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      Effect of Single Oral Dose of Aspirin on Human Platelet Functions and Plasma Plasminogen Activator Inhibitor-1

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          Previous reports documented the inhibitory efficacy of different doses of aspirin on arachidonic acid (AA)-induced platelet aggregation, however, the sensitivity of platelets toward other agonists as well as the effects of aspirin on platelet and plasma plasminogen activator inhibitor-1 (PAI-1) release and levels were not investigated. Hence, the present study was undertaken to investigate the effect and duration of action of a single oral dose (650 mg) of aspirin on human platelet functions (n = 34, normal healthy male and female volunteers) including aggregation, fibrinogen binding and PAI-1 release, and on the plasma level of PAI-1. Aspirin demonstrated a rapid onset of action (at 2 h after ingestion) in specifically inhibiting ex vivo AA-mediated functions including (a) fibrinogen binding to gel-purified platelets, (b) platelet aggregation, and (c) platelet PAI-1 release. A peak reduction of plasma PAI-1 level at 2 h was demonstrated as well. The effect of aspirin on the ex vivo AA-mediated effects (a-c) was shown to last for up to 4 days. However, aspirin treatment resulted in a rebound effect in platelet function (a-c) to other platelet agonists such as adenosine diphosphate or the combination of agonists including adenosine diphosphate, 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 response to other agonists suggests the potential usefulness of a combination therapy of aspirin with other antiplatelet drugs, as well as the potential advantages for other platelet inhibitors such as GpIIb/IIIa receptor antagonists.

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          Author and article information

          S. Karger AG
          18 November 2008
          : 83
          : 5-6
          : 367-373
          DuPont Merck Pharmaceutical Company, Cardiovascular Diseases Division, Exp. Station, Wilmington, Del., USA
          175993 Cardiology 1993;83:367–373
          © 1993 S. Karger AG, Basel

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          Page count
          Pages: 7
          Clinical Pharmacology


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