coagulation cascade by the drug itself
• D Increased AT-III consumption mediated by COX-2 inhibition in hepatocytes

Explanation

Prostacyclin (PGI2) is produced by vascular endothelium via COX-2 and is antithrombotic and vasodilatory. Thromboxane A2 (TXA2) is produced by platelets via COX-1 and is prothrombotic. Selective COX-2 inhibitors reduce endothelial PGI2 without affecting platelet TXA2, tipping the thromboxane-prostacyclin balance toward thrombosis and vasoconstriction. Non-selective NSAIDs inhibit both, partially preserving this balance. This mechanism explains the cardiovascular harm seen with rofecoxib and class effects of COX-2 inhibitors.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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