title: Successful induction of immune tolerance by continuous infusion of recombinant factor VIII in a haemophilia A patient with high-inhibitor titres.
abstract: The successful and persistent abolition of the inhibitor is of significant clinical benefit, as it allows for the restoration of the usual treatment with clotting factor concentrate. We describe a successful induction of immune tolerance by continuous infusion of recombinant factor VIII (rFVIII) in a 5-year-old boy with severe haemophilia A and high-responding inhibitor. He had previously been subjected to immune tolerance induction (ITI) with rFVIII at 100 units (U) kg(-1) three times weekly. One year after the beginning of therapy tolerance was not achieved and a high titer of inhibitor was detected (15 Bethesda Units). The patient had a sudden onset of severe neck pain. The diagnosis of spinal epidural haematoma was revealed by magnetic resonance imaging, and emergency laminectomy with evacuation of the haematoma was required. The patient received sequential therapy for surgery first as bolus rFVIII injection of 500 U kg(-1) in order to overwhelm the inhibitor and then as continuous infusion at 6 to 12 U kg(-1) hour(-1) to avoid bleeding episodes in the postoperative period. After the 3 weeks of continuous infusion, the inhibitor became undetectable. Thereafter, prophylactic treatment with rFVIII was started three times weekly, and the inhibitor has remained undetectable for 6 months. The, present case suggests that continuous infusion of rFVIII may be an effective therapy to induce immune tolerance.
authors.affiliation: Department of Pediatrics and Developmental Medicine, Gunma University Graduate School of Medicine, Gunma, Japan. ktamura@med.gunma-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Kanazawa
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Shioya
authors.forename: A
authors.initials: A
authors.lastname: Morikawa
mesh_terms: D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D046748:Hematoma, Epidural, Spinal / Q000150:complications / Q000601:surgery; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007262:Infusions, Intravenous; D008297:Male; D016896:Treatment Outcome
chemical_list: C078147:F8 protein, human; D005169:Factor VIII