Factor XIII

Factor XIII (FXIII) is a protein composed of two catalytic A subunits and two carrier B subunits that circulates in plasma bound to fibrinogen.  When activated, the B subunits dissociate, and activated FXIII (FXIIIa) crosslinks glutamine and lysine residues in α- and γ-chains of fibrin monomers, increasing mechanical stability of the clot.  Additionally, FXIIIa crosslinks antifibrinolytic plasma proteins to the clot, increasing biochemical stability.  We have discovered that FXIII mediates red blood cell retention in clots through fibrin α-chain crosslinking, which in turn mediates clot weight.  We have further shown that FXIII zymogen binds fibrinogen in circulation via residues on the fibrinogen γ-chain.  Consequently, FXIII could be a novel therapeutic target for preventing venous thrombosis.  We are interested in further discerning how FXIII mediates venous thrombosis, as well as evaluating potential anti-thrombotic drugs that target FXIII.

Factor XIII(a) (FXIII[a]) mediates red blood cell (RBC) retention in thrombi. During venous thrombosis (VT), platelets mediate thrombus contraction. FXIII activity increases RBC retention in retracted thrombi (left arrow). If FXIII activity is deficient or activation is delayed, fewer RBCs are retained, resulting in a smaller thrombus (right arrow).

Factor XIIIa mediates red blood cell (RBC) retention in thrombi.

Walton BL, Byrnes JR, Wolberg AS. Fibrinogen, red blood cells, and factor XIII in venous thrombosis. J Thromb Haemost. 2015;13(Suppl. 1):S208-S215.