Recombinant factor XIII and congenital factor XIII deficiency: an update from human and animal studies

Abstract:

Factor XIII (FXIII) is a protransglutaminase composed of two catalytic A subunits and two carrier B subunits. An intracellular form of FXIII is present in monocytes/macrophages and platelets as a homodimer of two A subunits. Following activation by thrombin, FXIII becomes plasma transglutaminase, which crosslinks γ-glutamyl-ε-lysine residues of fibrin chains and thereby stabilizes the fibrin clot. FXIII deficiency results in a moderate to severe hemorrhagic disorder, abnormal wound healing in about 30% of patients, and recurrent abortion in homozygous females. More than 800 cases of FXIII deficiency have been reported, most of them due to mutation in the FXIII-A gene, resulting in FXIII-A deficiency. Among mutations causing FXIII-A deficiency, 50% are missense mutations. Only 16 mutations in the FXIII-B gene have been published. Routine laboratory tests are normal in patients with FXIII deficiency, and the diagnosis is established by demonstration of decreased FXIII activity and antigen. Plasma-derived, virus-inactivated factor XIII concentrate is the treatment of choice. The low plasma levels of FXIII (about 5%) required to control bleeding and its long half-life make monthly prophylactic therapy feasible. Recently, recombinant FXIII concentrate with a half-life similar to that of native FXIII has been developed and tested in a multinational clinical study. This new product appears to be safe and appropriate for lifelong prophylactic treatment of patients with FXIII-A deficiency.

Keywords::

• recombinant FXIII concentrate
• FXIII deficiency