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Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19
Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. W...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893951/ https://www.ncbi.nlm.nih.gov/pubmed/35235941 http://dx.doi.org/10.1182/bloodadvances.2021006620 |
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author | Henderson, Michael W. Lima, Franciele Moraes, Carla Roberta Peachazepi Ilich, Anton Huber, Stephany Cares Barbosa, Mayck Silva Santos, Irene Palma, Andre C. Nunes, Thyago Alves Ulaf, Raisa Gusso Ribeiro, Luciana Costa Bernardes, Ana Flavia Bombassaro, Bruna Dertkigil, Sergio San Juan Moretti, Maria Luiza Strickland, Sidney Annichino-Bizzacchi, Joyce M. Orsi, Fernanda Andrade Mansour, Eli Velloso, Licio A. Key, Nigel S. De Paula, Erich Vinicius |
author_facet | Henderson, Michael W. Lima, Franciele Moraes, Carla Roberta Peachazepi Ilich, Anton Huber, Stephany Cares Barbosa, Mayck Silva Santos, Irene Palma, Andre C. Nunes, Thyago Alves Ulaf, Raisa Gusso Ribeiro, Luciana Costa Bernardes, Ana Flavia Bombassaro, Bruna Dertkigil, Sergio San Juan Moretti, Maria Luiza Strickland, Sidney Annichino-Bizzacchi, Joyce M. Orsi, Fernanda Andrade Mansour, Eli Velloso, Licio A. Key, Nigel S. De Paula, Erich Vinicius |
author_sort | Henderson, Michael W. |
collection | PubMed |
description | Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor–mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes. |
format | Online Article Text |
id | pubmed-8893951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88939512022-03-04 Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19 Henderson, Michael W. Lima, Franciele Moraes, Carla Roberta Peachazepi Ilich, Anton Huber, Stephany Cares Barbosa, Mayck Silva Santos, Irene Palma, Andre C. Nunes, Thyago Alves Ulaf, Raisa Gusso Ribeiro, Luciana Costa Bernardes, Ana Flavia Bombassaro, Bruna Dertkigil, Sergio San Juan Moretti, Maria Luiza Strickland, Sidney Annichino-Bizzacchi, Joyce M. Orsi, Fernanda Andrade Mansour, Eli Velloso, Licio A. Key, Nigel S. De Paula, Erich Vinicius Blood Adv Thrombosis and Hemostasis Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor–mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes. American Society of Hematology 2022-06-06 /pmc/articles/PMC8893951/ /pubmed/35235941 http://dx.doi.org/10.1182/bloodadvances.2021006620 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://www.ncbi.nlm.nih.gov/pmc/pmcdoc/tagging-guidelines/article/tags.html#el-licenseThis article is made available via the PMC Open Access Subset for unrestricted reuse and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections. |
spellingShingle | Thrombosis and Hemostasis Henderson, Michael W. Lima, Franciele Moraes, Carla Roberta Peachazepi Ilich, Anton Huber, Stephany Cares Barbosa, Mayck Silva Santos, Irene Palma, Andre C. Nunes, Thyago Alves Ulaf, Raisa Gusso Ribeiro, Luciana Costa Bernardes, Ana Flavia Bombassaro, Bruna Dertkigil, Sergio San Juan Moretti, Maria Luiza Strickland, Sidney Annichino-Bizzacchi, Joyce M. Orsi, Fernanda Andrade Mansour, Eli Velloso, Licio A. Key, Nigel S. De Paula, Erich Vinicius Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19 |
title | Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19 |
title_full | Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19 |
title_fullStr | Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19 |
title_full_unstemmed | Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19 |
title_short | Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19 |
title_sort | contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in covid-19 |
topic | Thrombosis and Hemostasis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893951/ https://www.ncbi.nlm.nih.gov/pubmed/35235941 http://dx.doi.org/10.1182/bloodadvances.2021006620 |
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