The antifibrinolytic function of factor XIII is exclusively expressed through α2-antiplasmin cross-linking

Steven R. Fraser, Nuala A. Booth, Nicola J. Mutch

Research output: Contribution to journalArticle

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Abstract

Factor XIII (FXIII) generates fibrin-fibrin and fibrin-inhibitor cross-links. Our flow model, which is sensitive to cross-linking, was used to assess the effects of FXIII and the fibrinolytic inhibitor, α2-antiplasmin (α2AP) on fibrinolysis. Plasma model thrombi formed from FXIII or α2AP depleted plasma lysed at strikingly similar rates, 9-fold faster than pooled normal plasma (PNP). In contrast, no change was observed on depletion of PAI-1 or thrombin activatable fibrinolysis inhibitor (TAFI). Inhibition of FXIII did not further enhance lysis of α2AP depleted thrombi. Addition of PNP to FXIII or α2AP depleted plasmas normalized lysis. Lysis rate was strongly inversely correlated with total cross-linked α2AP in plasma thrombi. Reconstitution of FXIII into depleted plasma stabilized plasma thrombi and normalized γ-dimers and α-polymers formation. However, the presence of a neutralizing antibody to α2AP abolished this stabilization. Our data show that the antifibrinolytic function of FXIII is independent of fibrin-fibrin cross-linking and is expressed exclusively through α2AP.

Original languageEnglish
Pages (from-to)6371-6374
Number of pages4
JournalBlood
Volume117
Issue number23
Early online date6 Apr 2011
DOIs
Publication statusPublished - 9 Jun 2011

Fingerprint

Factor XIII
Antifibrinolytic Agents
Plasmas
Fibrin
Thrombosis
Carboxypeptidase B2
Plasminogen Activator Inhibitor 1
Fibrinolysis
Neutralizing Antibodies
Dimers
Polymers
Stabilization

Keywords

  • fibrin-stabilizing factor
  • ALPHA-2-plasmin inhibitor
  • clot rheology
  • plasma
  • resistance
  • thrombi
  • lysis

Cite this

The antifibrinolytic function of factor XIII is exclusively expressed through α2-antiplasmin cross-linking. / Fraser, Steven R.; Booth, Nuala A.; Mutch, Nicola J.

In: Blood, Vol. 117, No. 23, 09.06.2011, p. 6371-6374.

Research output: Contribution to journalArticle

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AB - Factor XIII (FXIII) generates fibrin-fibrin and fibrin-inhibitor cross-links. Our flow model, which is sensitive to cross-linking, was used to assess the effects of FXIII and the fibrinolytic inhibitor, α2-antiplasmin (α2AP) on fibrinolysis. Plasma model thrombi formed from FXIII or α2AP depleted plasma lysed at strikingly similar rates, 9-fold faster than pooled normal plasma (PNP). In contrast, no change was observed on depletion of PAI-1 or thrombin activatable fibrinolysis inhibitor (TAFI). Inhibition of FXIII did not further enhance lysis of α2AP depleted thrombi. Addition of PNP to FXIII or α2AP depleted plasmas normalized lysis. Lysis rate was strongly inversely correlated with total cross-linked α2AP in plasma thrombi. Reconstitution of FXIII into depleted plasma stabilized plasma thrombi and normalized γ-dimers and α-polymers formation. However, the presence of a neutralizing antibody to α2AP abolished this stabilization. Our data show that the antifibrinolytic function of FXIII is independent of fibrin-fibrin cross-linking and is expressed exclusively through α2AP.

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KW - plasma

KW - resistance

KW - thrombi

KW - lysis

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