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

Blood. 2011 Jun 9;117(23):6371-4. doi: 10.1182/blood-2011-02-333203. Epub 2011 Apr 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifibrinolytic Agents / chemistry*
  • Antifibrinolytic Agents / metabolism
  • Blood Coagulation / physiology*
  • Carboxypeptidase B2 / chemistry
  • Carboxypeptidase B2 / metabolism
  • Factor XIII / chemistry*
  • Factor XIII / metabolism
  • Humans
  • Models, Chemical*
  • Plasminogen Activator Inhibitor 1 / chemistry
  • Plasminogen Activator Inhibitor 1 / metabolism
  • alpha-2-Antiplasmin / chemistry*
  • alpha-2-Antiplasmin / metabolism

Substances

  • Antifibrinolytic Agents
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • alpha-2-Antiplasmin
  • Factor XIII
  • Carboxypeptidase B2