Factor XIII is a key molecule at the intersection of coagulation and fibrinolysis as well as inflammation and infection control

Factor XIII (FXIII) is a transglutaminase consisting of two catalytic A subunits (FXIII-A) and two non-catalytic B subunits (FXIII-B) in plasma. FXIII-B protects FXIII-A from its clearance. FXIII-A is also present as a homodimer inside megakaryocytes/platelets and monocytes/macrophages. Although possible functions of intracellular FXIII-A have been proposed, these remain to be established. Intra- and extra-cellular FXIIIs support platelet adhesion and spreading as well as clot retraction, suggesting that FXIII is important for the stabilization of platelet-fibrin clots. Intra- and extra-cellular FXIIIs also support immobilization and killing of bacteria as well as phagocytosis by macrophages. Thus, FXIII may function in innate immunity. Congenital FXIII deficiency due to defective F13-A genes manifests as a life-long bleeding tendency, abnormal wound healing, and recurrent miscarriage. Although congenital FXIII-B deficiency used to be thought rare, reports of such cases have increased recently. As the bleeding tendency is often mild, patients with FXIII-B deficiency may be overlooked by physicians. Patients with acquired FXIII deficiency, in particular those with autoimmune hemorrhaphilia due to anti-FXIII Antibodies, are on the increase, at least in Japan. It is important to diagnose such cases as early as possible, and to treat them with immunosuppression in combination with FXIII replacement therapy as their bleeding symptoms can be life-threatening.