Which of the following antiplatelet agents irreversibly inhibits platelet aggregation by covalently acetylating cyclooxygenase-1 (COX-1)?

Explanation

## Mechanism of Aspirin **Key Point:** Aspirin irreversibly acetylates serine residues on COX-1, permanently blocking thromboxane A₂ (TXA₂) synthesis in platelets. Since platelets lack a nucleus and cannot synthesize new COX-1, this inhibition lasts the entire lifespan of the platelet (7–10 days). ## Why Irreversible? Aspirin's covalent acetylation is unique among antiplatelet agents: - **Clopidogrel, ticagrelor, prasugrel:** P2Y₁₂ receptor antagonists (reversible) - **Dipyridamole:** phosphodiesterase inhibitor (reversible) - **Aspirin alone:** irreversible COX-1 inhibition ## Clinical Implications **High-Yield:** Aspirin must be stopped 5–7 days preoperatively because platelet function cannot recover until new platelets are formed. Other antiplatelet agents (reversible inhibitors) need only 3–5 days washout. **Clinical Pearl:** The irreversible nature makes aspirin ideal for chronic secondary prevention in coronary artery disease and stroke, as once-daily dosing (75–100 mg) maintains consistent antiplatelet effect. ## Comparison Table | Agent | Mechanism | Reversibility | Duration of Action | | --- | --- | --- | --- | | Aspirin | COX-1 acetylation | Irreversible | 7–10 days (platelet lifespan) | | Clopidogrel | P2Y₁₂ antagonist | Reversible | 3–5 days | | Ticagrelor | P2Y₁₂ antagonist | Reversible | 2–3 days | | Dipyridamole | PDE inhibitor | Reversible | 12–24 hours |