Aspirin irreversibly acetylates COX-1 in platelets. Why do platelets never recover COX function after aspirin, while vascular endothelial cells do?

• A Platelets express only COX-2, which is not inhibited by aspirin; endothelial cells express COX-1
• B Aspirin is rapidly metabolized to inactive salicylate in endothelial cells, sparing them
• C Platelet COX-1 has a different active site preventing aspirin deacetylation
• D Platelets lack nuclei and cannot synthesize new COX protein; endothelial cells are nucleated and regenerate COX within 6–8 hours ✓

Explanation

Platelets are anucleate (enucleated during megakaryocyte development) and lack the nuclear DNA and ribosomes needed to synthesize new COX protein. Once acetylated by aspirin, platelet COX-1 is permanently inactivated for the platelet's lifespan (~8–10 days). Vascular endothelial cells have nuclei and can transcribe new COX-2 (inducible) and COX-1 protein within hours, recovering prostacyclin (PGI2) synthesis. This selective, permanent platelet inhibition is the basis for low-dose aspirin's antiplatelet therapy without sustained endothelial prostacyclin suppression.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.