Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19
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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, Jahrgang 6, Nr. 3, 08.02.2022, S. 1074-1087.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -