Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population

Haemophilia. 2019 Jan;25(1):67-74. doi: 10.1111/hae.13633. Epub 2018 Nov 14.

Abstract

Introduction: Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors.

Aim: To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it.

Methods: Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters.

Results: Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High-titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1-13-positive cases (RR = 2.04; 95% CI 1.06-3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high-titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4-590 C/T allele (RR = 0.22; 95% CI 0.108-0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study.

Conclusion: The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross-sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.

Keywords: environmental; genetic; haemophilia; inhibitors; risk factors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Child
  • Child, Preschool
  • Factor VIII / antagonists & inhibitors*
  • Haplotypes
  • Hemophilia A / epidemiology
  • Hemophilia A / pathology*
  • Humans
  • India / epidemiology
  • Interleukin-4 / genetics
  • Isoantibodies / blood*
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Prothrombin Time
  • Young Adult

Substances

  • IL4 protein, human
  • Isoantibodies
  • Interleukin-4
  • Factor VIII