1. The inhibitory effects of aspirin on platelet function in vitro have been shown to be both time (over 3 h) and concentration (1–10 μmol/l) dependent.

2. To determine if these effects occurred in vivo, four volunteers received intravenous infusions on four occasions, to give constant plasma aspirin concentrations of 0, 1, 2 and 4 μmol/l over 3 h. Infusions were performed at intervals of at least 2 weeks.

3. Before and during the infusions, blood was taken for assay of aspirin concentrations, and measurements of platelet aggregation in response to collagen, adenosine 5′-pyrophosphate and arachidonate. Thromboxane generation after stimulated platelet aggregation and whole-blood coagulation was also measured.

4. At each aspirin concentration, both platelet aggregation and thromboxane generation in response to collagen and arachidonate were inhibited progressively over the 3 h infusion period. Greatest inhibition was seen during the 4 μmol/l infusion, which produced maximal or near-maximal inhibition by the third hour.

5. Thromboxane generated during whole-blood coagulation was similarly inhibited in both a time- and concentration-dependent manner throughout all aspirin infusions.

6. The progressive nature of the inhibition of platelet function with these low aspirin concentrations may be due to either slow aspirin transport across the platelet membrane or delayed interaction with cyclo-oxygenase.

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