title: The antifibrinolytic function of factor XIII is exclusively expressed through α₂-antiplasmin cross-linking.
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.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Fraser
authors.forename: Nuala A
authors.initials: NA
authors.lastname: Booth
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Mutch
mesh_terms: D000933:Antifibrinolytic Agents / Q000737:chemistry* / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology*; D025901:Carboxypeptidase B2 / Q000737:chemistry / Q000378:metabolism; D005176:Factor XIII / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D000979:alpha-2-Antiplasmin; D005176:Factor XIII; D025901:Carboxypeptidase B2