PhD Student School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland,123 St Stephens Green, Dublin 2; ebtihalalfatani@rcsi.com Sandyford, Dublin, Ireland
Background: Platelet activation plays an important role in arterial thrombosis in coronary heart disease, stroke, and peripheral arterial disease.
Aims: Therefore this study aims to determine if platelet aggregation is a true measure of global platelet responsiveness; or whether ATP secretion may reveal a different dynamic. .
Methods: 108 normal healthy volunteers were assessed for indices of platelet function, in response to 3 different agonists over a physiological dose range as follows: thrombin receptor activating peptide (TRAP; 2.9-33uM), collagen-related peptide (CRP-XL; 0.1-2 ug/ml) and thromboxane A2-mimetic (U46619; 0.1-15 uM). Specifically, we examined the dose-response nature of each individual’s responsiveness to platelet agonists in parallel assays of platelet aggregation (assessed by light transmission in PRP) and platelet ATP secretion (assessed by luminometry).
Results: The results show significant inter-individual differences in aggregation and secretion responses to all 3 agonists in the donor population. For example, the maximal extent of platelet aggregation varies in response to TRAP from a minimum 31.50% to maximum 120%). Similarly, the maximal extent of ATP secreted in response to TRAP from minimum 0.11 to maximum 4.67 pmoles / 106 platelets, demonstrating a 40 to 50 fold range in secretion-capacity for this dense-granule component. A greater than 10 fold difference in secretion of ATP was also observed in response to CRP and U46619 in this donor cohort. There is a strong positive correlation between responses to all 3 agonists in the aggregation assays and, separately, in the secretion assays. However, there is no correlation between platelet secretion and aggregation responses.
Conclusion(s): Substantial inter-individual variations in platelet responses are observed in normal healthy donors using 3 different agonists (TRAP; CRP and U46619). Aggregation and secretion are independently regulated, suggesting that more studies are merited to investigate if ATP secretion might provide better insights into clinical risks in patient populations.
