ArticleJournal of thrombosis and haemostasis : JTH2022
The suboptimal fibrinolytic response in COVID-19 is dictated by high PAI-1.
Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Endotheliopathy in Acute COVID-19 and Long COVID.International journal of molecular sciences · 2023Pooled it
- Subphenotype-specific serum proteomic signatures in patients with ARDS.Journal of intensive care · 2026Article
- Endothelial thrombomodulin-Its role in trauma-induced coagulopathy.Transfusion · 2026Article
- Blood Coagulation in COVID-19: Systems-Biology Evidence, Clinical Implications, and Therapeutic Opportunities in an Evolving Pandemic.ACS omega · 2026Article
- SARS-CoV-2 spike protein can bind fibrin(ogen), but does not alter plasma fibrin formation, clot structure, or lysis.Blood advances · 2026Article
- Immune-endothelial-coagulation crosstalk as a driver of multi-organ dysfunction in severe viral pneumonia.Frontiers in immunology · 2026Review
- Endothelial cell source dictates the expression and release of fibrinolytic markers in a proinflammatory environment.Research and practice in thrombosis and haemostasis · 2025Article
- Acute obstetric coagulopathy is associated with excess plasmin generation and proteolysis of fibrinogen and factor V.Blood advances · 2025Article
- Time series differences in coagulopathy in mechanically ventilated COVID-19 and bacterial pneumonia patients: a nationwide observational study in Japan.Thrombosis journal · 2025Article
- Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook.Seminars in thrombosis and hemostasis · 2025Review
- The endothelial-immunothrombotic storm in viral sepsis: lessons from COVID-19.Frontiers in immunology · 2025Review
- Circulating microRNAs targeting coagulation and fibrinolysis in patients with severe COVID-19.Thrombosis journal · 2024Article
- Persistent hypofibrinolysis in severe COVID-19 associated with elevated fibrinolysis inhibitors activity.Journal of thrombosis and thrombolysis · 2024Article
- The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.Frontiers in immunology · 2024Article
- The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction.Frontiers in immunology · 2024Article
- COVID-19: Not a thrombotic disease but a thromboinflammatory disease.Upsala journal of medical sciences · 2024Review
- Case Report: First attempt by off-label use of tenecteplase to treat acute extensive portal venous system thrombosis.Frontiers in cardiovascular medicine · 2024Article
- Viruses and amyloids - a vicious liaison.Prion · 2023Review
- Changes in the Fibrinolytic System of Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2.Journal of clinical medicine · 2023Article
- Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSevere COVID-19 disease is associated with thrombotic complications and extensive fibrin deposition. This study investigates whether the hemostatic complications in COVID-19 disease arise due to dysregulation of the fibrinolytic system.
methodsThis prospective study analyzed fibrinolytic profiles of 113 patients hospitalized with COVID-19 disease with 24 patients with non-COVID-19 respiratory infection and healthy controls. Antigens were quantified by Ella system or ELISA, clot lysis by turbidimetric assay, and plasminogen activator inhibitor-1 (PAI-1)/plasmin activity using chromogenic substrates. Clot structure was visualized by confocal microscopy.
resultsPAI-1 and its cofactor, vitronectin, are significantly elevated in patients with COVID-19 disease compared with those with non-COVID-19 respiratory infection and healthy control groups. Thrombin activatable fibrinolysis inhibitor and tissue plasminogen activator were elevated in patients with COVID-19 disease relative to healthy controls. PAI-1 and tissue plasminogen activator (tPA) were associated with more severe COVID-19 disease severity. Clots formed from COVID-19 plasma demonstrate an altered fibrin network, with attenuated fiber length and increased branching. Functional studies reveal that plasmin generation and clot lysis were markedly attenuated in COVID-19 disease, while PAI-1 activity was elevated. Clot lysis time significantly correlated with PAI-1 levels. Stratification of COVID-19 samples according to PAI-1 levels reveals significantly faster lysis when using the PAI-1 resistant (tPA) variant, tenecteplase, over alteplase lysis.
conclusionThis study shows that the suboptimal fibrinolytic response in COVID-19 disease is directly attributable to elevated levels of PAI-1, which attenuate plasmin generation. These data highlight the important prognostic potential of PAI-1 and the possibility of using pre-existing drugs, such as tenecteplase, to treat COVID-19 disease and potentially other respiratory diseases.
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