ReviewJournal of thrombosis and haemostasis : JTH2020
Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19.
Review in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04466670 (Dynamics of Hemostatic Parameters in COVID-19 and Comparison of Intervention Strategies Through Adaptive Clinical Trial), which is not on this map. Cited by 170 papers, 8 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Dynamics of Hemostatic Parameters in COVID-19 and Comparison of Intervention Strategies Through Adaptive Clinical Trial
Who cites it
170 citing papers in PubMed, 8 syntheses or guidelines pooled it, 277 citations in OpenAlex.
- Vascular Complications of Long COVID-From Endothelial Dysfunction to Systemic Thrombosis: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Endotheliopathy in Acute COVID-19 and Long COVID.International journal of molecular sciences · 2023Pooled it
- Tissue factor in COVID-19-associated coagulopathy.Thrombosis research · 2022Pooled it
- Innate immunity to SARS-CoV-2 infection: a review.Epidemiology and infection · 2022Pooled it
- Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: A systematic review and meta-analysis.Microvascular research · 2021Pooled it
- Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients.Scientific reports · 2021Pooled it
- Clinical determinants of the severity of COVID-19: A systematic review and meta-analysis.PloS one · 2021Pooled it
- Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review.Critical care (London, England) · 2020Pooled it
- Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study.Pharmacological research · 2020Trial
- SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Risk factors and clinical characteristics of fulminant Mycoplasma pneumoniae pneumonia in children: a retrospective case‒control study.BMC infectious diseases · 2026Article
- ALKBH5-Driven m6A Demethylation Boosts Inflammation and Autophagy in LPS-Stimulated Macrophages.Immunity, inflammation and disease · 2026Article
- Concomitant use of sivelestat sodium hydrate and antithrombotic drugs worsens the treatment outcome of patients with acute respiratory distress syndrome and suppression of fibrinolysis: a single-center, retrospective study.Fujita medical journal · 2025Article
- First-in-human Evaluation of Safety and Dosimetry of [Molecular imaging and biology · 2025Article
- Neutrophil extracellular traps in tumor metabolism and microenvironment.Biomarker research · 2025Review
- Nebulized alteplase in coronavirus disease 2019 pneumonia: a case series.Journal of medical case reports · 2024Article
- Alteplase in COVID-19 severe hypoxemic respiratory failure: the TRISTARDS multicenter randomized trial.Annals of intensive care · 2024Article
- Dosimetry of [medRxiv : the preprint server for health sciences · 2024Article
- The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients.Scientific reports · 2024Article
- Diabetes Mellitus, Energy Metabolism, and COVID-19.Endocrine reviews · 2024Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.