title: Desensitization and immune tolerance induction in children with severe factor IX deficiency; inhibitors and adverse reactions to replacement therapy: a case-report and literature review.
abstract: Hemophilia B is a rare X-linked recessive disorder with plasma factor IX (FIX) deficiency. 1-3% of patients treated with exogenous FIX-containing products develop inhibitors (i.e. polyclonal high affinity immunoglobulins) that neutralize the procoagulant activity of a specific coagulation factor. Although the incidence of inhibitors in hemophilia B patients is low, most are "high titer" and frequently associated with the development of severe allergic or anaphylactic reactions. Immune tolerance induction as a strategy for inhibitor eradication was first described in 1984. Unfortunately, the overall reported success of immune tolerance induction in FIX deficiency with inhibitors is approximately 25-40%.We report the case of a 2-year-old boy with hemophilia B severe FIX deficiency (<1%), inhibitor antibodies to FIX development, and a history of adverse reactions to FIX infusions, who underwent a successful desensitization and immune tolerance induction with a daily FIX infusion. With this regimen the inhibitor titer decreased with effective bleeding prevention.
authors.affiliation: Department of Pediatrics, University of Udine, Udine, Italy. grandale@libero.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bon
authors.affiliation: Haemophilia Agency, Careggi University Hospital, Florence, Italy. massimo.morfini@unifi.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Morfini
authors.affiliation: Department of Pediatrics, University of Florence, A. Meyer Children's University Hospital, Florence, Italy. a.dini@meyer.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dini
authors.affiliation: Allergy Unit, Department of Pediatrics, University of Florence, A. Meyer Children's University Hospital, Florence, Italy. f.mori@meyer.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mori
authors.affiliation: Allergy Unit, Department of Pediatrics, University of Florence, A. Meyer Children's University Hospital, Florence, Italy. s.barni@meyer.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Barni
authors.affiliation: Haemophilia Centre, "Bianchi-Melacrino-Morelli" Hospital, Reggio Calabria, Italy. gianluca.sattilotta@virgilio.it.
authors.forename: Sottilotta
authors.initials: S
authors.lastname: Gianluca
authors.affiliation: Department of Health Sciences, University of Florence, A. Meyer Children's University Hospital, Florence, Italy. maurizio.demartino@unifi.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: de Martino
authors.affiliation: Allergy Unit, Department of Pediatrics, University of Florence, A. Meyer Children's University Hospital, Florence, Italy. e.novembre@meyer.it.
authors.forename: Elio
authors.initials: E
authors.lastname: Novembre
mesh_terms: D002675:Child, Preschool; D003888:Desensitization, Immunologic; D005164:Factor IX / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002836:Hemophilia B / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D007155:Immunologic Factors; D011994:Recombinant Proteins; D005164:Factor IX