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Thromb Haemost 2014; 111(05): 842-850
DOI: 10.1160/TH13-10-0855
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Roles of fibrin α- and γ-chain specific cross-linking by FXIIIa in fibrin structure and function

Cédric Duval
1   Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics and Multidisciplinary Cardiovascular Research Centre, Faculty of Medicine and Health, University of Leeds, UK
,
Peter Allan
1   Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics and Multidisciplinary Cardiovascular Research Centre, Faculty of Medicine and Health, University of Leeds, UK
2   Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, UK
,
Simon D. A. Connell
2   Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, UK
,
Victoria C. Ridger
3   Department of Cardiovascular Science, Faculty of Medicine, Dentistry, and Health, University of Sheffield, UK
,
Helen Philippou
1   Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics and Multidisciplinary Cardiovascular Research Centre, Faculty of Medicine and Health, University of Leeds, UK
,
Robert A. S. Ariëns
1   Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics and Multidisciplinary Cardiovascular Research Centre, Faculty of Medicine and Health, University of Leeds, UK
› Author Affiliations Financial support: This study was supported by Medical Research Council (G0901546) and British Heart Foundation (RG/13/2/30104) grants.
Further Information

Publication History

Received: 16 October 2013

Accepted after major revision: 11 January 2013

Publication Date:
01 December 2017 (online)

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Summary

Factor XIII is responsible for the cross-linking of fibrin γ-chains in the early stages of clot formation, whilst α-chain cross-linking occurs at a slower rate. Although γ- and α-chain cross-linking was previously shown to contribute to clot stiffness, the role of cross-linking of both chains in determining clot structure is currently unknown. Therefore, the aim of this study was to determine the role of individual α- and γ-chain cross-linking during clot formation, and its effects on clot structure. We made use of a recombinant fibrinogen (γQ398N/Q399N/K406R), which does not allow for y-chain cross-linking. In the absence of cross-linking, intact D-D interface was shown to play a potential role in fibre appearance time, clot stiffness and elasticity. Cross-linking of the fibrin α-chain played a role in the thickening of the fibrin fibres over time, and decreased lysis rate in the absence of α2-antiplasmin. We also showed that α-chain cross-linking played a role in the timing of fibre appearance, straightening fibres, increasing clot stiffness and reducing clot deformation. Cross-linking of the γ-chain played a role in fibrin fibre appearance time and fibre density. Our results show that α- and γ-chain cross-linking play independent and specific roles in fibrin clot formation and structure.

Keywords

Fibrinogen - factor XIII - clot structure

 

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