Int J Med Sci 2019; 16(2):264-275. doi:10.7150/ijms.28580

Research Paper

Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y12 Receptor Antagonists

Bernadeta Chyrchel1, Anna Drożdż2, Dorota Długosz3, Ewa Ł. Stępień4*, Andrzej Surdacki1*✉

1. Second Department of Cardiology, Jagiellonian University Medical College, Cracow, Poland
2. Małopolska Center of Biotechnology, Jagiellonian University, Cracow, Poland
3. Students' Scientific Group at the Second Department of Cardiology, Jagiellonian University Medical College, Cracow, Poland
4. Department of Medical Physics, Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Cracow, Poland
* joint senior authors on this work.

Abstract

Background: Platelet-derived microvesicles (PMVs), shed from platelet surface membranes, constitute the majority of circulating microvesicles and have been implicated in procoagulant, pro-inflammatory and pro-atherosclerotic effects. Our aim was to compare plasma PMVs numbers in relation to platelet reactivity during dual antiplatelet therapy (DAPT) with various P2Y12 adenosine diphosphate (ADP) receptor antagonists.

Methods: In pre-discharge men treated with DAPT for an acute coronary syndrome, plasma PMVs were quantified by flow cytometry on the basis of CD62P (P-selectin) and CD42 (glycoprotein Ib) positivity, putative indices of PMVs release from activated and all platelets, respectively. ADP-induced platelet aggregation was measured by multiple-electrode aggregometry.

Results: Clinical characteristics were similar in patients on clopidogrel (n=16), prasugrel (n=10) and ticagrelor (n=12). Platelet reactivity was comparably reduced on ticagrelor or prasugrel versus clopidogrel (p<0.01). Compared to clopidogrel-treated patients, CD42+/CD62P+ PMVs counts were 3-4-fold lower in subjects receiving ticagrelor (p=0.001) or prasugrel (p<0.05), while CD42+ PMVs were significantly reduced on ticagrelor (by about 6-fold, p<0.001), but not prasugrel (p=0.3). CD42+/CD62P+ PMVs numbers correlated positively to the ADP-induced aggregation on clopidogrel (p<0.01) or prasugrel (p<0.05), which was absent in ticagrelor users (p=0.8). CD42+ PMVs counts were unrelated to platelet reactivity (p>0.5).

Conclusions: Higher antiplatelet potency of prasugrel and ticagrelor versus clopidogrel is associated with decreased plasma CD42+/CD62P+ PMVs numbers. However, in contrast to thienopyridines, the association of reduced CD42+/CD62P+ PMVs counts with ticagrelor use appears independent of its anti-aggregatory effect. Despite similar platelet-inhibitory activity of ticagrelor and prasugrel, only the treatment with ticagrelor seems associated with lower total PMVs release. Our preliminary findings may suggest a novel pleiotropic effect of ticagrelor extending beyond pure anti-aggregatory properties of the drug.

Keywords: dual antiplatelet therapy, P2Y12 antagonists, platelets, microvesicles, ticagrelor

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How to cite this article:
Chyrchel B, Drożdż A, Długosz D, Stępień EŁ, Surdacki A. Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y12 Receptor Antagonists. Int J Med Sci 2019; 16(2):264-275. doi:10.7150/ijms.28580. Available from http://www.medsci.org/v16p0264.htm