Brief report The antifibrinolytic function of factor XIII is exclusively expressed through 2-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, 2antiplasmin (2AP) onfibrinolysis. Plasma model thrombi formed from FXIII or 2AP 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 activatablefibrinolysis inhibitor (TAFI). Inhibition of FXIII did not further enhance lysis of 2AP depleted thrombi. Addition of PNP to FXIII or 2AP depleted plasmas normalized lysis. Lysis rate was strongly inversely correlated with total cross-linked 2AP in plasma thrombi. Reconstitution of FXIII into depleted plasma stabilized plasma thrombi and normalized -dimers and -polymers formation. However, the presence of a neutralizing antibody to 2AP abolished this stabilization. Our data show that the antifibrinolytic function of FXIII is independentoffibrin-fibrincross-linkingand is expressed exclusively through 2AP. (Blood. 2011;117(23):6371-6374)