ArticleProceedings of the National Academy of Sciences of the United States of America2021
Elimination of fibrin γ-chain cross-linking by FXIIIa increases pulmonary embolism arising from murine inferior vena cava thrombi.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and stability: Results from a laboratory sub-study of the FEISTY trial.Critical care (London, England) · 2022Trial
- Thrombolytic resistance: an important factor leading to the failure of intravenous thrombolytic therapy.Journal of neurology · 2026Review
- Open sesame: unlocking mechanics of clots formed under flow.Research and practice in thrombosis and haemostasis · 2026Article
- Loss of factor XIII decreases immune cell infiltration and enhances vessel wall endothelialization after venous thrombosis.Blood advances · 2026Article
- Article
- Fibrin as a Versatile Fibrous Biopolymer.Sub-cellular biochemistry · 2026Review
- Review
- Integrated cross-linking by TG2 and FXIII generates hepatoprotective fibrin(ogen) deposits in injured liver.Blood · 2025Article
- Recent Pathophysiological Insights Are Advancing the Treatment of Venous Thromboembolism.JACC. Basic to translational science · 2025Review
- Tougher clots, safer lives? Revisiting the role of factor XIII in thrombus stability and embolization risk.Research and practice in thrombosis and haemostasis · 2025Article
- Fibrinogen αC-region acts as a functional safety latch: Implications for a fibrin biomechanical behaviour model.Acta biomaterialia · 2024Article
- Management of anticoagulation and factor XIII replacement in a patient with severe factor XIII deficiency and recurrent venous thromboembolic disease: case report and review of literature.Research and practice in thrombosis and haemostasis · 2024Article
- Fibrin clot properties in cardiovascular disease: from basic mechanisms to clinical practice.Cardiovascular research · 2023Review
- Fibrin clot properties and thrombus composition in cirrhosis.Research and practice in thrombosis and haemostasis · 2023Article
- Blood clot contraction: Mechanisms, pathophysiology, and disease.Research and practice in thrombosis and haemostasis · 2023Article
- Fibrinogen and Factor XIII in Venous Thrombosis and Thrombus Stability.Arteriosclerosis, thrombosis, and vascular biology · 2022Review
- Cross-linking by tissue transglutaminase-2 alters fibrinogen-directed macrophage proinflammatory activity.Journal of thrombosis and haemostasis : JTH · 2022Article
- Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies.Frontiers in neurology · 2022Review
- Fibrinogen, Fibrin, and Fibrin Degradation Products in COVID-19.Current drug targets · 2022Review
- Novel venous thromboembolism mouse model to evaluate the role of complete and partial factor XIII deficiency in pulmonary embolism risk.Journal of thrombosis and haemostasis : JTH · 2021Article
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
The onset of venous thromboembolism, including pulmonary embolism, represents a significant health burden affecting more than 1 million people annually worldwide. Current treatment options are based on anticoagulation, which is suboptimal for preventing further embolic events. In order to develop better treatments for thromboembolism, we sought to understand the structural and mechanical properties of blood clots and how this influences embolism in vivo. We developed a murine model in which fibrin γ-chain cross-linking by activated Factor XIII is eliminated (FGG3X) and applied methods to study thromboembolism at whole-body and organ levels. We show that FGG3X mice have a normal phenotype, with overall coagulation parameters and platelet aggregation and function largely unaffected, except for total inhibition of fibrin γ-chain cross-linking. Elimination of fibrin γ-chain cross-linking resulted in thrombi with reduced strength that were prone to fragmentation. Analysis of embolism in vivo using Xtreme optical imaging and light sheet microscopy demonstrated that the elimination of fibrin γ-chain cross-linking resulted in increased embolization without affecting clot size or lysis. Our findings point to a central previously unrecognized role for fibrin γ-chain cross-linking in clot stability. They also indirectly indicate mechanistic targets for the prevention of thrombosis through selective modulation of fibrin α-chain but not γ-chain cross-linking by activated Factor XIII to reduce thrombus size and burden, while maintaining clot stability and preventing embolism.
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Registered trials
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