Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood

Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of...

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Autores: Escolar Albaladejo, Ginés, Fernández Gallego, Victor, Arellano Rodrigo, Eduardo, Roquer, Jaume, Reverter Calatayud, Juan Carlos, Sanz, Victoria Veronica, Molina, Patricia, López Vilchez, Irene, Diaz Ricart, M. Isabel, Galán, Ana M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/123858
Acceso en línea:https://hdl.handle.net/2445/123858
Access Level:acceso abierto
Palabra clave:Hemostàsia
Sang
Coagulació sanguínia
Hemostasis
Blood
Blood coagulation
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spelling Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human bloodEscolar Albaladejo, GinésFernández Gallego, VictorArellano Rodrigo, EduardoRoquer, JaumeReverter Calatayud, Juan CarlosSanz, Victoria VeronicaMolina, PatriciaLópez Vilchez, IreneDiaz Ricart, M. IsabelGalán, Ana M.HemostàsiaSangCoagulació sanguíniaHemostasisBloodBlood coagulationApixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s−1. The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM and perfusion studies. Our results indicate that rFVIIa, PCCs and aPCCs have the potential to restore platelet and fibrin components of the hemostasis previously altered by apixaban.Public Library of Science (PLoS)2018201820132018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion7 p.application/pdfhttps://hdl.handle.net/2445/123858Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0078696PLoS One, 2013, vol. 8, num. 11, p. 1-7https://doi.org/10.1371/journal.pone.0078696cc-by (c) Escolar Albaladejo, Ginés et al., 2013http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1238582026-05-29T05:05:01Z
dc.title.none.fl_str_mv Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
title Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
spellingShingle Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
Escolar Albaladejo, Ginés
Hemostàsia
Sang
Coagulació sanguínia
Hemostasis
Blood
Blood coagulation
title_short Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
title_full Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
title_fullStr Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
title_full_unstemmed Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
title_sort Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
dc.creator.none.fl_str_mv Escolar Albaladejo, Ginés
Fernández Gallego, Victor
Arellano Rodrigo, Eduardo
Roquer, Jaume
Reverter Calatayud, Juan Carlos
Sanz, Victoria Veronica
Molina, Patricia
López Vilchez, Irene
Diaz Ricart, M. Isabel
Galán, Ana M.
author Escolar Albaladejo, Ginés
author_facet Escolar Albaladejo, Ginés
Fernández Gallego, Victor
Arellano Rodrigo, Eduardo
Roquer, Jaume
Reverter Calatayud, Juan Carlos
Sanz, Victoria Veronica
Molina, Patricia
López Vilchez, Irene
Diaz Ricart, M. Isabel
Galán, Ana M.
author_role author
author2 Fernández Gallego, Victor
Arellano Rodrigo, Eduardo
Roquer, Jaume
Reverter Calatayud, Juan Carlos
Sanz, Victoria Veronica
Molina, Patricia
López Vilchez, Irene
Diaz Ricart, M. Isabel
Galán, Ana M.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hemostàsia
Sang
Coagulació sanguínia
Hemostasis
Blood
Blood coagulation
topic Hemostàsia
Sang
Coagulació sanguínia
Hemostasis
Blood
Blood coagulation
description Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s−1. The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM and perfusion studies. Our results indicate that rFVIIa, PCCs and aPCCs have the potential to restore platelet and fibrin components of the hemostasis previously altered by apixaban.
publishDate 2013
dc.date.none.fl_str_mv 2013
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/123858
url https://hdl.handle.net/2445/123858
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0078696
PLoS One, 2013, vol. 8, num. 11, p. 1-7
https://doi.org/10.1371/journal.pone.0078696
dc.rights.none.fl_str_mv cc-by (c) Escolar Albaladejo, Ginés et al., 2013
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Escolar Albaladejo, Ginés et al., 2013
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 7 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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