Effect of aspirin infusions on platelet function in humans

Area of Science:

• Pharmacology
• Biochemistry
• Hematology

Background:

• In vitro studies demonstrate aspirin's concentration- and time-dependent inhibition of platelet function.
• The in vivo relevance of these findings at low aspirin concentrations requires investigation.

Purpose of the Study:

• To investigate the in vivo effects of low, constant plasma aspirin concentrations on platelet function and thromboxane generation.
• To determine the time and concentration dependency of aspirin's inhibitory effects in humans.

Main Methods:

• Four volunteers received intravenous aspirin infusions at plasma concentrations of 0, 1, 2, and 4 mumol/l over 3 hours.
• Blood samples were analyzed for aspirin levels, platelet aggregation (collagen, adenosine 5'-pyrophosphate, arachidonate), thromboxane generation, and whole-blood coagulation.
• Infusions were separated by at least 2 weeks.

Main Results:

• Platelet aggregation and thromboxane generation in response to collagen and arachidonate were progressively inhibited over 3 hours at all tested aspirin concentrations.
• The 4 mumol/l infusion showed maximal or near-maximal inhibition by the third hour.
• Thromboxane generation during whole-blood coagulation also demonstrated time- and concentration-dependent inhibition.

Conclusions:

• Low-dose aspirin exhibits progressive, time- and concentration-dependent inhibition of platelet function and thromboxane generation in vivo.
• The observed progressive inhibition may be attributed to slow aspirin transport into platelets or delayed interaction with cyclo-oxygenase.
• These findings highlight the in vivo efficacy of low aspirin concentrations in modulating platelet activity.