What is the role of alloantibody inhibitors in the pathogenesis of hemophilia A?

Updated: Jan 14, 2019
  • Author: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Answer

Approximately 30% of patients with severe hemophilia A develop alloantibody inhibitors that can bind FVIII. These inhibitors are typically immunoglobulin G (IgG), predominantly of the IgG4 subclass, that neutralize the coagulant effects of replacement therapy. However, the inhibitors do not fix complement and do not result in the end-organ damage observed with circulating immune complexes

Inhibitors occur at a young age (about 50% by age 10 years), principally in patients with less than 1% FVIII. Both genetic and environmental factors determine the frequency of inhibitor development. Specific molecular abnormalities (eg, gene deletions, stop codon mutations, frameshift mutations) are associated with a higher incidence of inhibitor development. In addition, inhibitors are more likely to develop in black children. Missense mutations are associated with a low risk of inhibitor development. [7]


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