Thromb Haemost 2021; 121(11): 1417-1426
DOI: 10.1055/a-1400-6034
Coagulation and Fibrinolysis

Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19

Stefanie Hammer
1  Center for Clinical Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany
,
Helene Häberle
2  Department of Anaesthesiology and Intensive Care, University Hospital of Tübingen, Tübingen, Germany
,
Christian Schlensak
3  Department of Thoracic, Cardiac and Vascular Surgery, University Hospital of Tübingen, Tübingen, Germany
,
Michael Bitzer
4  Department of Internal Medicine, University Hospital of Tübingen, Tübingen, Germany
,
Nisar P. Malek
4  Department of Internal Medicine, University Hospital of Tübingen, Tübingen, Germany
,
Rupert Handgretinger
5  Children Hospital, University Hospital of Tübingen, Tübingen, Germany
,
Peter Lang
5  Children Hospital, University Hospital of Tübingen, Tübingen, Germany
,
Sebastian Hörber
6  Institute for Clinical Chemistry & Pathobiochemistry, University Hospital Tübingen, Tübingen, Germany
,
Andreas Peter
6  Institute for Clinical Chemistry & Pathobiochemistry, University Hospital Tübingen, Tübingen, Germany
,
Peter Martus
7  Institute of Medical Biometry, University of Tübingen, Tübingen, Germany
,
Valbona Mirakaj
2  Department of Anaesthesiology and Intensive Care, University Hospital of Tübingen, Tübingen, Germany
,
Meinrad Gawaz
8  Department of Internal Medicine III, University Hospital of Tübingen
,
Tobias Geisler
8  Department of Internal Medicine III, University Hospital of Tübingen
,
Karina Althaus
1  Center for Clinical Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany
9  Transfusion Medicine, Medical Faculty of Tübingen, University Hospital of Tübingen, Germany
,
Peter Rosenberger
2  Department of Anaesthesiology and Intensive Care, University Hospital of Tübingen, Tübingen, Germany
,
Tamam Bakchoul
1  Center for Clinical Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany
9  Transfusion Medicine, Medical Faculty of Tübingen, University Hospital of Tübingen, Germany
› Author Affiliations
Funding This work was supported by a research grant from the “Deutsche Herzstiftung,” German Research Foundation (DFG; Project number 374031971–TRR 240) and by the “Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (MWK),” Landesregierung Stuttgart to T.B., H.H., Ch.Sch. and M.G.

Abstract

Background Accumulating evidence indicates toward an association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and procoagulatory state in blood. Thromboelastographic investigations are useful point-of-care devices to assess coagulation and fibrinolysis.

Objectives We investigated the hypothesis that the procoagulatory state in COVID-19 patients is associated with impaired fibrinolysis system.

Methods Altogether, 29 COVID-19 patients admitted to normal wards or to the intensive care unit (ICU) were included in this descriptive study. Whole blood samples were investigated by thromboelastography to assess coagulation and fibrinolysis. Additionally, standard routine coagulation testing and immunoassays for factors of fibrinolysis as plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), plasminogen activity and α2-antiplasmin (A2AP) were performed.

Results A significantly increased lysis resistance and a significantly longer time of lysis after adding tissue plasminogen activator were observed in blood samples from ICU COVID-19 patients compared with healthy controls (maximal lysis: 3.25 ± 0.56 vs. 6.20 ± 0.89%, p = 0.0127; lysis time: 365.7 ± 44.6 vs. 193.2 ± 16.3 seconds, p = 0.0014). PAI-1 activity was significantly higher in plasma samples of ICU COVID-19 patients (PAI-1: 4.92 ± 0.91 vs. 1.28 ± 0.33 U/mL, p = 0.001). A positive correlation between the activity of PAI-1 and lysis time of the formed clot (r = 0.70, p = 0.0006) was observed.

Conclusion Our data suggest that severe SARS-CoV-2 infection is associated with impaired fibrinolytic activity in blood, where fibrinolytic inhibitors are elevated leading to an increased resistance to clot lysis. Thromboelastography could offer a tool to investigate the contribution of the fibrinolytic status to the procoagulatory condition in COVID-19.

Author Contributions

S.H., Ch.Sch., H.H. and T.B. designed the study. S.H., K.A. and A.P. performed the experiments. S.H., K.A., P.M. and T.B. collected and analyzed the laboratory data. S.H., H.H., M.B., R.H., N.P.M., P.L., V.M., T.G., M.G. and T.B. collected and analyzed the clinical data. All authors approved the final version of the manuscript.




Publication History

Received: 17 November 2020

Accepted: 23 February 2021

Publication Date:
25 February 2021 (online)

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