Severe bleeding diatheses in an elderly patient with combined type autoantibody against factor XIII A subunit; novel approach to the diagnosis and classification of anti-factor XIII antibodies

IntroductionAcquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task.AimIntroduction of novel approaches into the diagnosis and characterization of anti‐FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency.MethodsFactor XIII activity, FXIII antigen levels and the titre of anti‐FXIII‐A antibody were monitored throughout the course of the disease. FXIII activity was measured by ammonia release assay; FXIII‐A2B2 complex, total and free FXIII‐B concentrations were determined by ELISAs. The binding constant for the interaction of the autoantibody with recombinant FXIII‐A2 (rFXIII‐A2) and FXIII‐A2B2 was determined by surface plasmon resonance (SPR). The inhibitory capacity of IgG was expressed as the concentration exerting 50% inhibition of FXIII activation/activity (IC50). The truncation of FXIII‐A by thrombin was monitored by western blotting. The inhibition of Ca2+ ‐induced FXIII activation and active FXIII (FXIIIa) were assessed by FXIII activity assay.ResultsThe antibody bound to rFXIII‐A2 and FXIII‐A2B2 with high affinity and accelerated the decay of supplemented FXIII concentrate. An IC50 value of 170.1 μg IgG·mL−1 indicated effective FXIII neutralization. The main neutralizing effect of the autoantibody was the inhibition of FXIIIa. After 2 months, due to combined therapeutic modalities, the autoantibody disappeared and FXIII activity significantly elevated.ConclusionThe anti‐FXIII‐A autoantibody exerted a combined effect including inhibition of FXIIIa and acceleration of FXIII decay in the plasma. IC50 and binding constant determinations added important information to the characterization of the autoantibody