Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients

Background: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Neverthele...

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Autores: Marta-Enguita, Juan, Navarro-Oviedo, Manuel, Muñoz, Roberto, Olier-Arenas, Jorge, Zalba, Guillermo, Lecumberri, Ramón, Mendióroz Iriarte, Maite, Páramo, José A., Roncal Mancho, Carmen, Orbe, Josune
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/56139
Acceso en línea:https://hdl.handle.net/2454/56139
Access Level:acceso abierto
Palabra clave:Ischemic stroke (IS)
Thrombus
Thrombin activatable fibrinolysis inhibitor (TAFI)
Matrix-metalloproteinase 10 (MMP-10)
Hemostasis
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spelling Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patientsMarta-Enguita, JuanNavarro-Oviedo, ManuelMuñoz, RobertoOlier-Arenas, JorgeZalba, GuillermoLecumberri, RamónMendióroz Iriarte, MaitePáramo, José A.Roncal Mancho, CarmenOrbe, JosuneIschemic stroke (IS)ThrombusThrombin activatable fibrinolysis inhibitor (TAFI)Matrix-metalloproteinase 10 (MMP-10)HemostasisBackground: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of hemostatic parameters such as thrombin-activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remains unknown, although their presence could determine thrombus stability and its response to thrombolytic treatment, improving patient’s outcome. Methods: We collected thrombi (n = 45) from large vessel occlusion (LVO) stroke patients (n = 53) and performed a histological analysis of different hemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), and fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, TAFI and VWF activity and recorded clinical variables. Results: In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localized in regions of inflammatory cells, surrounded by erythrocyte and platelet-rich areas, and their content was significantly associated (r = 0.41, p < 0.01). Thrombus TAFI was lower in patients who died during the first 3 months after stroke onset [odds ratio (OR) (95%CI); 0.59 (0.36–0.98), p = 0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r = −0.30, p < 0.05). Besides, VWF was associated with the presence of leukocytes (r = 0.37, p < 0.05), platelets (r = 0.32, p < 0.05), and 3 months mortality [OR (95%CI); 4.5 (1.2–17.1), p = 0.029]. Finally, plasma levels of TAFI correlated with circulating and thrombus platelets, while plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months. Conclusions: The present study suggests that the composition and distribution of thrombus hemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.This work was supported by CIBERCV (CB16/11/00371), Sociedad Española de Trombosis (SETH), project PI19/00065, funded by Instituto de Salud Carlos III and co-funded by UE (FEDER) ‘Una manera de hacer Europa’, and Virto S.A.Frontiers MediaCiencias de la SaludOsasun Zientziak2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2454/56139reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglésinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00065© 2021 Marta-Enguita, Navarro-Oviedo, Muñoz, Olier-Arenas, Zalba, Lecumberri, Mendioroz, Paramo, Roncal and Orbe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/561392026-06-17T12:41:47Z
dc.title.none.fl_str_mv Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
title Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
spellingShingle Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
Marta-Enguita, Juan
Ischemic stroke (IS)
Thrombus
Thrombin activatable fibrinolysis inhibitor (TAFI)
Matrix-metalloproteinase 10 (MMP-10)
Hemostasis
title_short Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
title_full Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
title_fullStr Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
title_full_unstemmed Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
title_sort Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients
dc.creator.none.fl_str_mv Marta-Enguita, Juan
Navarro-Oviedo, Manuel
Muñoz, Roberto
Olier-Arenas, Jorge
Zalba, Guillermo
Lecumberri, Ramón
Mendióroz Iriarte, Maite
Páramo, José A.
Roncal Mancho, Carmen
Orbe, Josune
author Marta-Enguita, Juan
author_facet Marta-Enguita, Juan
Navarro-Oviedo, Manuel
Muñoz, Roberto
Olier-Arenas, Jorge
Zalba, Guillermo
Lecumberri, Ramón
Mendióroz Iriarte, Maite
Páramo, José A.
Roncal Mancho, Carmen
Orbe, Josune
author_role author
author2 Navarro-Oviedo, Manuel
Muñoz, Roberto
Olier-Arenas, Jorge
Zalba, Guillermo
Lecumberri, Ramón
Mendióroz Iriarte, Maite
Páramo, José A.
Roncal Mancho, Carmen
Orbe, Josune
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
dc.subject.none.fl_str_mv Ischemic stroke (IS)
Thrombus
Thrombin activatable fibrinolysis inhibitor (TAFI)
Matrix-metalloproteinase 10 (MMP-10)
Hemostasis
topic Ischemic stroke (IS)
Thrombus
Thrombin activatable fibrinolysis inhibitor (TAFI)
Matrix-metalloproteinase 10 (MMP-10)
Hemostasis
description Background: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of hemostatic parameters such as thrombin-activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remains unknown, although their presence could determine thrombus stability and its response to thrombolytic treatment, improving patient’s outcome. Methods: We collected thrombi (n = 45) from large vessel occlusion (LVO) stroke patients (n = 53) and performed a histological analysis of different hemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), and fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, TAFI and VWF activity and recorded clinical variables. Results: In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localized in regions of inflammatory cells, surrounded by erythrocyte and platelet-rich areas, and their content was significantly associated (r = 0.41, p < 0.01). Thrombus TAFI was lower in patients who died during the first 3 months after stroke onset [odds ratio (OR) (95%CI); 0.59 (0.36–0.98), p = 0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r = −0.30, p < 0.05). Besides, VWF was associated with the presence of leukocytes (r = 0.37, p < 0.05), platelets (r = 0.32, p < 0.05), and 3 months mortality [OR (95%CI); 4.5 (1.2–17.1), p = 0.029]. Finally, plasma levels of TAFI correlated with circulating and thrombus platelets, while plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months. Conclusions: The present study suggests that the composition and distribution of thrombus hemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/2454/56139
url https://hdl.handle.net/2454/56139
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00065
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
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repository.mail.fl_str_mv
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