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Mismatched Protein Can Hinder Hemophilia Therapy

Last Updated: April 15, 2009.

Mismatched factor VIII proteins used in infusion therapy in black hemophiliacs increase the likelihood of producing inhibitors that can neutralize the treatment, according to a study reported in the April 16 issue of the New England Journal of Medicine.

WEDNESDAY, April 15 (HealthDay News) -- Mismatched factor VIII proteins used in infusion therapy in black hemophiliacs increase the likelihood of producing inhibitors that can neutralize the treatment, according to a study reported in the April 16 issue of the New England Journal of Medicine.

Kevin R. Viel, Ph.D., of the Southwest Foundation for Biomedical Research in San Antonio, and colleagues sequenced the factor VIII gene in 78 black patients with hemophilia A looking for the mutations and the haplotypes where they were located to identify associations with those factors and the development of inhibiting alloantibodies that can neutralize factor VIII infusion therapy. The researchers also looked at other patient characteristics such as age, disease severity and genetic relationships, and used multivariable logistic regression to control for confounding variables.

The investigators found that patients in the study group with mutations in the H3 or H4 background haplotype (haplotypes unique to blacks) had a higher prevalence of inhibitors than study participants with mutations in H1 or H2 haplotypes (found in both whites and blacks). The odds of having factor VIII inhibitors among patients with H3 or H4 haplotype mutations were significantly higher versus those with H1 or H2 haplotype, even after adjustment for variables (odds ratio, 3.6), the researchers report.

"We acknowledge that our study has limited statistical power because of the small number of patients and that the results require confirmation. The importance of independent replication is that it would strengthen the evidence that mismatched factor VIII replacement proteins are a risk factor for the development of inhibitors," the authors write.

Several authors report a financial relationship with the pharmaceutical industry.

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