EFFECTS OF LOW-DOSE ASPIRIN ON IN-VITRO PLATELET-AGGREGATION IN THE EARLY MINUTES AFTER INGESTION IN NORMAL SUBJECTS

Aspirin interferes with platelet aggregation by inhibiting the metabolism of arachidonic acid to thromboxane A(2). Although both high- and low-dose aspirin therapies are effective for secondary prophylaxis in patients with atherosclerotic vascular disease, the acute response to low-dose aspirin therapy is controversial. Eighteen volunteer subjects ingested 81, 162, or 324 mg of aspirin in a longitudinal crossover study design. Initial doses were randomly assigned and dosing intervals were separated by 2 weeks. Platelet aggregation in response to 0.9 mM arachidonic acid was measured at baseline, 15, 30, 60, and 90 minutes after ingestion. Thromboxane B-2 production was assayed on simultaneously obtained samples after stimulation with arachidonic acid. The median inhibition of aggregation was 97%, 97%, and 97% 15 minutes after ingestion of 81, 162, and 324 mg, respectively. Four subjects had <20% inhibition 15 minutes after ingesting 81 mg, but all 4 had >90% inhibition after 30 minutes. Thromboxane B-2 production declined by >93% in all subjects at each dose. There was no difference between doses in inhibition of thromboxane B-2 production.