Fibrin Factor XIII

Fibrin polymers are responsible for the fibrin-dependent enhancement of Factor XIII activation (Greenberg et al, 2003). The mechanism for this effect involves the formation of a tight ternary complex between fibrin, Factor XIII, and thrombin, accompanied by a conformational change of Factor XIII that exposes the active site, after which Factor XHIa remains bound to fibrin. However, the B chains dissociate, which is necessary to expose the active site cysteine of plasma Factor XIII. Platelet Factor XIII without the B chains, is more rapidly activated by thrombin than plasma Factor XIII because of the time that it takes for the B chains to dissociate. 

Clot formation Fibrinogen Fibrin Factor XIII — F XIU a... 

Factor XIII. Factor XIII circulates in the blood as a zymogen composed of two pairs of different polypeptide chains designated A and B. Inert Factor XIII has a molecular weight of 350,000 daltons and is converted to its active transglutaminase form in the presence of thrombin and calcium. Activated Factor XIII, Xllla, induces an irreversible amide exchange reaction between the y-glutamine and S-lysine side chains of adjacent fibrin... 

Fibrin is formed from fibrinogen synthesized by the liver and secreted into the circulation. The conversion of fibrinogen to fibrin is initiated by a serine protease, thrombin. Thrombin, at the same time, can activate a transglutaminase enzyme, factor XIII present in... 

Fibrinolytics. Figure 2 Various fibrin structures for plasmin. Fibrinogen (Fg) is converted to fibrin (F) by thrombin (T), and thrombin can also convert factor XIII (XIII) to activated factor XIII (Xllla). The latter produces crosslinks between fibrins (FxxF) and also may crosslink fibrin with a2-plasmin inhibitor (FxxFxxPI). The efficiency of digestion of these plasmin substrates by plasmin, resulting in the soluble fibrin degradation products (FDP), is different. The amount of FDP formed in time is expressed in arbitrary units. 

Figure 51-5. Formation of a fibrin clot. A Thrombin-induced cleavage of Arg-Gly bonds of the Aaand B(3 chains of fibrinogen to produce fi-brinopeptides (left-hand side) and the a and p chains of fibrin monomer (right-hand side). B Cross-linking of fibrin molecules by activated factor XIII (factor Xllla).

Activates factor XIII, which strengthens and stabilizes the fibrin meshwork of the clot... 

Fig. 8. Formation of isopeptide bond catalyzed by Factor XHIa. The chemical reaction was catalyzed by Factor XHIa, yielding insoluble fibrin crosslinked by Ne-(7 glutamyl) lysine bonds. Factor XIII is activated to Factor XHIa by thrombin in the presence of calcium ions and fibrin.

Each a chain contains potential glutamine acceptor sites at 221, 237, 328, and 366, and donor sites at lysine 508, 539, 556, 580, and 601 (Greenberg et al., 2003 Matsuka et al., 1996). Since the aC domains associate even in the absence of crosslinking, these interactions probably bring acceptor and donor sites in proximity, facilitating the formation of the isopeptide bonds. These bonds create a covalendy connected network of aC domains, although litde is known of its structure. In addition, there are lesser amounts of 7 trimers, tetramers, and 07 complexes. Factor XIII polymorphisms can have effects on the structure and properties of the fibrin clot (Ariens et al., 2002). 

Lorand, L. (2001). Factor XIII Structure, activation, and interactions with fibrinogen and fibrin. Ann. NY Acad. Sci. 936, 291-311. 

Thrombin activates platelets, converts fibrinogen to fibrin, activates factor XIII, which stabilizes fibrin, and activates factors V and VIE, which accelerate the generation of prothrombinase. Therefore, the inhibition of thrombin is essential in preventing and treating thromboembolic disorders. 

Ariens RAS, Philippou H, Nagaswami C, etal, The FactorXIII V34L polymorphism accelerates thrombin activation of Factor XIII and affects crosslinked fibrin structure, Blood 2000 96 988-995. 

Finally, the common pathway involves thrombin in a number of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a haemostatic plug. In addition, it activates factors VIII and V and their inhibitor protein C (in the presence of thrombomoduhn), and it activates factor XIII, which cross-links the fibrin polymers. 

---