Correlation between factor VIII genotype and inhibitor development in hemophilia A

Steven S. Fakharzadeh, Haig H. Kazazian

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


The development of neutralizing antibodies, or inhibitors, against infused factor VIII represents a significant complication of treatment for hemophilia A. Although it is likely that both genetic and environmental factors influence whether patients form inhibitors, correlations between types of factor VIII mutations and inhibitor development are becoming apparent. Approximately 20% of all patients with severe hemophilia A generate inhibitors. Of these inhibitor patients, 90% have inversions, large deletions or nonsense mutations of the factor VIII gene that would be predicted to eliminate production of factor VIII antigen. In contrast to patients with severe disease, inhibitor formation in patients with mild/moderate hemophilia A is rare. Inhibitor patients with mild/moderate disease typically have missense mutations that may cause local conformational changes within immunogenic domains of factor VIII and lead to production of dysfunctional antigen. Taken together, hemophilia A patients are predisposed to inhibitor development with mutations causing infused factor VIII to be perceived as either 1) a completely novel antigen or 2) an immunologically altered antigen.

Original languageEnglish (US)
Pages (from-to)167-171
Number of pages5
JournalSeminars in Thrombosis and Hemostasis
Issue number2
StatePublished - Jul 18 2000
Externally publishedYes


  • Factor VIII gene
  • Factor VIII mutation
  • Hemophilia A
  • Inhibitor

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine


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