FXIIIA

FXIIIa is the activated form of coagulation Factor XIII, a calcium-dependent transglutaminase that cross-links fibrin to stabilize blood clots. It is produced as part of the circulating heterotetramer FXIII-A2B2, composed of two catalytic A subunits (FXIII-A) and two carrier B subunits (FXIII-B). In the coagulation cascade, thrombin cleaves an activation peptide from the A subunits, and in the presence of calcium the B subunits dissociate, yielding the active enzyme FXIIIa, an A2 dimer, that covalently cross-links fibrin and other substrates within the clot.

FXIIIa catalyzes the formation of ε-(γ-glutamyl)lysine isopeptide bonds between glutamine and lysine residues. In fibrin, this results in cross-linking of fibrin chains (notably alpha and gamma chains), which increases clot stiffness and resistance to fibrinolysis. FXIIIa also cross-links other components of the clot and surrounding matrix, including alpha2-antiplasmin, fibronectin, and collagen, contributing to wound stabilization and tissue repair.

Physiologically, FXIIIa plays a key role in ensuring clot integrity under mechanical and proteolytic stress. Deficiency or dysfunction of FXIII leads to a bleeding tendency that is often not detected by standard coagulation tests such as prothrombin time or activated partial thromboplastin time; routine screening may miss isolated FXIII impairment. Congenital FXIII deficiency is rare and typically inherited in an autosomal recessive pattern, caused by defects in F13A1 (the A subunit) or F13B (the B subunit). Diagnosis relies on specific FXIII activity assays, and treatment involves FXIII concentrate or, in some settings, fresh frozen plasma.