2003; baxter - Supplements - Haematologica

[New Aspects in Treatment of Hemophilia B Patients]Factor IX mutations andinhibitor development inhemophilia Breview paperhaematologica 2003; 88(suppl. n. 12):75-77http://www.haematologica.org/free/immunotolerance2001.pdfDAVID LILLICRAPDepartments of Pathology and Medicine, Queen’s University,Kingston, Ontario, CanadaThe development of neutralizing antibodies(inhibitors) to the infused therapeutic coagulationprotein in hemophilia represents themost serious therapy-related complicationencountered in the clinical management ofhemophilia. In severe hemophilia A, inhibitorshave been reported in 15-50% of patients surveyedin different populations. 1,2 In contrast, theincidence of anti-factor IX allo-antibody generationin severe hemophilia B patients has beendocumented to be 30 nucleotides),21 patients with factor IX inhibitors are detailed.These 21 patients have eight different factor IXmutations: four different nonsense mutations,three frameshift mutations and a single missensemutation. In addition to the information derivedfrom the Mutation Database, several other studieshave also documented the association of partialor complete factor IX deletion mutations withthe development of inhibitors (Table 1 and Figure1). Thus, as with hemophilia A, the propensityfor inhibitor development is far greater in patientswith factor IX mutations that eliminate or severelydisrupt protein synthesis. In contrast, hemophiliaB patients with missense mutations veryrarely develop inhibitors.This pattern of genotype/phenotype associationis well illustrated by recent studies fromSweden where all of the hemophilia B patientswith inhibitor had either deletion or nonsensehaematologica vol. 88(supplement n. 12):september 2003