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

Background: Factor XIII is a 320 kDa tetramer, comprising two enzymatic A‐subunits and two carrier B‐subunits (FXIII A2B2). Activated FXIII (FXIIIa) catalyses the formation of ε‐(γ‐glutamyl)lysyl covalent bonds between γ‐γ, γ‐α and α‐α chains of adjacent fibrin molecules and also cross‐links the major plasmin inhibitor, α2‐antiplasmin, to fibrin. Objectives: We 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 α2‐antiplasmin. Results and Conclusions: Our 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 ± 1.5 nm) and higher density of fibers compared with those without FXIII (86.0 ± 1.7 nm, 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 α2‐antiplasmin, FXIII activity plays a role in increasing the stability of the fibrin clot by altering its structure and increasing the resistance to fibrinolysis.