title: Immune tolerance therapy for haemophilia A patients with acquired factor VIII alloantibodies: comprehensive analysis of experience at a single institution.
abstract: Immune Tolerance Therapy for Haemophilia A Patients with Acquired Factor VIII Alloantibodies: Comprehensive Analysis of Experience at a Single Institution Eleven children with severe haemophilia A associated with the IVS 22 inversion and acquired high titre neutralising antibodies to factor VIII underwent immune tolerance induction. HLA class I and high resolution class II type is detailed for each patient. A three phase approach to immune tolerance induction was used. During phase 1, which lasted a median of six weeks, patients received factor VIII 100 IU/kg twice daily. Phase 2 comprised a factor VIII dose reduction to 100 IU/kg once daily, and continued for a median duration of 14 weeks. Subsequently 10 of the 11 patients satisfied the criteria of absent factor VIII neutralising activity by the Bethesda method, and a factor VIII elimination half life of greater than 5 h, allowing progression to phase 3, a further factor VIII dose reduction to 50 IU/kg three times weekly. A model for dose reduction as factor VIII tolerance evolves, based on pharmacokinetic analysis, is described.
authors.affiliation: Haemophilia Centre, Reference Centre for Haemostatic and Thrombotic Disorders, St Thomas' Hospital, London, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Smith
authors.forename: K J
authors.initials: KJ
authors.lastname: Spence
authors.forename: E L
authors.initials: EL
authors.lastname: Waters
authors.forename: R
authors.initials: R
authors.lastname: Beresford-Webb
authors.forename: M J
authors.initials: MJ
authors.lastname: Mitchell
authors.forename: J
authors.initials: J
authors.lastname: Cuttler
authors.forename: A
authors.initials: A
authors.lastname: Alhaq
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: G F
authors.initials: GF
authors.lastname: Savidge
mesh_terms: D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D007223:Infant; D007518:Isoantibodies / Q000276:immunology; D008297:Male