Alkarithi, G., Duval, C. orcid.org/0000-0002-4870-6542, McPherson, H.R. et al. (4 more authors) (2025) Fibrin film on clots is increased by hematocrit but reduced by inflammation: implications for platelets and fibrinolysis. Journal of Thrombosis and Haemostasis, 23 (4). pp. 1247-1259. ISSN 1538-7933
Abstract
Background
Blood clot formation, triggered by vascular injury, is crucial for hemostasis and thrombosis. Blood clots are composed mainly of fibrin fibers, platelets, and red blood cells (RBCs). Recent studies show that clot surfaces also develop a fibrin film, which provides protection against wound infection and retains components such as RBCs within the clot. However, the role of fibrin films in thrombi remains poorly understood.
Objectives
To explore the relationship between fibrin films and inflammation, RBC concentration, platelets, and fibrinolysis activity.
Methods
We used laser scanning confocal and scanning electron microscopy, enzyme-linked immunosorbent assay, and turbidity and fibrinolysis assays to investigate the interactions between fibrin film and inflamed endothelium, RBCs, platelets, and fibrinolysis.
Results
We found that plasma clots forming on top of inflamed endothelial cells show less fibrin film coverage and are characterized by higher fiber density and shorter lag time compared with control cells. Blood clots formed under conditions of high hematocrit showed significantly more fibrin film coverage than low hematocrit clots. We found that platelet adhesion was significantly reduced on clots with film compared with clots without film even when platelets were preactivated. Fibrinolysis was faster in clots without film than in clots with film, partly due to reductions in plasmin generation.
Conclusion
Our findings indicate that reductions in fibrin film formation under thromboinflammatory conditions support continued clot growth through effects on increased platelet adhesion and activation. On the other hand, increased fibrin film impairs fibrinolysis. These data show a multifaceted role of the fibrin film in clot growth and stability. Keywords
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | blood platelets; fibrinogen; fibrinolysis; inflammation; thrombosis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 215861/Z/19/Z British Heart Foundation RG/F/23/110112 |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 May 2025 14:37 |
Last Modified: | 20 May 2025 14:37 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jtha.2024.12.023 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:226803 |