Increased Platelet Sensitivity to Collagen in Individuals Resistant to Low-Dose Aspirin

Abstract

Background and Purpose —The purpose of this study was to assess individual differences in the pharmacological effects of acetylsalicylic acid (ASA) on bleeding time as measured by in vitro platelet aggregation and to examine the consistency of responses over time. Methods —We measured template IIR bleeding time and platelet aggregation in 8 healthy male volunteers before and 2 hours after ingestion of 324 mg of ASA. An individual was considered a nonresponder if his post-ASA bleeding time was not 2 SDs above his baseline bleeding time, where SD was estimated from the baseline bleeding times of the 8 volunteers. The same experiment was done after a 30-month interval. Results —Five volunteers were identified as ASA responders, and 3 were identified as nonresponders. Bleeding time before and after ingestion of ASA was 408±121 seconds (mean±SD) and 720±225 seconds, respectively, in ASA responders and 330±30 seconds and 330±52 seconds, respectively, in ASA nonresponders. The mean ED 50 for collagen-induced platelet aggregation, that is, the mean concentration of collagen that caused a response at 50% of maximum, was 0.91 μg/mL (95% CI, 0.73 to 1.14) in ASA responders and 0.48 μg/mL (95% CI, 0.38 to 0.60) in nonresponders. When optimum concentrations of collagen, ie, concentrations that yielded 90% maximum aggregation, were used as stimuli, the mean IC 50 for ASA, that is, the mean concentration that yielded 50% inhibition, was 322.5 μmol/L (95% CI, 264.8 to 392.6) in ASA responders and 336.1 μmol/L (95% CI, 261.0 to 432.8) in nonresponders. The variability in individual responsiveness in the second experiment remained consistent with that in the first experiment. Conclusions —ASA resistance may be caused by an increased sensitivity of platelets to collagen. A platelet aggregation study specific for collagen dose response may be useful for strict selection of ASA responders for low-dose ASA therapy and for identifying ASA nonresponders for high-dose ASA therapy.