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June 28, 2021Proceedings of the National Academy of SciencesOpen Access

Elimination of fibrin γ-chain cross-linking by FXIIIa increases pulmonary embolism arising from murine inferior vena cava thrombi

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Key result

Elimination of fibrin γ-chain cross-linking in FGG3X mice resulted in a 1.5-fold increase in pulmonary emboli count compared to wild-type mice, demonstrating its essential role in clot stability.

Why the study?

Anticoagulation for venous thromboembolism is suboptimal for preventing embolic events, prompting investigation into clot structural and mechanical properties and how they influence in vivo embolism.

Does the elimination of fibrin γ-chain cross-linking by FXIIIa increase pulmonary embolism arising from inferior vena cava thrombi in mice?

Population

Murine model lacking activated Factor XIII fibrin γ-chain cross-linking (FGG3X)

Comparison

Elimination of fibrin γ-chain cross-linking (FGG3X) vs normal phenotype

Design

Preclinical animal study

Authors

CDCédric DuvalABAdomas BaranauskasTFTímea Feller

Discussion

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Member takes

Overview

Supports fibrin cross-linking for clot stability in mice; leaves open whether FXIIIa targeting affects human thromboembolism risk.

Structured PICO

Does the elimination of fibrin γ-chain cross-linking by FXIIIa increase pulmonary embolism arising from inferior vena cava thrombi in mice?

P
Population
Genetically modified FGG3X mice and wild-type mice aged 6 to 8 weeks were evaluated to determine the role of fibrin γ-chain cross-linking in clot stability and pulmonary embolism.
E
Exposure
Elimination of fibrin γ-chain cross-linking by FXIIIa (FGG3X mutation)
C
Comparator
Wild-type (WT) mice
O
Outcome
Embolic events (pulmonary embolism) arising from inferior vena cava thrombi in vivosurrogate

Main Result

Effect estimate: 1.5-fold increase

p-value: p=<0.001

Elimination of fibrin γ-chain cross-linking reduces clot stability and increases pulmonary embolism in a murine model, highlighting its critical role in preventing thromboembolism.

Limitations

  • Optical imaging intensity measurements do not provide detailed information on the number and volume of the emboli or their precise location within the lungs.
  • Light sheet microscopy is a terminal procedure, requiring a larger number of animals if more than one time point is required.

Cite This Study

Duval et al. (2021) studied Venous thromboembolism and pulmonary embolism. FGG3X mutation (elimination of fibrin γ-chain cross-linking) vs. Wild-type mice was evaluated on Pulmonary emboli count (1.5-fold increase, p=<0.001). Elimination of fibrin γ-chain cross-linking in FGG3X mice resulted in a 1.5-fold increase in pulmonary emboli count compared to wild-type mice, demonstrating its essential role in clot stability.

synapsesocial.com/papers/6a8441ba9c756a6796f2f2fbhttps://doi.org/10.1073/pnas.2103226118
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Is dual targeting of FXII and Gas6 a good strategy to prevent thrombosis with no risks of bleeding?2025
  2. 2Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRγ deficiency2006 · 145 citations
  3. 3Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis2022 · 39 citations
  4. 4Fibrin-bound thrombin determines clot structure and blood thrombogenicity in normofibrinogenemia and dysfibrinogenemia2026 · 1 citations
  5. 5Glycoprotein VI–dependent and –independent pathways of thrombus formation in vivo2006 · 228 citations