PLATELET RESPONSES TO SEVERAL AGONISTS AND COMBINATIONS OF AGONISTS IN WHOLE BLOOD: A PLACEBO CONTROLLED COMPARISON OF THE EFFECTS OF A ONCE DAILY DOSE OF PLAIN ASPIRIN 300mg, PLAIN ASPIRIN 75mg AND ENTERIC COATED ASPIRIN 300mg, IN MAN.

Abstract

Platelet responses to several agonists and combinations of agonists have been measured in whole blood from healthy volunteers. We have determined the effects of once daily treatment for five days with plain aspirin 300mg, plain aspirin 75mg, enteric coated aspirin 300mg or placebo. Measurements were made of platelet aggregation (using a platelet counting technique) and the release reaction ( 14C-5HT release from pre-labelled platelets). The extents of these responses before aspirin administration depended on the agonist used. ADP, adrenaline and PAF failed to induce any 14C-5HT release in most subjects, but combinations of these agonists acted synergistically to produce extensive 14C-5HT release. All three aspirin preparations reduced the extent of the platelet responses to most agonists: platelet aggregation induced by collagen, ristocetin and arachidonate and 14C-5HT release induced by collagen, streptokinase, and various combinations of ADP, adrenaline and PAF. None of the preparations had any effect on the aggregation that occurred in the absence of an agonist (spontaneous aggregation), but they all reduced streptokinase-induced aggregation to control (spontaneous) levels, and abolished the 14C-5HT release induced by arachidonate and by ristocetin. All three aspirin preparations were equally effective after two daily doses. No further inhibition of platelet responses was obtained after five daily doses. Plain aspirin 300 mg achieved its maximal effect after only a single dose, but enteric coated aspirin 300mg (and sometimes plain aspirin 75mg) produced sub-maximal inhibition after only a single dose. Parallel investigations on the effects of these aspirin regimes on gastric mucosal prostaglandin E 2 synthesis and gastroduodenal mucosal injury were performed. These results will be reported separately. © 1997 Elsevier Science Ltd