The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis

BackgroundFactor XIII is a 320kDa tetramer, comprising two enzymatic A-subunits and two carrier B-subunits (FXIII A(2)B(2)). Activated FXIII (FXIIIa) catalyses the formation of epsilon-(-glutamyl)lysyl covalent bonds between -, - and - chains of adjacent fibrin molecules and also cross-links the major plasmin inhibitor, 2-antiplasmin, to fibrin. ObjectivesWe investigated the role of FXIII cross-linking of fibrin directly in clot morphology and its functional effect on clot formation and lysis, in the absence of 2-antiplasmin. Results and ConclusionsOur data show that the presence of FXIII during clot formation results in fibrin clots that have a significant 2.1-fold reduction in pore size, as determined by the Darcy constant, Ks, and formed thinner fibers (74.7 +/- 1.5nm) and higher density of fibers compared with those without FXIII (86.0 +/- 1.7nm, P<0.001), as determined by scanning electron microscopy. Additionally, fibrinolysis showed a significant increase in the time to lysis for clots formed in the presence of FXIII in both static and flow systems. These data demonstrate that independent of 2-antiplasmin, FXIII activity plays a role in increasing the stability of the fibrin clot by altering its structure and increasing the resistance to fibrinolysis.