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Fibrinolysis in Platelet Thrombi
Rahim Kanji1,2, Ying X Gue3, Vassilios Memtsas2
1Faculty of Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
International Journal of Molecular Sciences
|June 2, 2021
Summary
Clot composition significantly impacts fibrinolysis resistance in atherothrombotic events. High platelet content and specific environmental factors create stable thrombi, hindering clot breakdown and requiring further research into pharmacotherapy effectiveness.
Area of Science:
- Cardiovascular Biology
- Hematology
- Thrombosis Research
Background:
- Arterial atherothrombotic plaque disruption leads to occlusive thrombus formation.
- Endogenous fibrinolysis effectiveness determines thrombus extent and duration.
- Clot composition and formation environment are key determinants of fibrinolysis.
Purpose of the Study:
- To investigate the factors contributing to fibrinolysis resistance in arterial thrombi.
- To understand the role of clot composition, particularly platelet content, in thrombus stability.
- To explore the influence of the microenvironment on thrombus formation and resistance to breakdown.
Main Methods:
- Analysis of thrombus composition, focusing on platelet content and fibrin density.
- Investigation of thrombin generation and fibrinolysis inhibitor release.
- Assessment of environmental factors like high shear stress in coronary stenosis.
- Evaluation of neutrophil extracellular traps and platelet-mediated clot retraction.
- In vitro modeling of pathophysiological conditions.
Main Results:
- High platelet content in thrombi correlates with significant fibrinolysis resistance.
- Augmented thrombin generation and fibrinolysis inhibitor release contribute to stable, fibrin-dense thrombi.
- High shear stress strengthens thrombus attachment in coronary stenosis.
- Neutrophil extracellular traps and platelet retraction enhance fibrinolysis resistance.
- Factor XIII crosslinking further stabilizes thrombi against flow.
Conclusions:
- Platelet-rich thrombi exhibit resistance to endogenous fibrinolysis due to enhanced thrombin generation and inhibitor release.
- Environmental factors and clot structural components like neutrophil extracellular traps and Factor XIII play crucial roles in thrombus stability.
- Further in vitro research is essential to elucidate mechanisms of fibrinolysis resistance and evaluate pharmacotherapies.
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