Aspirin irreversibly inhibits COX, but its antiplatelet effect (at low doses) outlasts its plasma half-life of ~20 minutes. The reason the antiplatelet effect persists for 7-10 days is:
- A Aspirin's active metabolite salicylate continues to inhibit platelet COX throughout platelet lifespan
- B Platelets are anucleate and cannot synthesize new COX-1 protein; TXA2 production is eliminated for the platelet's lifespan ✓
- C Aspirin covalently modifies arachidonic acid in the platelet membrane preventing COX substrate access
- D Portal first-pass effect creates persistent high salicylate concentrations in splanchnic vessels
Correct answer: B. Platelets are anucleate and cannot synthesize new COX-1 protein; TXA2 production is eliminated for the platelet's lifespan
Explanation
Aspirin acetylates a serine residue (Ser529) in COX-1 irreversibly, permanently inactivating thromboxane A2 synthesis in the platelet. Because mature platelets lack a nucleus and the protein synthesis machinery needed to produce new COX-1, the inhibitory effect persists for the entire 7-10 day lifespan of each affected platelet. New unaffected platelets entering the circulation gradually restore thromboxane synthesis, which is why antiplatelet effect reverses 3-5 days after stopping aspirin in most patients.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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