Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.

Increased residual platelet reactivity remains a burden for coronary artery disease (CAD) patients who received a coronary stent and do not respond sufficiently to treatment with acetylsalicylic acid and clopidogrel. We hypothesized that serotonin antagonism reduces high on-treatment platelet reacti...

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Autores principales:	Daniel Duerschmied, Ingo Ahrens, Maximilian Mauler, Christoph Brandt, Stefanie Weidner, Christoph Bode, Martin Moser
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/59bf5da1feeb4e0da8ab90193bfb2df1
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spelling	oai:doaj.org-article:59bf5da1feeb4e0da8ab90193bfb2df12021-11-18T07:26:36ZSerotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.1932-620310.1371/journal.pone.0032656https://doaj.org/article/59bf5da1feeb4e0da8ab90193bfb2df12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22384279/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Increased residual platelet reactivity remains a burden for coronary artery disease (CAD) patients who received a coronary stent and do not respond sufficiently to treatment with acetylsalicylic acid and clopidogrel. We hypothesized that serotonin antagonism reduces high on-treatment platelet reactivity. Whole blood impedance aggregometry was performed with arachidonic acid (AA, 0.5 mM) and adenosine diphosphate (ADP, 6.5 µM) in addition to different concentrations of serotonin (1-100 µM) in whole blood from 42 CAD patients after coronary stent placement and 10 healthy subjects. Serotonin increased aggregation dose-dependently in CAD patients who responded to clopidogrel treatment: After activation with ADP, aggregation increased from 33.7 ± 1.3% to 40.9 ± 2.0% in the presence of 50 µM serotonin (p<0.05) and to 48.2 ± 2.0% with 100 µM serotonin (p<0.001). The platelet serotonin receptor antagonist ketanserin decreased ADP-induced aggregation significantly in clopidogrel low-responders (from 59.9 ± 3.1% to 37.4 ± 3.5, p<0.01), but not in clopidogrel responders. These results were confirmed with light transmission aggregometry in platelet-rich plasma in a subset of patients. Serotonin hence increased residual platelet reactivity in patients who respond to clopidogrel after coronary stent placement. In clopidogrel low-responders, serotonin receptor antagonism improved platelet inhibition, almost reaching responder levels. This may justify further investigation of triple antiplatelet therapy with anti-serotonergic agents.Daniel DuerschmiedIngo AhrensMaximilian MaulerChristoph BrandtStefanie WeidnerChristoph BodeMartin MoserPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e32656 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Duerschmied Ingo Ahrens Maximilian Mauler Christoph Brandt Stefanie Weidner Christoph Bode Martin Moser Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
description	Increased residual platelet reactivity remains a burden for coronary artery disease (CAD) patients who received a coronary stent and do not respond sufficiently to treatment with acetylsalicylic acid and clopidogrel. We hypothesized that serotonin antagonism reduces high on-treatment platelet reactivity. Whole blood impedance aggregometry was performed with arachidonic acid (AA, 0.5 mM) and adenosine diphosphate (ADP, 6.5 µM) in addition to different concentrations of serotonin (1-100 µM) in whole blood from 42 CAD patients after coronary stent placement and 10 healthy subjects. Serotonin increased aggregation dose-dependently in CAD patients who responded to clopidogrel treatment: After activation with ADP, aggregation increased from 33.7 ± 1.3% to 40.9 ± 2.0% in the presence of 50 µM serotonin (p<0.05) and to 48.2 ± 2.0% with 100 µM serotonin (p<0.001). The platelet serotonin receptor antagonist ketanserin decreased ADP-induced aggregation significantly in clopidogrel low-responders (from 59.9 ± 3.1% to 37.4 ± 3.5, p<0.01), but not in clopidogrel responders. These results were confirmed with light transmission aggregometry in platelet-rich plasma in a subset of patients. Serotonin hence increased residual platelet reactivity in patients who respond to clopidogrel after coronary stent placement. In clopidogrel low-responders, serotonin receptor antagonism improved platelet inhibition, almost reaching responder levels. This may justify further investigation of triple antiplatelet therapy with anti-serotonergic agents.
format	article
author	Daniel Duerschmied Ingo Ahrens Maximilian Mauler Christoph Brandt Stefanie Weidner Christoph Bode Martin Moser
author_facet	Daniel Duerschmied Ingo Ahrens Maximilian Mauler Christoph Brandt Stefanie Weidner Christoph Bode Martin Moser
author_sort	Daniel Duerschmied
title	Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
title_short	Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
title_full	Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
title_fullStr	Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
title_full_unstemmed	Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
title_sort	serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/59bf5da1feeb4e0da8ab90193bfb2df1
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Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.

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