Blood factor XIII

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... 

Cryoprecipitate Component of blood obtained by freezing and thawing plasma that is rich in clotting factors. One unit of cryoprecipitate derived from a unit of whole blood contains a volume of 10 to 20 mL, 80 to 100 units of factor VIII which consists of both the procoagulant activity and the von Willebrand factor, 150 to 250 mg of fibrinogen, 50 to 100 units of factor XIII, and 50 to 60 mg of fibronectin. 

Lee, K.Y., Birckbichler, P.J., and Patterson Jr., M.K. (1988) Colorimetric assay of blood coagulation factor XIII in plasma. Clin. Chem. 34, 906-910. 

A (very rare) genetic deficiency in the production of factor XIII also results in impaired clotting efficacy in affected persons. In this case, covalent links that normally characterize transformation of a soft clot into a hard clot are not formed. Factor XIII preparations, partially purified from human blood, are used to treat individuals with this condition to date, no recombinant version of the product has been commercialized. 

Greenberg, C. S., Miraglia, C. C., Rickies, F. R., and Shuman, M. A. (1985). Cleavage of blood coagulation factor XIII and fibrinogen by thrombin during in vitro clotting. J. Clin. Invest. 75, 1463—1470. 

Muszbeck L, Adany R, Mikkola H. Novel aspects of blood coagulation Factor XIII. Structure, distribution, activation and function. Crit Rev Clin Lab Sci 1996 33 357-421. 

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. 

As the basis for decisions about the first dosing in humans, the preclinical safety program needs to mimic the intended clinical regimen. Although these studies are commonly conducted in normal healthy animals, they may also require development and use of an animal model that mimics the health status or condition if it is deemed to possibly sensitize the subject to treatment. For example, we have conducted studies evaluating the safety of recombinant human Factor XIII in an animal model of extracorporeal blood circulation [6] and the safety of recombinant human thrombin in an animal model of hepatic resection [7]. 

Ponce R, Armstrong K, Andrews K, Hensler J, Waggie K, Heffernan J, Reynolds T, Rogge M. Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation. Toxicol Pathol 2005 33(6) 702-10. 

Figure 5.3. Intrinsic and extrinsic blood clotting cascades. Factor I, fibrinogen Factor II, prothrombin (vitamin K-dependent) Factor III, thromboplastin Factor V, proac-celerin Factor VII, proconvertin (vitamin K-dependent) Factor VIII, antihemophilic factor Factor IX, Christmas factor (vitamin K-dependent) Factor X, Stnart factor (vitamin K-dependent) Factor XI, plasma thromboplastin Factor XII, Hageman factor Factor XIII, fibrin-stabilizing factor and Factor XIV, protein C (vitamin K-dependent). What was at one time called Factor IV is calcinm no factor has been assigned nnmber VI.

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