Thrombomodulin-dependent effect of factor V Leiden mutation on factor XIII activation

Zsuzsa Koncz, Z. Bagoly, G. Haramura, Zoltán A. Mezei, L. Muszbek

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Introduction: Factor V Leiden mutation (FV Leiden) is associated with impaired down-regulation of activated FV procoagulant activity and loss of FV anticoagulant function that result in an increased risk of venous thromboembolism. As the downstream effects of FV Leiden on clot formation and fibrinolyis have only partially been revealed, we investigated its effect on the activation of factor XIII (FXIII) and the cross-linking of fibrin. Methods: In the plasma samples of fifteen healthy individuals with known FV genotypes coagulation was initiated by recombinant human tissue factor and phospholipids with or without recombinant human thrombomodulin (rhTM). FV deficient plasma supplemented with purified wild type FV or FV Leiden were also investigated. Clots were recovered and analyzed by SDS-PAGE and quantitative densitometric evaluation of Western blots. Results: rhTM considerably delayed the activation of FXIII in the plasma from FV wild type individuals. This effect of rhTM was significantly impaired in the plasma from FV Leiden carriers. The results were confirmed in experiments with FV deficient plasma supplemented by FV prepared from wild type individuals or FV Leiden homozygotes. Fibrin γ-chain dimerization was also considerably delayed by rhTM in plasma samples from individuals without Leiden mutation, but not in plasma samples from FV Leiden heterozygotes or homozygotes. The difference between heterozygotes and homozygotes was not statistically significant. Conclusion: The highly diminished delaying effect of TM on FXIII activation and on the cross-linking of fibrin in FV Leiden carriers might represent a novel mechanism contributing to the increased thrombosis risk of these individuals.

Original languageEnglish
Pages (from-to)508-513
Number of pages6
JournalThrombosis Research
Volume129
Issue number4
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Factor XIII
Thrombomodulin
Mutation
Homozygote
Fibrin
Heterozygote
factor V Leiden
Venous Thromboembolism
Dimerization
Thromboplastin
Anticoagulants
Polyacrylamide Gel Electrophoresis
Phospholipids
Thrombosis
Down-Regulation
Western Blotting
Genotype
human THBD protein

Keywords

  • factor V mutation
  • factor XIII
  • fibrin
  • thrombomodulin

ASJC Scopus subject areas

  • Hematology

Cite this

Thrombomodulin-dependent effect of factor V Leiden mutation on factor XIII activation. / Koncz, Zsuzsa; Bagoly, Z.; Haramura, G.; Mezei, Zoltán A.; Muszbek, L.

In: Thrombosis Research, Vol. 129, No. 4, 04.2012, p. 508-513.

Research output: Contribution to journalArticle

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