Evidence map›Paper›PMID 26324704›Full record

ArticleBlood2015

Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking.

James R Byrnes, Cédric Duval, Yiming Wang, Caroline E Hansen, Byungwook Ahn, Micah J Mooberry, Martha A Clark, Jill M Johnsen, Susan T Lord, Wilbur A Lam and 4 more

Abstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

104 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Thrombin kinetics determines robust plasma clot architecture.Research and practice in thrombosis and haemostasis · 2026
    Article
  4. Review
  5. Review
  6. Article
  7. Hypoalbuminemia increases fibrin clot density and impairs fibrinolysis.Journal of thrombosis and haemostasis : JTH · 2026
    Article
  8. Article
  9. Red blood cell-derived transglutaminase 2 influences thrombus formation.Research and practice in thrombosis and haemostasis · 2026
    Article
  10. Fibrin as a Versatile Fibrous Biopolymer.Sub-cellular biochemistry · 2026
    Review
  11. Article
  12. Review
  13. M1 protein from group ABlood vessels, thrombosis & hemostasis · 2025
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Deconstructing fibrin(ogen) structure.Journal of thrombosis and haemostasis : JTH · 2025
    Review
  20. Article

44 more citing papers are in PubMed but not listed here.

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

14 authors.

James R ByrnesDepartment of Pathology and Laboratory Medicine and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC;
Cédric DuvalDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom;
Yiming WangCanadian Blood Services, and Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Canada;
Caroline E HansenSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA; Wallace C. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA;
Byungwook AhnSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA; Wallace C. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA;
Micah J MooberryDepartment of Medicine and.
Martha A ClarkDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC;
Jill M JohnsenResearch Institute, Bloodworks Northwest, Seattle, WA; Department of Medicine, University of Washington, Seattle, WA;
Susan T LordDepartment of Pathology and Laboratory Medicine and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC;
Wilbur A LamSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA; Wallace C. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA;
Joost C M MeijersDepartment of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands.
Heyu NiCanadian Blood Services, and Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Canada;
Robert A S AriënsDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom;
Alisa S WolbergDepartment of Pathology and Laboratory Medicine and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC;ORCID http://orcid.org/0000-0002-2845-2303

Funding

Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
North Carolina Translational & Clinical Sciences Institute (NC TraCS)UL1TR001111 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, CAREY, TIMOTHY S · 2013 to 2017
$43.9M
Duke-UNC Clinical Hematology Research Career Development ProgramK12HL087097 · NHLBI · DUKE UNIVERSITY · PI TELEN, MARILYN J · 2006 to 2016
$4.0M
Cellular Determinants of Fibrin Structure and StabilityR01HL094740 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WOLBERG, ALISA S. · 2009 to 2013
$1.6M
Determinants of Thrombus Structure and StabilityR56HL094740 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WOLBERG, ALISA S. · 2014 to 2014
$378k
British Heart Foundation RG/13/3/30104Medical Research Council G0901546NCATS NIH HHS 1UL1TR001111NCATS NIH HHS UL1 TR001111NCATS NIH HHS UL1 TR002489NHLBI NIH HHS K12 HL087097NHLBI NIH HHS K12HL087097-06NHLBI NIH HHS R01 HL094740NHLBI NIH HHS R01HL094740NHLBI NIH HHS R56 HL094740NHLBI NIH HHS R56HL094740
6 · The paper itself

Abstract

Factor XIII(a) [FXIII(a)] stabilizes clots and increases resistance to fibrinolysis and mechanical disruption. FXIIIa also mediates red blood cell (RBC) retention in contracting clots and determines venous thrombus size, suggesting FXIII(a) is a potential target for reducing thrombosis. However, the mechanism by which FXIIIa retains RBCs in clots is unknown. We determined the effect of FXIII(a) on human and murine clot weight and composition. Real-time microscopy revealed extensive RBC loss from clots formed in the absence of FXIIIa activity, and RBCs exhibited transient deformation as they exited the clots. Fibrin band-shift assays and flow cytometry did not reveal crosslinking of fibrin or FXIIIa substrates to RBCs, suggesting FXIIIa does not crosslink RBCs directly to the clot. RBCs were retained in clots from mice deficient in α2-antiplasmin, thrombin-activatable fibrinolysis inhibitor, or fibronectin, indicating RBC retention does not depend on these FXIIIa substrates. RBC retention in clots was positively correlated with fibrin network density; however, FXIIIa inhibition reduced RBC retention at all network densities. FXIIIa inhibition reduced RBC retention in clots formed with fibrinogen that lacks γ-chain crosslinking sites, but not in clots that lack α-chain crosslinking sites. Moreover, FXIIIa inhibitor concentrations that primarily block α-, but not γ-, chain crosslinking decreased RBC retention in clots. These data indicate FXIIIa-dependent retention of RBCs in clots is mediated by fibrin α-chain crosslinking. These findings expose a newly recognized, essential role for fibrin crosslinking during whole blood clot formation and consolidation and establish FXIIIa activity as a key determinant of thrombus composition and size.

Indexed as

alpha-2-AntiplasminAnimalsBlood CoagulationBlood Coagulation FactorsCarboxypeptidase B2ErythrocytesFibronectinsgamma-GlutamyltransferaseHemorrhagic DisordersHumansMiceMice, Knockoutalpha-2-AntiplasminBlood Coagulation FactorsCarboxypeptidase B2Fibronectinsgamma-Glutamyltransferase

Identifiers

PMID26324704
PMCPMC4608241

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.