Abstract Number: PB1253
Meeting: ISTH 2022 Congress
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.
To cite this abstract in AMA style:Alfatani E. What defines Platelet Responsiveness? “Aggregation and secretion are independently regulated” [abstract]. https://abstracts.isth.org/abstract/what-defines-platelet-responsivenessaggregation-and-secretion-are-independently-regulated/. Accessed October 2, 2023.
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