ArticleBlood advances2022
Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.Annals of medicine · 2026Article
- Proteomic Analysis of Cerebrospinal Fluid: Toward the Identification of Biomarkers for Early Central Nervous System Infection.Infection and drug resistance · 2026Article
- Activation of the Coagulation Cascade as a Universal Danger Sign.Current issues in molecular biology · 2025Review
- COVID-19: A Disease Driven by Protease/Antiprotease Imbalance? A Specific Review Five Years into the Pandemic.Infection and drug resistance · 2025Review
- Intrinsic pathway activation in patients with antiphospholipid syndrome and healthy controls.Research and practice in thrombosis and haemostasis · 2025Article
- Challenges with measuring tissue factor antigen and activity in human plasma.Blood vessels, thrombosis & hemostasis · 2024Review
- Patterns of C1-Inhibitor Plasma Levels and Kinin-Kallikrein System Activation in Relation to COVID-19 Severity.Life (Basel, Switzerland) · 2024Article
- The Interaction of Complement and Intrinsic Coagulation System: A Comparative Study between COVID-19 and Bacterial Sepsis Patients.Journal of clinical medicine · 2024Article
- Article
- Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus.Cardiovascular diabetology · 2024Review
- Potential Pathways and Pathophysiological Implications of Viral Infection-Driven Activation of Kallikrein-Kinin System (KKS).Viruses · 2024Review
- A novel factor IXa-specific enzyme-linked immunosorbent assay detects factor IXa in human plasma.Research and practice in thrombosis and haemostasis · 2024Article
- Angiopoietin2 is associated with coagulation activation and tissue factor expression in extracellular vesicles in COVID-19.Frontiers in medicine · 2024Article
- COVID-19: Not a thrombotic disease but a thromboinflammatory disease.Upsala journal of medical sciences · 2024Review
- Podoplanin and CLEC-2 levels in patients with COVID-19.Research and practice in thrombosis and haemostasis · 2023Article
- Thrombin formation via the intrinsic coagulation pathway and von Willebrand factor reflect disease severity in COVID-19.Haematologica · 2023Article
- Factor XII contributes to thrombotic complications and vaso-occlusion in sickle cell disease.Blood · 2023Article
- Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.Nature communications · 2023Article
- Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond.Frontiers in physiology · 2023Review
- Association of Ang/Tie2 pathway mediators with endothelial barrier integrity and disease severity in COVID-19.Frontiers in physiology · 2023Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.
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