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Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19
The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. In this study, we determined the altered levels of factor XII (FXII) and its activation products in critically ill patients with COVID-19 in comparison with patients with severe acut...
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/PMC8648369/ https://www.ncbi.nlm.nih.gov/pubmed/34861681 http://dx.doi.org/10.1182/bloodadvances.2021004816 |
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author | Wygrecka, Malgorzata Birnhuber, Anna Seeliger, Benjamin Michalick, Laura Pak, Oleg Schultz, Astrid-Solveig Schramm, Fabian Zacharias, Martin Gorkiewicz, Gregor David, Sascha Welte, Tobias Schmidt, Julius J. Weissmann, Norbert Schermuly, Ralph T. Barreto, Guillermo Schaefer, Liliana Markart, Philipp Brack, Markus C. Hippenstiel, Stefan Kurth, Florian Sander, Leif E. Witzenrath, Martin Kuebler, Wolfgang M. Kwapiszewska, Grazyna Preissner, Klaus T. |
author_facet | Wygrecka, Malgorzata Birnhuber, Anna Seeliger, Benjamin Michalick, Laura Pak, Oleg Schultz, Astrid-Solveig Schramm, Fabian Zacharias, Martin Gorkiewicz, Gregor David, Sascha Welte, Tobias Schmidt, Julius J. Weissmann, Norbert Schermuly, Ralph T. Barreto, Guillermo Schaefer, Liliana Markart, Philipp Brack, Markus C. Hippenstiel, Stefan Kurth, Florian Sander, Leif E. Witzenrath, Martin Kuebler, Wolfgang M. Kwapiszewska, Grazyna Preissner, Klaus T. |
author_sort | Wygrecka, Malgorzata |
collection | PubMed |
description | The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. In this study, we determined the altered levels of factor XII (FXII) and its activation products in critically ill patients with COVID-19 in comparison with patients with severe acute respiratory distress syndrome related to the influenza virus (acute respiratory distress syndrome [ARDS]-influenza). Compatible with those data, we found rapid consumption of FXII in COVID-19 but not in ARDS-influenza plasma. Interestingly, the lag phase in fibrin formation, triggered by the FXII activator kaolin, was not prolonged in COVID-19, as opposed to that in ARDS-influenza. Confocal and electron microscopy showed that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggered formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, clot lysis was markedly impaired in COVID-19 as opposed to that in ARDS-influenza. Dysregulated fibrinolytic system, as evidenced by elevated levels of thrombin-activatable fibrinolysis inhibitor, tissue-plasminogen activator, and plasminogen activator inhibitor-1 in COVID-19 potentiated this effect. Analysis of lung tissue sections revealed widespread extra- and intravascular compact fibrin deposits in patients with COVID-19. A compact fibrin network structure and dysregulated fibrinolysis may collectively contribute to a high incidence of thrombotic events in COVID-19. |
format | Online Article Text |
id | pubmed-8648369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-86483692021-12-07 Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19 Wygrecka, Malgorzata Birnhuber, Anna Seeliger, Benjamin Michalick, Laura Pak, Oleg Schultz, Astrid-Solveig Schramm, Fabian Zacharias, Martin Gorkiewicz, Gregor David, Sascha Welte, Tobias Schmidt, Julius J. Weissmann, Norbert Schermuly, Ralph T. Barreto, Guillermo Schaefer, Liliana Markart, Philipp Brack, Markus C. Hippenstiel, Stefan Kurth, Florian Sander, Leif E. Witzenrath, Martin Kuebler, Wolfgang M. Kwapiszewska, Grazyna Preissner, Klaus T. Blood Adv Thrombosis and Hemostasis The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. In this study, we determined the altered levels of factor XII (FXII) and its activation products in critically ill patients with COVID-19 in comparison with patients with severe acute respiratory distress syndrome related to the influenza virus (acute respiratory distress syndrome [ARDS]-influenza). Compatible with those data, we found rapid consumption of FXII in COVID-19 but not in ARDS-influenza plasma. Interestingly, the lag phase in fibrin formation, triggered by the FXII activator kaolin, was not prolonged in COVID-19, as opposed to that in ARDS-influenza. Confocal and electron microscopy showed that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggered formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, clot lysis was markedly impaired in COVID-19 as opposed to that in ARDS-influenza. Dysregulated fibrinolytic system, as evidenced by elevated levels of thrombin-activatable fibrinolysis inhibitor, tissue-plasminogen activator, and plasminogen activator inhibitor-1 in COVID-19 potentiated this effect. Analysis of lung tissue sections revealed widespread extra- and intravascular compact fibrin deposits in patients with COVID-19. A compact fibrin network structure and dysregulated fibrinolysis may collectively contribute to a high incidence of thrombotic events in COVID-19. American Society of Hematology 2022-02-07 /pmc/articles/PMC8648369/ /pubmed/34861681 http://dx.doi.org/10.1182/bloodadvances.2021004816 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 Wygrecka, Malgorzata Birnhuber, Anna Seeliger, Benjamin Michalick, Laura Pak, Oleg Schultz, Astrid-Solveig Schramm, Fabian Zacharias, Martin Gorkiewicz, Gregor David, Sascha Welte, Tobias Schmidt, Julius J. Weissmann, Norbert Schermuly, Ralph T. Barreto, Guillermo Schaefer, Liliana Markart, Philipp Brack, Markus C. Hippenstiel, Stefan Kurth, Florian Sander, Leif E. Witzenrath, Martin Kuebler, Wolfgang M. Kwapiszewska, Grazyna Preissner, Klaus T. Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19 |
title | Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19 |
title_full | Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19 |
title_fullStr | Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19 |
title_full_unstemmed | Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19 |
title_short | Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19 |
title_sort | altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe covid-19 |
topic | Thrombosis and Hemostasis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648369/ https://www.ncbi.nlm.nih.gov/pubmed/34861681 http://dx.doi.org/10.1182/bloodadvances.2021004816 |
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