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

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, alpha(2)-antiplasmin (alpha(2)AP) on fibrinolysis. Plasma model thrombi formed from FXIII or alpha(2)AP 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 alpha(2)AP depleted thrombi. Addition of PNP to FXIII or alpha(2)AP depleted plasmas normalized lysis. Lysis rate was strongly inversely correlated with total cross-linked alpha(2)AP in plasma thrombi. Reconstitution of FXIII into depleted plasma stabilized plasma thrombi and normalized gamma-dimers and alpha-polymers formation. However, the presence of a neutralizing antibody to alpha(2)AP abolished this stabilization. Our data show that the antifibrinolytic function of FXIII is independent of fibrin-fibrin cross-linking and is expressed exclusively through alpha(2)AP. (Blood. 2011; 117(23): 6371-6374)