Immune tolerance therapy for haemophilia A patients with acquired factor VIII alloantibodies: comprehensive analysis of experience at a single institution.

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.

Continuous infusion therapy with very high purity von Willebrand factor concentrate in patients with severe von Willebrand disease.

Five patients with severe (type III) von Willebrand disease received, by continuous infusion, a solvent-detergent treated von Willebrand factor high purity concentrate to control haemostasis. The clinical indications for treatment included prophylaxis prior to orthopaedic, abdominal and tympanic membrane surgery, and treatment of epistaxis and trauma-related bleeding. Plasma vWf antigen and activity were normalized sooner than factor VIII:C levels after initial bolus followed by infusion of the concentrate. Haemostasis was established in all five patients. The degree of shortening of the bleeding time correlated with concentrate infusion rate and, therefore, with administered dose of high molecular weight multimers. Concentrate clearance decreased over time with continued infusion. The product was shown to be stable and sterile at 24 h after reconstitution with no evidence of neoantigen expression. This report illustrates the effectiveness of high purity vWf concentrate administered by continuous infusion and shows that high-molecular-weight multimers are required to shorten the bleeding time to within the normal range.