In non-severe hemophilia A the risk of inhibitor after intensive factor treatment is greater in older patients: a case-control study

J Thromb Haemost. 2010 Oct;8(10):2224-31. doi: 10.1111/j.1538-7836.2010.04013.x.

Abstract

Background: Twenty-five percent of new anti-factor VIII (FVIII) antibodies (inhibitors) that complicate hemophilia A occur in those with mild and moderate disease. Although intensive FVIII treatment has long been considered a risk factor for inhibitor development in those with non-severe disease, its strength of association and the influence of other factors have remained undefined.

Objective: To evaluate risk factors for inhibitor development in patients with non-severe hemophilia A.

Methods: Information on clinical and demographic variables and FVIII genotype was collected on 36 subjects with mild or moderate hemophilia A and an inhibitor and 62 controls also with mild or moderate hemophilia A but without an inhibitor.

Results: Treatment with FVIII for six or more consecutive days during the prior year was more strongly associated with inhibitor development in those ≥30years of age compared with those <30years of age [adjusted odds ratio (OR) 12.62; 95% confidence interval (CI), 2.76-57.81 vs. OR 2.54; 95% CI, 0.61-10.68]. Having previously received <50days of FVIII was also not statistically associated with inhibitor development on univariate or multivariate analysis.

Conclusions: These findings suggest that inhibitor development in mild and moderate hemophilia A varies with age, but does not vary significantly with lifetime FVIII exposure days: two features distinct from severe hemophilia A.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Case-Control Studies
  • Factor VIII / immunology*
  • Factor VIII / therapeutic use
  • Genotype
  • Hemophilia A / blood*
  • Hemophilia A / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation, Missense
  • Risk Factors

Substances

  • Factor VIII