title: Inhibitor development in hemophiliacs: the roles of genetic versus environmental factors.
abstract: Approximately 5 to 7% of patients with hemophilia A have inhibitory antibodies to factor (F) VIII, which increases to approximately 13% in patients with severe disease. The strongest determinant of the risk of inhibitor development identified is the type of mutation in the FVIII gene that gives rise to the disease. However, accumulating evidence clearly indicates that other genetic factors (e.g., major histocompatibility complex alleles and other immune-modulatory genes) and factors associated with treatment (e.g., type of FVIII concentrate, route of administration, and age of first exposure) may also influence the risk of inhibitor development. There is much interest in identifying such genetic and treatment-related factors to help minimize the risk of inhibitor development and improve treatment outcomes.
authors.affiliation: Haemophilia Centre & Haemostasis Unit, Royal Free & University College Medical School, UCL, London, United Kingdom. Christine.Lee@royalfree.nhs.uk
authors.forename: Christine A
authors.initials: CA
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Lillicrap
authors.forename: Jan
authors.initials: J
authors.lastname: Astermark
mesh_terms: D017668:Age of Onset; D000483:Alleles; D019774:Blood Coagulation Factor Inhibitors / Q000737:chemistry / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004777:Environment; D005169:Factor VIII / Q000235:genetics* / Q000276:immunology*; D006467:Hemophilia A / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D012306:Risk; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII