Case Report: Development of Factor VIII Inhibitor in a Patient with an Uncommon de novo Mutation in the Factor VIII Gene

Acta Haematol. 2019;141(3):129-134. doi: 10.1159/000495559. Epub 2019 Feb 15.

Abstract

The development of factor VIII inhibitors remains a significant clinical challenge in the management of hemophilia A. We present a patient of mixed ethnicity with severe hemophilia A who was found to have a F8 gene hemizygous c.5815G>T mutation resulting in an Ala1939Ser substitution (Ala1920Ser in legacy nomenclature) and possible splice site change that has been reported in only 1 patient previously. He developed an inhibitor shortly after starting replacement recombinant factor VIII (Advate®; Baxalta, Bannockburn, IL, USA) and was successfully treated with immune tolerance therapy. Our report describes the second patient reported to have severe hemophilia due to this mutation and the only case of a factor VIII inhibitor associated with this mutation.

Keywords: Hemophilia A; Immune tolerance therapy; Inhibitor.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Blood Coagulation Factor Inhibitors / blood*
  • Factor VIII* / administration & dosage
  • Factor VIII* / genetics
  • Hemophilia A* / blood
  • Hemophilia A* / drug therapy
  • Hemophilia A* / genetics
  • Humans
  • Infant, Newborn
  • Male
  • Mutation, Missense*

Substances

  • Blood Coagulation Factor Inhibitors
  • F8 protein, human
  • Factor VIII