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Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19.

Whyte, Claire S.; Morrow, Gael B.; Mitchell, Joanne L.; Chowdary, Pratima; Mutch, Nicola J.


Claire S. Whyte

Joanne L. Mitchell

Pratima Chowdary

Nicola J. Mutch


The global pandemic of coronavirus disease 2019 (COVID‐19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID-19 patients show elevated D‐dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID-19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre-existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients.


WHYTE, C.S., MORROW, G.B., MITCHELL, J.L., CHOWDARY, P. and MUTCH, N.J. 2020. Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19. Journal of thrombosis and haemostasis [online], 18(7), pages 1548-1555. Available from:

Journal Article Type Review
Acceptance Date Apr 21, 2020
Online Publication Date Jul 3, 2020
Publication Date Jul 31, 2020
Deposit Date Aug 7, 2023
Publicly Available Date Aug 15, 2023
Journal Journal of thrombosis and haemostasis
Print ISSN 1538-7933
Electronic ISSN 1538-7836
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 18
Issue 7
Pages 1548-1555
Keywords Fibrin; Fibrinolysis; Plasminogen activator inhibitor 1; Respiratory distress syndrome (adult); SARS virus; Tissue plasminogen activator; COVID-19
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WHYTE 2020 Fibrinolytic abnormalities (VOR) (912 Kb)

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Copyright Statement
© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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