Background: Acquired hemophilia A (AHA) is a potentially life-threatening bleeding disorder caused by factor VIII (FVIII) autoantibodies, involving various immunoglobulin (Ig) isotypes and IgG subclasses.
Objectives: We analyzed the profile of Ig against FVIII in patients with AHA to identify Ig patterns predictive of bleeding phenotype and outcomes.
Patients/methods: Ig detection and titration were determined by enzyme-linked immunosorbent assay (ELISA) at disease presentation in a cohort of 66 subjects from the Quebec Reference Centre for Inhibitors registry.
Results: Most of plasma samples analyzed (97%) contained multiple anti-FVIII Ig isotypes and IgG subclasses, IgG(1,2,3,4) (24.2%), [IgG(1,2,3,4),IgA] (16.7%) and IgG(2.4) (13.6%) being the most prevalent combinations of Ig detected. AHA patients who presented with IgA antibodies were more likely to have an associated auto-immune disease (p = .049). The presence of IgG4-was associated with bleeding symptoms at presentation (p = .002). IgG1-positive patients were more likely to require transfusions with red packed cell (p = .014) whereas IgM detection was associated with a higher probability of death linked to AHA (p = .011).
Conclusion: The Ig pattern of AHA patients at diagnosis is widely heterogeneous and is at least partially associated with some underlying conditions. Our data supports the differential predictive significance for IgG1, IgG4 and IgM on bleeding severity and suggests that the early determination of Ig profile may help to identify AHA patients at higher risk of poorer outcomes.
Keywords: Bethesda assay; ELISA; acquired hemophilia A; factor VIII; immunoglobulin; inhibitor.
© 2021 International Society on Thrombosis and Haemostasis.