Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -

BACKGROUND: Despite the good safety of rivaroxaban, there is limited information on strategies for urgent reversal of its antihemostatic effects.Methods and Results:Alterations of hemostasis induced by rivaroxaban (230 ng/ml) were assessed by using several tests applied to steady and circulating hum...

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Autores: Escolar Albaladejo, Ginés, Arellano Rodrigo, Eduardo, López Vilchez, Irene, Molina, Patricia, Sanchis Forés, Juan, Reverter Calatayud, Juan Carlos, Carné Cladellas, Xavier, Cid Vidal, Joan, Villalta i Blanch, Jaume, Tàssies Penella, María Dolores, Galan, Ana M., Diaz Ricart, M. Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/113934
Acceso en línea:https://hdl.handle.net/2445/113934
Access Level:acceso abierto
Palabra clave:Coagulació sanguínia
Hemostàsia
Assaigs clínics de medicaments
Medicaments
Blood coagulation
Hemostasis
Drug testing
Drugs
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spelling Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -Escolar Albaladejo, GinésArellano Rodrigo, EduardoLópez Vilchez, IreneMolina, PatriciaSanchis Forés, JuanReverter Calatayud, Juan CarlosCarné Cladellas, XavierCid Vidal, JoanVillalta i Blanch, JaumeTàssies Penella, María DoloresGalan, Ana M.Diaz Ricart, M. IsabelCoagulació sanguíniaHemostàsiaAssaigs clínics de medicamentsMedicamentsBlood coagulationHemostasisDrug testingDrugsBACKGROUND: Despite the good safety of rivaroxaban, there is limited information on strategies for urgent reversal of its antihemostatic effects.Methods and Results:Alterations of hemostasis induced by rivaroxaban (230 ng/ml) were assessed by using several tests applied to steady and circulating human blood. Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were measured. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with circulating blood. The potential reversal of prothrombin complex concentrates (PCCs; 50 IU/kg), activated PCCs (aPCCs; 75 IU/kg), or recombinant factor VIIa (rFVIIa; 270 μg/kg) was evaluated. Impairment of TG parameters induced by rivaroxaban were corrected by the different concentrates (aPCC≥PCC>rFVIIa). Prolonged clotting times and reduced clot firmness caused by rivaroxaban on TEM tests were improved by different concentrates (rFVIIa≥aPCC>PCC). Rivaroxaban significantly reduced platelets and fibrin interactions with damaged vascular surfaces in perfusion studies. While alterations of platelet interactions were favourably counteracted by rFVIIa or aPCCs, reductions in fibrin formation were only partially restored by the different factor concentrates (rFVIIa>aPCC≥PCC). CONCLUSIONS: Rivaroxaban-induced alterations on coagulation parameters measured through assays performed under static conditions were easily reversed by the different concentrates. Studies under flow conditions revealed that these concentrates normalized the action of rivaroxaban on platelets, and significantly improved fibrin formation; although in the later case, levels were not restored to the pre-treatment value. (Circ J 2015; 79: 331-338).Japanese Circulation Society2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/113934Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1253/circj.CJ-14-0909Circulation Journal, 2015, vol. 79, num. 2, p. 331-338https://doi.org/10.1253/circj.CJ-14-0909(c) Japanese Circulation Society, 2015info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1139342026-05-27T06:46:51Z
dc.title.none.fl_str_mv Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
title Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
spellingShingle Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
Escolar Albaladejo, Ginés
Coagulació sanguínia
Hemostàsia
Assaigs clínics de medicaments
Medicaments
Blood coagulation
Hemostasis
Drug testing
Drugs
title_short Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
title_full Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
title_fullStr Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
title_full_unstemmed Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
title_sort Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates - In vitro studies with steady and circulating human blood -
dc.creator.none.fl_str_mv Escolar Albaladejo, Ginés
Arellano Rodrigo, Eduardo
López Vilchez, Irene
Molina, Patricia
Sanchis Forés, Juan
Reverter Calatayud, Juan Carlos
Carné Cladellas, Xavier
Cid Vidal, Joan
Villalta i Blanch, Jaume
Tàssies Penella, María Dolores
Galan, Ana M.
Diaz Ricart, M. Isabel
author Escolar Albaladejo, Ginés
author_facet Escolar Albaladejo, Ginés
Arellano Rodrigo, Eduardo
López Vilchez, Irene
Molina, Patricia
Sanchis Forés, Juan
Reverter Calatayud, Juan Carlos
Carné Cladellas, Xavier
Cid Vidal, Joan
Villalta i Blanch, Jaume
Tàssies Penella, María Dolores
Galan, Ana M.
Diaz Ricart, M. Isabel
author_role author
author2 Arellano Rodrigo, Eduardo
López Vilchez, Irene
Molina, Patricia
Sanchis Forés, Juan
Reverter Calatayud, Juan Carlos
Carné Cladellas, Xavier
Cid Vidal, Joan
Villalta i Blanch, Jaume
Tàssies Penella, María Dolores
Galan, Ana M.
Diaz Ricart, M. Isabel
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Coagulació sanguínia
Hemostàsia
Assaigs clínics de medicaments
Medicaments
Blood coagulation
Hemostasis
Drug testing
Drugs
topic Coagulació sanguínia
Hemostàsia
Assaigs clínics de medicaments
Medicaments
Blood coagulation
Hemostasis
Drug testing
Drugs
description BACKGROUND: Despite the good safety of rivaroxaban, there is limited information on strategies for urgent reversal of its antihemostatic effects.Methods and Results:Alterations of hemostasis induced by rivaroxaban (230 ng/ml) were assessed by using several tests applied to steady and circulating human blood. Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were measured. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with circulating blood. The potential reversal of prothrombin complex concentrates (PCCs; 50 IU/kg), activated PCCs (aPCCs; 75 IU/kg), or recombinant factor VIIa (rFVIIa; 270 μg/kg) was evaluated. Impairment of TG parameters induced by rivaroxaban were corrected by the different concentrates (aPCC≥PCC>rFVIIa). Prolonged clotting times and reduced clot firmness caused by rivaroxaban on TEM tests were improved by different concentrates (rFVIIa≥aPCC>PCC). Rivaroxaban significantly reduced platelets and fibrin interactions with damaged vascular surfaces in perfusion studies. While alterations of platelet interactions were favourably counteracted by rFVIIa or aPCCs, reductions in fibrin formation were only partially restored by the different factor concentrates (rFVIIa>aPCC≥PCC). CONCLUSIONS: Rivaroxaban-induced alterations on coagulation parameters measured through assays performed under static conditions were easily reversed by the different concentrates. Studies under flow conditions revealed that these concentrates normalized the action of rivaroxaban on platelets, and significantly improved fibrin formation; although in the later case, levels were not restored to the pre-treatment value. (Circ J 2015; 79: 331-338).
publishDate 2015
dc.date.none.fl_str_mv 2015
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/2445/113934
url https://hdl.handle.net/2445/113934
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/10.1253/circj.CJ-14-0909
Circulation Journal, 2015, vol. 79, num. 2, p. 331-338
https://doi.org/10.1253/circj.CJ-14-0909
dc.rights.none.fl_str_mv (c) Japanese Circulation Society, 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Japanese Circulation Society, 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Japanese Circulation Society
publisher.none.fl_str_mv Japanese Circulation Society
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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