Blood Coagulation Factor XIII and Factor XIII Deficiency

Abstract Factor XIII (FXIII) is a multifunctional pro-γ-transglutaminase that, in addition to its well-known role in haemostasis, has a crucial role in angiogenesis, maintenance of pregnancy, wound healing, bone metabolism and even cardio protection. FXIII deficiency (FXIIID) is a Rare Bleeding Disorder (RBD) with an estimated incidence of one per two million that is accompanied by life-threatening bleeding such as umbilical cord bleeding, recurrent spontaneous miscarriage and intracranial hemorrhage (ICH). Today the disease is successfully managed by FXIII concentrate and recombinant FXIII for prophylaxis, management of minor and major bleeding, treatment of ICH and successful delivery in women with recurrent pregnancy loss. Molecular analysis of patients with FXIIID revealed a wide spectrum of mutations, most frequently missense mutations in the FXIII-A subunit, with a few recurrent mutations observed worldwide. In vitro expression studies revealed that most of the missense mutations cause intracellular instability of the FXIII protein and, subsequently, FXIIID.