Fibrin film on clots is increased by haematocrit but reduced by inflammation: implications for platelets and fibrinolysis

Ghadir Alkarithi; Cédric Duval; Helen R McPherson; Leander Stewart; Ilaria De Simone; Fraser L Macrae; Robert A S Ariëns

doi:10.1016/j.jtha.2024.12.023

Fibrin film on clots is increased by haematocrit but reduced by inflammation: implications for platelets and fibrinolysis

J Thromb Haemost. 2025 Jan 2:S1538-7836(24)00772-4. doi: 10.1016/j.jtha.2024.12.023. Online ahead of print.

Authors

Ghadir Alkarithi¹, Cédric Duval², Helen R McPherson², Leander Stewart², Ilaria De Simone³, Fraser L Macrae⁴, Robert A S Ariëns²

Affiliations

¹ Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
² Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
³ Department of Data Analysis and Artificial Intelligence & Department of Platelet Pathophysiology & Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands.
⁴ Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK. Electronic address: medfma@leeds.ac.uk.

PMID: 39755330
DOI: 10.1016/j.jtha.2024.12.023

Abstract

Background: Blood clot formation, triggered by vascular injury, is crucial for haemostasis and thrombosis. Blood clots are composed mainly of fibrin fibres, platelets and red blood cells (RBCs). Recent studies show that clot surface also develops 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: Explore the relationship between fibrin films and inflammation, RBC concentration, platelets and fibrinolysis activity.

Patients/methods: We used laser scanning confocal and scanning electron microscopy, ELISA, 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 to control cells. Blood clots formed under conditions of high haematocrit showed significantly more fibrin film coverage than low haematocrit 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.

Conclusions: 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: Fibrinogen; Fibrinolysis; Inflammation; Platelets; Thrombosis.