Figure 1. Fibrinogen and FXIII in hemostasis and venous thrombosis.

(A) FXIII-A- and B-subunits are synthesized in bone marrow and liver, respectively and assembled in plasma. Fibrinogen is also synthesized in the liver. FXIII-A₂B₂ circulates in plasma bound to fibrinogen. FXIII-A₂ also circulates in platelets and leukocytes. (B-C) Vessel injury (hemostasis, B) or endothelial dysfunction associated with blood stasis (venous thrombosis, C) triggers the activation of coagulation and results in the production of thrombin which cleaves fibrinogen into fibrin and activates FXIII to FXIIIa. FXIIIa catalyzes crosslinks between fibrin molecules and between fibrin and antifibrinolytic proteins (i.e., α₂-antiplasmin [α₂-AP]). Crosslinking provides mechanical and biochemical stability to the clot and promotes retention of red blood cells within contracted clots. Controlled clot formation seals the injury site during hemostasis and facilitates wound healing, whereas formation of large intravascular thrombi occludes the vessel and leads to venous thrombosis.