Factor XIII (FXIII, fibrin stabilizing factor) is the proenzyme form of a transamidase that is essential for normal hemostasis and fibrinolysis, wound healing, female fertility and foetal development. Extracellular FXIII consists of A subunits (83 kDa each) which contain the enzyme moiety, and B subunits (76 kDa each) which act as a carrier protein for the A subunit in circulation. Both subunits are produced under separate genetic control. In plasma, FXIII exists as a non-covalent tetrameric complex (320 kDa) of two Asubunits and two B-subunits (A2B2). The concentration of FXIII tetramer in plasma is ~25 micrograms/milliliters (~80 nM). An intracellular form of FXIII is found in platelets, megakaryocytes and monocytes. This form of FXIII presents as a dimer of two A-subunits only and has a molecular weight of 160 kDa. The importance of these intracellular stores is demonstrated by the observation that platelets can contribute up to half of the FXIII activity in platelet rich plasma. The activation of FXIII involves several steps. Thrombin cleaves after Arg³⁷of each A-subunit in the A2B2 tetramer, releasing a 4.5 kDa activation peptide. Additional conformational changes induced by the binding of calcium, and by dissociation of the B-subunits from the A-subunit dimer are required to obtain full enzyme activity. FXIIIa is a cysteine protease that catalyses the formation of gamma-glutamyl-epsilon-lysyl bonds between the gamma and alpha chains of polymerised fibrin molecules. Other proteins found crosslinked into fibrin clots by FXIIIa include fibrinogen, alpha2-antiplasmin, fibronectin, vitronectin and von Willebrand factor.