BACKGROUND: Plasma alpha2-antiplasmin (alpha2AP) is a rapid and effective inhibitor of the fibrinolytic enzyme plasmin. Congenital alpha2AP deficiency results in a severe hemorrhagic disorder due to accelerated fibrinolysis. It is well established that in the presence of thrombin-activated factor XIII (FXIIIa), alpha2AP becomes covalently ligated to the distal alpha chains of fibrin or fibrinogen at lysine 303 (two potential sites per molecule). Some time ago we showed that alpha2AP is covalently linked to plasma fibrinogen . That singular observation led to our hypothesis that native plasma factor XIII (FXIII), which is known to catalyze covalent cross-linking of fibrinogen in the presence of calcium ions, can also incorporate alpha2AP into fibrinogen in the circulation. RESULTS AND CONCLUSIONS: We now provide evidence that FXIII incorporates I 125-labelled alpha2AP into the Aalpha-chain sites on fibrinogen or fibrin. We also measured the content of alpha2AP in isolated plasma fibrinogen fractions by ELISA and found that substantial amounts were present (1.2-1.8 moles per mole fibrinogen). We propose that alpha2AP becomes ligated to fibrinogen while in the circulation through the action of FXIII, and that its immediate presence in plasma fibrinogen contributes to regulation of in vivo fibrinolysis.
BACKGROUND: Plasma alpha2-antiplasmin (alpha2AP) is a rapid and effective inhibitor of the fibrinolytic enzyme plasmin. Congenital alpha2AP deficiency results in a severe hemorrhagic disorder due to accelerated fibrinolysis. It is well established that in the presence of thrombin-activated factor XIII (FXIIIa), alpha2AP becomes covalently ligated to the distal alpha chains of fibrin or fibrinogen at lysine 303 (two potential sites per molecule). Some time ago we showed that alpha2AP is covalently linked to plasma fibrinogen . That singular observation led to our hypothesis that native plasma factor XIII (FXIII), which is known to catalyze covalent cross-linking of fibrinogen in the presence of calcium ions, can also incorporate alpha2AP into fibrinogen in the circulation. RESULTS AND CONCLUSIONS: We now provide evidence that FXIII incorporates I 125-labelled alpha2AP into the Aalpha-chain sites on fibrinogen or fibrin. We also measured the content of alpha2AP in isolated plasma fibrinogen fractions by ELISA and found that substantial amounts were present (1.2-1.8 moles per mole fibrinogen). We propose that alpha2AP becomes ligated to fibrinogen while in the circulation through the action of FXIII, and that its immediate presence in plasma fibrinogen contributes to regulation of in vivo fibrinolysis.
Authors: Sarah von Rappard; Corina Hinnen; Roger Lussmann; Manuela Rechsteiner; Wolfgang Korte Journal: Transfus Med Hemother Date: 2017-03-22 Impact factor: 3.747
Authors: Thomas Walter; Sebastian Szabo; Tim Suselbeck; Martin Borggrefe; Siegfried Lang; Stefanie Swoboda; Hans Martin Hoffmeister; Carl-Erik Dempfle Journal: Clin Drug Investig Date: 2010 Impact factor: 2.859
Authors: N J Mutch; J S Koikkalainen; S R Fraser; K M Duthie; M Griffin; J Mitchell; H G Watson; N A Booth Journal: J Thromb Haemost Date: 2010-09 Impact factor: 5.824