Aspirin inhibits COX-1 and COX-2 irreversibly, while selective COX-2 inhibitors (coxibs) are associated with increased cardiovascular risk. The mechanism underlying increased thrombotic risk with coxibs is:

• A COX-2 selective inhibition increases thromboxane A2 (TXA2) synthesis in platelets, promoting aggregation
• B Inhibition of vascular endothelial COX-2-derived prostacyclin (PGI2) without affecting platelet TXA2 synthesis, tipping the balance toward thrombosis ✓
• C Coxibs directly activate platelet ADP receptors, increasing aggregation
• D Selective COX-2 blockade increases leukotriene synthesis, which causes platelet aggregation

Explanation

Vascular endothelium expresses COX-2, which synthesises prostacyclin (PGI2) — a potent vasodilator and platelet aggregation inhibitor. Platelets express only COX-1, which produces TXA2 (vasoconstrictor and proaggregatory). Coxibs selectively inhibit endothelial COX-2-derived PGI2 while leaving platelet COX-1/TXA2 intact, shifting the TXA2/PGI2 balance toward thrombosis. Aspirin, by inhibiting both COX isoforms irreversibly, still provides a net antithrombotic effect predominantly through platelet COX-1 blockade.

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

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Written and medically reviewed by the StethoPrep medical team.