Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens

Martínez-Sánchez, Julia; Castrillo, Leticia; Jerez, Didac; Torramade-Moix, Sergi; Palomo, Marta; Mendieta, Guiomar; Zafar, M. Urooj; Moreno-Castaño, Ana Belen; Sánchez Fernández, Pablo; Badimón, Juan José; Díaz-Ricart, Maribel; Escolar, Ginés; Roque, Mercè; Bristol Myers Squibb Foundation

Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens

12 pages, 7 figures, 1 table, supplementary information https://doi.org/10.1038/s41598-023-50347-2.--Data availability: All authors agree that all data and materials support the published claims and comply with field standards

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Main Authors:	Martínez-Sánchez, Julia, Castrillo, Leticia, Jerez, Didac, Torramade-Moix, Sergi, Palomo, Marta, Mendieta, Guiomar, Zafar, M. Urooj, Moreno-Castaño, Ana Belen, Sánchez Fernández, Pablo, Badimón, Juan José, Díaz-Ricart, Maribel, Escolar, Ginés, Roque, Mercè
Other Authors:	Bristol Myers Squibb Foundation
Format:	artículo biblioteca
Language:	English
Published:	Nature Publishing Group 2023-12
Subjects:	Ensure healthy lives and promote well-being for all at all ages,
Online Access:	http://hdl.handle.net/10261/348039
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spelling	dig-icm-es-10261-3480392024-02-22T12:59:19Z Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens Martínez-Sánchez, Julia Castrillo, Leticia Jerez, Didac Torramade-Moix, Sergi Palomo, Marta Mendieta, Guiomar Zafar, M. Urooj Moreno-Castaño, Ana Belen Sánchez Fernández, Pablo Badimón, Juan José Díaz-Ricart, Maribel Escolar, Ginés Roque, Mercè Bristol Myers Squibb Foundation Pfizer Instituto de Salud Carlos III Fundació La Marató de TV3 Friends of José Carreras International Leukemia Foundation Generalitat de Catalunya Agencia Estatal de Investigación (España) Ensure healthy lives and promote well-being for all at all ages 12 pages, 7 figures, 1 table, supplementary information https://doi.org/10.1038/s41598-023-50347-2.--Data availability: All authors agree that all data and materials support the published claims and comply with field standards We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration This study was supported by an ERISTA grant sponsored by Bristol Myers Squibb (BMS) and Pfizer. The study was partially supported by Instituto de Salud Carlos III (FIS PI19/00888), Fundació Marató de TV3 (202026-10), Deutsche José Carreras Leukämie-Stiftung (03R/ 2019), Generalitat de Catalunya (2017-SGR675, CERCA) With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S) Peer reviewed 2024-02-22T12:57:58Z 2024-02-22T12:57:58Z 2023-12 artículo Scientific Reports 13: 22969 (2023) CEX2019-000928-S http://hdl.handle.net/10261/348039 10.1038/s41598-023-50347-2 2045-2322 en Publisher's version https://doi.org/10.1038/s41598-023-50347-2 Sí open Nature Publishing Group
institution	ICM ES
collection	DSpace
country	España
countrycode	ES
component	Bibliográfico
access	En linea
databasecode	dig-icm-es
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region	Europa del Sur
libraryname	Biblioteca del ICM España
language	English
topic	Ensure healthy lives and promote well-being for all at all ages Ensure healthy lives and promote well-being for all at all ages
spellingShingle	Ensure healthy lives and promote well-being for all at all ages Ensure healthy lives and promote well-being for all at all ages Martínez-Sánchez, Julia Castrillo, Leticia Jerez, Didac Torramade-Moix, Sergi Palomo, Marta Mendieta, Guiomar Zafar, M. Urooj Moreno-Castaño, Ana Belen Sánchez Fernández, Pablo Badimón, Juan José Díaz-Ricart, Maribel Escolar, Ginés Roque, Mercè Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
description	12 pages, 7 figures, 1 table, supplementary information https://doi.org/10.1038/s41598-023-50347-2.--Data availability: All authors agree that all data and materials support the published claims and comply with field standards
author2	Bristol Myers Squibb Foundation
author_facet	Bristol Myers Squibb Foundation Martínez-Sánchez, Julia Castrillo, Leticia Jerez, Didac Torramade-Moix, Sergi Palomo, Marta Mendieta, Guiomar Zafar, M. Urooj Moreno-Castaño, Ana Belen Sánchez Fernández, Pablo Badimón, Juan José Díaz-Ricart, Maribel Escolar, Ginés Roque, Mercè
format	artículo
topic_facet	Ensure healthy lives and promote well-being for all at all ages
author	Martínez-Sánchez, Julia Castrillo, Leticia Jerez, Didac Torramade-Moix, Sergi Palomo, Marta Mendieta, Guiomar Zafar, M. Urooj Moreno-Castaño, Ana Belen Sánchez Fernández, Pablo Badimón, Juan José Díaz-Ricart, Maribel Escolar, Ginés Roque, Mercè
author_sort	Martínez-Sánchez, Julia
title	Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
title_short	Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
title_full	Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
title_fullStr	Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
title_full_unstemmed	Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
title_sort	antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
publisher	Nature Publishing Group
publishDate	2023-12
url	http://hdl.handle.net/10261/348039
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Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens

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