THE EFFECTS OF VARYING DOSES OF ASPIRIN ON HUMAN PLATELET ACTIVATION INDUCED BY PAF, COLLAGEN AND ARACHIDONIC-ACID

1 The effect of increasing doses of orally administered aspirin (30-900 mg) on platelet aggregation and ATP release induced by arachidonic acid (AA), collagen and platelet activating factor (PAF) was assessed in 12 normal volunteers. 2 Aspirin ingestion was associated with a significant increase in EC50 for AA (P < 0.0001) and collagen (P < 0.0001) but not for PAF (P > 0.495) although the normal biphasic aggregation response for the latter was abolished. Maximum ATP release was reduced by aspirin for all three agonists. 3 The mean maximum degrees of inhibition of platelet aggregation induced by aspirin for AA, collagen and PAF were 100%, 48% and 21% of baseline, respectively. The corresponding mean maximum inhibition of ATP release was 100%, 63% and 57%. The minimum cumulative doses of aspirin producing these effects were 240, 240 and 90 mg for AA, collagen and PAF respectively. For collagen alone, there was a significant decrease in the degree of inhibition of aggregation between the last dose on day 1 (150 mg) and the baseline measurement on day 2. 4 Platelets from female subjects were more sensitive to collagen (P < 0. 05) and AA (P < 0.01) stimulation compared with males. However, prior to aspirin ingestion, PAF produced a greater maximum response in platelets from females (P < 0.02) while following aspirin ingestion PAF-induced activation was inhibited to a greater degree in females (P < 0.02). 5 These results indicate that collagen- and PAF-induced platelet activation are only partially dependent on cyclo-oxygenase and for PAF this seems related only to the second phase of aggregation. The data also indicates that for platelet aggregation, the agonist and the sex of the subjects influence the degree of inhibition obtained with aspirin and these factors may be important when determining the optimum dose of aspirin for clinical use.