|coagulation factor XIII,
|Locus||Chr. 6 p24.2-p23|
|coagulation factor XIII,
|Locus||Chr. 1 q31-q32.1|
Factor XIII or fibrin stabilizing factor is an enzyme (EC 126.96.36.199) of the blood coagulation system that crosslinks fibrin. Deficiency of this factor (FXIIID) affects clot stability. FXIIID, while generally rare, Iran with 473 cases has the highest global incidence of disorder; the city of Khash has the highest incidence in Iran as it is in sistan and Baluchestan province with high rate of consanguineous marriage.
Factor XIII is a transglutaminase that circulates in the plasma as a heterotetramer of two catalytic A subunits and two carrier B subunits. When thrombin has converted fibrinogen to fibrin, the latter forms a proteinaceous network in which every E-unit is crosslinked to only one D-unit. Factor XIII is activated by thrombin into factor XIIIa; its activation into Factor XIIIa requires calcium as a cofactor. A cleavage by thrombin between residue Arg37 and Gly38 on the N-terminus of the A subunit, leads to the release of the activation peptide (MW 4000 da). In the presence of calcium the carrier subunits dissociate from the catalytic subunits, leading to a 3D change in conformation of factor XIII and hence the exposure of catalytic cysteine residue. Upon activation by thrombin, factor XIIIa acts on fibrin to form γ-glutamyl-Є-lysyl amide cross links between fibrin molecules to form an insoluble clot.
FXIII is known also as Laki-Lorand factor, after Kalman Laki and Laszlo Lorand, the scientists who first proposed its existence in 1948. A 2005 conference recommended standardization of nomenclature.
- A subunit (6p25-p24). The transglutaminase part; this adds an alkyl group to the nitrogen on a glutamine residue, which binds in turn with a lysine on the other chain. The molecular weight of the A chain is approximately 83kDa.
- B subunit (1q31-q32.1). This has no clear enzymatic activity, and may serve as a carrier for the A subunit. The molecular weight of the B chain is approximately 76.5kDa.
Typical concentrations of FXIII in plasma is 10 μg/ml (2A2B heterodimer), while the concentration of free B chain is 22 μg/ml. FXIII has a long half-life, ranging from 5 to 9 days. It is present in plasma, platelets, and monocytes, as well as macrophages and bone marrow precursors of these cell types.
Factor XIII levels are not measured routinely, but may be considered in patients with an unexplained bleeding tendency. As the enzyme is quite specific for monocytes and macrophages, determination of the presence of factor XIII may be used to identify and classify malignant diseases involving these cells.
Dorgalaleh A, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S, et al,. Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis; 2015.
- Dorgalaleh A.*, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S, et al., (2015). "editors. Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis;" 41 (3 (41)): 323–329.
- Laki K, Lóránd L (September 1948). "On the Solubility of Fibrin Clots". Science 108 (2802): 280. doi:10.1126/science.108.2802.280. PMID 17842715.
- Muszbek L, Ariëns RA, Ichinose A (January 2007). "Factor XIII: recommended terms and abbreviations". J. Thromb. Haemost. 5 (1): 181–3. doi:10.1111/j.1538-7836.2006.02182.x. PMID 16938124.