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Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists

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...

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Autores principales: Chyrchel, Bernadeta, Drożdż, Anna, Długosz, Dorota, Stępień, Ewa Ł., Surdacki, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367525/
https://www.ncbi.nlm.nih.gov/pubmed/30745807
http://dx.doi.org/10.7150/ijms.28580
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author Chyrchel, Bernadeta
Drożdż, Anna
Długosz, Dorota
Stępień, Ewa Ł.
Surdacki, Andrzej
author_facet Chyrchel, Bernadeta
Drożdż, Anna
Długosz, Dorota
Stępień, Ewa Ł.
Surdacki, Andrzej
author_sort Chyrchel, Bernadeta
collection PubMed
description 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 P2Y(12) 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.
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spelling pubmed-63675252019-02-11 Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists Chyrchel, Bernadeta Drożdż, Anna Długosz, Dorota Stępień, Ewa Ł. Surdacki, Andrzej Int J Med Sci Research Paper 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 P2Y(12) 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. Ivyspring International Publisher 2019-01-01 /pmc/articles/PMC6367525/ /pubmed/30745807 http://dx.doi.org/10.7150/ijms.28580 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Chyrchel, Bernadeta
Drożdż, Anna
Długosz, Dorota
Stępień, Ewa Ł.
Surdacki, Andrzej
Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists
title Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists
title_full Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists
title_fullStr Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists
title_full_unstemmed Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists
title_short Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y(12) Receptor Antagonists
title_sort platelet reactivity and circulating platelet-derived microvesicles are differently affected by p2y(12) receptor antagonists
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367525/
https://www.ncbi.nlm.nih.gov/pubmed/30745807
http://dx.doi.org/10.7150/ijms.28580
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