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

Abstract

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.

The Antiplatelet Aggregation Effects of Aspirin Suppositories

“…We present data showing that rectal administration of aspirin (200-mg suppositories) also suppressed platelet aggregation very quickly within 30 min and that the suppression continued for 24 h. Our results are consistent with those for oral aspirin showing that aggregation remained suppressed for 48 h after the start of aspirin administration [7, 8]. This long-lasting suppression by aspirin makes it possible for it to be given on a once-a-day basis.…”

“…Oral administration of aspirin suppresses platelet aggregation very quickly within 15 [7]to 120 min [8]. We present data showing that rectal administration of aspirin (200-mg suppositories) also suppressed platelet aggregation very quickly within 30 min and that the suppression continued for 24 h. Our results are consistent with those for oral aspirin showing that aggregation remained suppressed for 48 h after the start of aspirin administration [7, 8].…”

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

“…In 1990, urinary excretion of both 6-keto-prostaglandin F1␣ and thromboxane B2 were found elevated 2 weeks after aspirin was stopped (Vial et al, 1991). Three years later, Mousa et al (1993) showed that although platelets are inhibited by a single dose of aspirin, 6 days after the dose, fibrinogen binding to activated platelets was increased over baseline as was arachidonic acid-induced platelet aggregation. In 1996, the effect of aspirin discontinuation on fibrin-fibrinogen was shown (Fatah et al, 1996).…”

Spontaneous Early Recanalization after Acute Innominate Artery Thromboembolic Occlusion Secondary to Abrupt Aspirin and Statin Discontinuation: A Case Report

“…However, early spontaneous recanalization of an extracranial arterial occlusion (especially an IA occlusion) has rarely been reported. of aspirin administration, whereas an increased thromboembolic effect appears at eight to ten days after drug cessation due to new platelet formation with increased COX-1 activity and rebound inflammation (9)(10)(11). The studies of Sibon and Orgogozo (12) and Maulaz et al (13), have demonstrated that recent aspirin discontinuation is associated with increased stroke risk, with most strokes occurring between six and 10 days after aspirin cessation.…”