Research ExplorerPublicationsAltered fibrin clot structure and dysregulated fibrinolysis ...

Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19

Standard

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.

In: BLOOD ADV, Vol. 6, No. 3, 08.02.2022, p. 1074-1087.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wygrecka, M, Birnhuber, A, Seeliger, B, Michalick, L, Pak, O, Schultz, A-S, Schramm, F, Zacharias, M, Gorkiewicz, G, David, S, Welte, T, Schmidt, JJ, Weissmann, N, Schermuly, RT, Barreto, G, Schaefer, L, Markart, P, Brack, MC, Hippenstiel, S, Kurth, F, Sander, LE, Witzenrath, M, Kuebler, WM, Kwapiszewska, G & Preissner, KT 2022, 'Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19', BLOOD ADV, vol. 6, no. 3, pp. 1074-1087. https://doi.org/10.1182/bloodadvances.2021004816

APA

Wygrecka, M., Birnhuber, A., Seeliger, B., Michalick, L., Pak, O., Schultz, A-S., Schramm, F., Zacharias, M., Gorkiewicz, G., David, S., Welte, T., Schmidt, J. J., Weissmann, N., Schermuly, R. T., Barreto, G., Schaefer, L., Markart, P., Brack, M. C., Hippenstiel, S., ... Preissner, K. T. (2022). Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19. BLOOD ADV, 6(3), 1074-1087. https://doi.org/10.1182/bloodadvances.2021004816

Vancouver

Wygrecka M, Birnhuber A, Seeliger B, Michalick L, Pak O, Schultz A-S et al. Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19. BLOOD ADV. 2022 Feb 8;6(3):1074-1087. https://doi.org/10.1182/bloodadvances.2021004816

Bibtex

@article{3868353bf4384353a95b2a4bc0eab743,
title = "Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19",
abstract = "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.",
keywords = "COVID-19, Fibrin, Fibrinolysis, Humans, SARS-CoV-2, Thrombosis/etiology",
author = "Malgorzata Wygrecka and Anna Birnhuber and Benjamin Seeliger and Laura Michalick and Oleg Pak and Astrid-Solveig Schultz and Fabian Schramm and Martin Zacharias and Gregor Gorkiewicz and Sascha David and Tobias Welte and Schmidt, {Julius J} and Norbert Weissmann and Schermuly, {Ralph T} and Guillermo Barreto and Liliana Schaefer and Philipp Markart and Brack, {Markus C} and Stefan Hippenstiel and Florian Kurth and Sander, {Leif E} and Martin Witzenrath and Kuebler, {Wolfgang M} and Grazyna Kwapiszewska and Preissner, {Klaus T}",
note = "{\textcopyright} 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.",
year = "2022",
month = feb,
day = "8",
doi = "10.1182/bloodadvances.2021004816",
language = "English",
volume = "6",
pages = "1074--1087",
journal = "BLOOD ADV",
issn = "2473-9529",
publisher = "Elsevier BV",
number = "3",

}

RIS

TY - JOUR

T1 - Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19

AU - Wygrecka, Malgorzata

AU - Birnhuber, Anna

AU - Seeliger, Benjamin

AU - Michalick, Laura

AU - Pak, Oleg

AU - Schultz, Astrid-Solveig

AU - Schramm, Fabian

AU - Zacharias, Martin

AU - Gorkiewicz, Gregor

AU - David, Sascha

AU - Welte, Tobias

AU - Schmidt, Julius J

AU - Weissmann, Norbert

AU - Schermuly, Ralph T

AU - Barreto, Guillermo

AU - Schaefer, Liliana

AU - Markart, Philipp

AU - Brack, Markus C

AU - Hippenstiel, Stefan

AU - Kurth, Florian

AU - Sander, Leif E

AU - Witzenrath, Martin

AU - Kuebler, Wolfgang M

AU - Kwapiszewska, Grazyna

AU - Preissner, Klaus T

N1 - © 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.

PY - 2022/2/8

Y1 - 2022/2/8

N2 - 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.

AB - 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.

KW - COVID-19

KW - Fibrin

KW - Fibrinolysis

KW - Humans

KW - SARS-CoV-2

KW - Thrombosis/etiology

U2 - 10.1182/bloodadvances.2021004816

DO - 10.1182/bloodadvances.2021004816

M3 - SCORING: Journal article

C2 - 34861681

VL - 6

SP - 1074

EP - 1087

JO - BLOOD ADV

JF - BLOOD ADV

SN - 2473-9529

IS - 3

ER -