Aspirin irreversibly inhibits platelet cyclooxygenase. Which pharmacodynamic property explains why its antiplatelet effect lasts 8–10 days even though aspirin's plasma half-life is only 20 minutes?

• A Aspirin's acetyl group is hydrolysed so slowly by plasma esterases that new COX is inhibited throughout the drug's 10-day tissue half-life
• B Anucleate platelets cannot synthesise new COX protein, so inhibition persists for the platelet lifespan ✓
• C Aspirin acetylates megakaryocyte COX in the bone marrow causing sustained inhibition of newly released platelets
• D Salicylate metabolite competitively inhibits COX throughout the platelet lifespan

Explanation

Aspirin covalently acetylates serine-530 of COX-1 (and COX-2) in platelets, irreversibly inactivating the enzyme. Because mature circulating platelets are anucleate (no nucleus), they cannot transcribe or translate new COX protein to replace the inhibited enzyme. The functional antiplatelet effect therefore persists for the entire platelet lifespan (8–10 days), even though plasma aspirin is cleared within minutes. Nucleated cells (vascular endothelium, vascular smooth muscle) can re-synthesise COX within hours — which is why low-dose aspirin spares prostacyclin (PGI2) production more than TXA2 over repeated dosing.

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

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