TITLE:
Evaluation of the Effect of Aspirin on Platelet Aggregation: Methodological Recommendations for Aspirin-Drug Interaction Studies
AUTHORS:
Annelieke C. Kruithof, Matthijs Moerland, Eleftheria A. Anastasopoulou, Pieter-Jan de Kam, Marieke L. de Kam, Jacobus Burggraaf
KEYWORDS:
Platelet Aggregation, Impedance Aggregometry, Whole Blood, Collagen, Aspirin Interaction
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.8 No.1,
January
19,
2015
ABSTRACT: Given the broad application of aspirin as antiplatelet drug, availability of standardized methodology to assess potential interaction with any co-medication on platelet aggregation is desired. We characterized the effect of aspirin (ASA) therapy on collagen-induced platelet aggregation in whole blood to define such methodology. Collagen-induced platelet whole blood aggregation was assessed in 6 healthy male volunteers on 2 occasions (Day 1, Day 7) using the Chronolog aggregometer. From Day 2 up to Day 7, subjects received a daily oral dose of 75 mg ASA. The relationship between collagen dose and platelet aggregation response was assessed. On Day 1, maximal aggregation was observed at 1 μg/mL collagen (15.3 ± 4.6 Ω) and higher. Reproducible results were obtained without any indication of intra-subject fluctuations. ASA treatment decreased maximal aggregation by 80% and 38% at 0.5 and 2.0 μg/mL collagen, respectively. Power calculations were performed based on the observed intra-subject variability and demonstrated minimal sample sizes of 9 - 11 subjects for future cross-over ASA-drug interaction studies exploring effects on platelet aggregation, which demonstrates that the proposed collagen-induced ex vivo whole blood platelet aggregation is a feasible methodology to evaluate ASA-drug interactions in healthy volunteers.