EFFECT OF SINGLE ORAL DOSE OF ASPIRIN ON HUMAN PLATELET FUNCTIONS ANDPLASMA PLASMINOGEN-ACTIVATOR INHIBITOR-1

Previous reports documented the inhibitory efficacy of different doses of aspirin on arachidonic acid (AA)-induced platelet aggregation, how ever, the sensitivity of platelets toward other agonists as well as th e effects of aspirin on platelet and plasma plasminogen activator inhi bitor-1 (PAI-1) release and levels were not investigated. Hence, the p resent study was undertaken to investigate the effect and duration of action of a single oral dose (650 mg) of aspirin on human platelet fun ctions (n = 34, normal healthy male and female volunteers) including a ggregation, fibrinogen binding and PAI-1 release, and on the plasma le vel of PAI-1. Aspirin demonstrated a rapid onset of action (at 2 h aft er ingestion) in specifically inhibiting ex vivo AA-mediated functions including (a) fibrinogen binding to gel-purified platelets, (b) plate let aggregation, and (c) platelet PAI-1 release. A peak reduction of p lasma PAI-1 level at 2 h was demonstrated as well. The effect of aspir in on the ex vivo AA-mediated effects (a-c) was shown to last for up t o 4 days. However, aspirin treatment resulted in a rebound effect in p latelet function (a-c) to other platelet agonists such as adenosine di phosphate or the combination of agonists including adenosine diphospha te, epinephrine, and AA, In conclusion, a single oral dose of aspirin has long-lasting effects on AA-induced platelet activation and reduces plasma levels of PAI- 1 as well. The rebound effect of platelets in r esponse to other agonists suggests the potential usefulness of a combi nation therapy of aspirin with other antiplatelet drugs, as well as th e potential advantages for other platelet inhibitors such as GpIIb/III a receptor antagonists.