Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with fatal outcome - characterization of the antibody.

Autoantibodies may develop against the catalytic A subunit of factor XIII (FXIII-A) or the carrier B subunit (FXIII-B). Autoimmune FXIII-A deficiency was diagnosed in an elderly (75 years) patient with severe bleeding symptoms. The patient had 3% FXIII activity, and unmeasurable FXIII-A(2)B(2) and FXIII-A antigens in the plasma, whereas, in the platelet lysate, activity and FXIII-A antigen values were normal. As revealed by western blotting, FXIII antigen was present in the plasma, but the autoantibody interfered with the immunoassays. A mixing study indicated the presence of inhibitor with a titer of 63.2 Bethesda units (BU). The patient's IgG bound to FXIII-A(2)B(2) and to FXIII-A(2) with equally high affinity (K-a in the range of 10(9) m(-1)). It exerted a multiple inhibitory effect on FXIII activation/activity (IC50: 50 g mL(-1)). Immunosupressive therapy gradually decreased the autoantibody titer to 8.0 BU, but FXIII activity remained very low, and, owing to recurrent bleeding, the patient died.