Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100 (R)

Background. Anti-platelet drug therapy is currently performed without monit oring. because the established method of platelet aggregometry is cumbersom e. The recently developed platelet function analyzer PFA-100(R) measures sh eer stress dependent, collagen epinephrine (CEPI) and collagen adenosine di phosphate (CADP) induced platelet plug formation. As the PFA-100 provides a valuable tool to detect patients with platelet dysfunction more efficientl y and cost-effectively than aggregometry, we investigated its potential to monitor the efficacy of aspirin treatment. Methods. All healthy volunteers (n = 10) received a fractionated infusion o f L-aspirin to establish individual dose-response curves. Further, in a ran domized, double-blind, placebo controlled two-way cross over study the same volunteers received either 50 or 100 mg aspirin/day p.o. for a period of 1 1 days to determine the day-to-day variability CEPI induced closure time (C T) under constant intake of low dose aspirin. and to compare the efficacy o f those two doses. Results. Intra- and intersubject variability of CEPI-CT averaged 9% and 22% . respectively. Seven volunteers exceeded the maximum of CEPI-CT (>300 s) a lready after infusion of 100 mg L-aspirin. Intake of 100 mg of aspirin elic ited a more rapid onset of effect than 50 me. which was only significant on days 3 and 4 of aspirin intake. The aspirin induced CEPI-CT prolongation c orrelated positively with basal CEPI-CT values (r = 0.86, p = 0.001) and we re strongly dependent on von Willebrand Factor levels (r = -0.9; p = 0.001) . Conclusion. Thus. the PFA-100 system appears suitable to demonstrate an asp irin-induced platelet effect in a longitudinal study, and may be adequate t o monitor a patients compliance. However, prospective trials have to be con ducted to demonstrate whether the EPI-CT achieved under ASA-intake has pred ictive value for cardiovascular outcome.