Evidence map›Paper›PMID 34183396›Full record

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.

Cédric Duval, Adomas Baranauskas, Tímea Feller, Majid Ali, Lih T Cheah, Nadira Y Yuldasheva, Stephen R Baker, Helen R McPherson, Zaher Raslan, Marc A Bailey and 7 more

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Trial
  2. Review
  3. Open sesame: unlocking mechanics of clots formed under flow.Research and practice in thrombosis and haemostasis · 2026
    Article
  4. Article
  5. Article
  6. Fibrin as a Versatile Fibrous Biopolymer.Sub-cellular biochemistry · 2026
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Fibrin clot properties and thrombus composition in cirrhosis.Research and practice in thrombosis and haemostasis · 2023
    Article
  15. Blood clot contraction: Mechanisms, pathophysiology, and disease.Research and practice in thrombosis and haemostasis · 2023
    Article
  16. Fibrinogen and Factor XIII in Venous Thrombosis and Thrombus Stability.Arteriosclerosis, thrombosis, and vascular biology · 2022
    Review
  17. Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Cédric DuvalLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.ORCID 0000-0002-4870-6542
Adomas BaranauskasLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.
Tímea FellerLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.ORCID 0000-0002-9137-5881
Majid AliLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.
Lih T CheahLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.
Nadira Y YuldashevaLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.
Stephen R BakerLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.ORCID 0000-0002-3147-4925
Helen R McPhersonLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.ORCID 0000-0002-3519-498X
Zaher RaslanLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.
Marc A BaileyLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.
Richard M CubbonLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.ORCID 0000-0001-7844-3600
Simon D ConnellSchool of Physics and Astronomy, University of Leeds, Leeds LS2 3AR, United Kingdom.
Ramzi A AjjanLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.ORCID 0000-0002-1636-3725
Helen PhilippouLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.ORCID 0000-0002-9199-4201
Khalid M NaseemLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom.
Victoria C RidgerDepartment of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom.
Robert A S AriënsLeeds Thrombosis Collective, Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, United Kingdom; R.A.S.Ariens@leeds.ac.uk.ORCID 0000-0002-6310-5745
University of Leeds · GBUniversity of Sheffield · GB

Funding

British Heart Foundation FS/12/80/29821British Heart Foundation FS/18/12/33270British Heart Foundation PG/18/81/34110British Heart Foundation RG/13/3/30104British Heart Foundation RG/18/11/34036British Heart Foundation SI/14/1/30718Wellcome TrustWellcome Trust 208276/Z/17/Z
6 · The paper itself

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.

Indexed as

AnimalsBlood CoagulationBlood PlateletsCross-Linking ReagentsDisease Models, AnimalFactor XIIIaFibrinogenMiceMice, Inbred C57BLOptical ImagingPulmonary EmbolismVena Cava, InferiorVenous ThrombosisCross-Linking ReagentsFactor XIIIaFibrinogenfibrinopeptides gammaclot structureFactor XIIIfibrinmechanical propertiesthromboembolism

Identifiers

PMID34183396
PMCPMC8271579
OpenAlexW3174539853

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.