Category: signaling
Three reinforcing activation loops. (1) Thromboxane A2 from platelet COX-1: aspirin irreversibly acetylates COX-1 → no TXA2 for the platelet's 7-10 d life span. (2) ADP from dense granules → P2Y12 receptor (Gi-coupled) → CLOPIDOGREL (irreversible, prodrug requiring CYP2C19 activation), PRASUGREL (irreversible, more reliable activation), TICAGRELOR (reversible, direct); cangrelor IV. (3) Thrombin → PAR1 (vorapaxar antagonist). Final common path: αIIbβ3 (GPIIb-IIIa) conformational change → fibrinogen binding → cross-linking + aggregation. Abciximab + eptifibatide + tirofiban block αIIbβ3 (PCI use). Combined antiplatelet: dual = aspirin + P2Y12i (standard post-PCI; CV mortality benefit). Bleeding risk scales with intensity + number of agents.