title: Successful immune tolerance induction with high-dose coagulation factor VIII and intravenous immunoglobulins in a patient with congenital hemophilia and high-titer inhibitor of coagulation factor VIII despite unfavorable prognosis for the therapy.
abstract: BACKGROUND
  The production of factor VIII (FVIII) inhibitors is a serious problem of replacement therapy with FVIII concentrates in hemophiliacs. It affects 10-20% patients and leads to an increased risk of severe bleeding and its complications. Immune tolerance induction (ITI) is considered the appropriate treatment in such cases, despite different regimens without clearly defined effectiveness. ITI eradicates FVIII inhibitors and allows retreatment with FVIII concentrates in 70% of patients.
  
  
  METHODS
  The case of a patient with congenital hemophilia A in whom allo-antibodies against FVIII were identified in a high titer at the age of 5 after 70 exposures to human plasma FVIII concentrates is presented. A spontaneous decrease in inhibitor titer to 14 BU/ml within 6 months after the termination of FVIII administration allowed ITI, consisting of FVIII in high doses and intravenous immunoglobulins. Cessation of bleeding during the treatment was achieved with recombinant activated FVII (rFVIIa). ITI lasted for 22 months and, despite the high inhibitor titer at the start of ITI suggesting poor outcome, it led to eradication of the inhibitor. The prophylactic replacement therapy with FVIII was restarted and since then no signs of FVIII inhibitor have been observed.
  
  
  CONCLUSIONS
  ITI with high-dose FVIII, intravenous immunoglobulins, and rFVIIa is a beneficial treatment option for hemophiliac A patients with high-titer FVIII inhibitor.
authors.affiliation: National Hemostasis and Thrombosis Center, Clinic of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine of the Comenius University, Faculty Hospital, Martin, Slovakia. kubisz@jfmed.uniba.sk
authors.forename: Peter
authors.initials: P
authors.lastname: Kubisz
authors.forename: Ivana
authors.initials: I
authors.lastname: Plamenová
authors.forename: Pavol
authors.initials: P
authors.lastname: Hollý
authors.forename: Ján
authors.initials: J
authors.lastname: Stasko
mesh_terms: D019774:Blood Coagulation Factor Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006467:Hemophilia A / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D006487:Hemostasis; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000627:therapeutic use*; D007167:Immunotherapy; D011379:Prognosis; D013997:Time Factors
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D016756:Immunoglobulins, Intravenous; D005169:Factor VIII