Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study

Blood. 2016 May 12;127(19):2289-97. doi: 10.1182/blood-2015-09-672774. Epub 2016 Feb 24.


Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Disease-Free Survival
  • Factor VIII / antagonists & inhibitors*
  • Female
  • Hemophilia A* / blood
  • Hemophilia A* / mortality
  • Hemophilia A* / therapy
  • Humans
  • Immunoglobulin A / blood*
  • Male
  • Middle Aged
  • Survival Rate


  • Autoantibodies
  • Immunoglobulin A
  • F8 protein, human
  • Factor VIII

Supplementary concepts

  • Factor 8 deficiency, acquired