FACTOR-IX INHIBITORS AND ANAPHYLAXIS IN HEMOPHILIA-B

Purpose: We present clinical and laboratory data on 18 children from 1 2 hemophilia treatment centers in the United States, Canada, and Europ e with the purpose of disseminating information regarding a recently r ecognized, potentially life-threatening complication of treatment in v ery young children with hemophilia B. Patients and Methods: Twelve hem ophilia centers from the United States, Canada, and Europe provided cl inical information and laboratory data concerning 18 children who had severe allergic reactions to infused factor (F) IX in close associatio n with the development of an inhibitor to FIX. Laboratory testing for establishment of the diagnosis of hemophilia B and inhibitor to FIX wa s done locally at the centers treating these patients. FIX gene analys is was performed at one of six molecular genetics institutes. Results: All 18 children had severe hemophilia B, and in each an inhibitor ant ibody to FIX developed. The median age at the time of anaphylaxis (or anaphylactoid reaction) was 16 months, and the median number of exposu re days to FIX was 11. The FM inhibitor was detected almost simultaneo usly with the first occurrence of anaphylaxis in 12 of 18 patients. Ma ximum inhibitor titers were 4.5-600 Bethesda units (BU), with a median titer of 48 BU. FIX gene analysis, performed in 17 of 18 patients, de monstrated complete deletion of the FIX gene in 10 and major derangeme nts in seven. Immune tolerance induction (ITI) regimens have been atte mpted in 12 patients, with generally poor responses. Two of the 12 exp erienced nephrotic syndrome while on ITI. Recombinant FVIIa has been s uccessfully used to treat bleeding episodes in 11 of these children. C onclusion: Physicians treating young children with hemophilia B should be aware of the potentially life-threatening complication of anaphyla xis. Children with complete gene deletions or major derangements of th e FIX gene appear to be at greater risk. Those identified by genotype as being at greater risk may need to receive their first 10-20 treatme nts in a medical facility equipped for handling such emergencies. Reco mbinant FVIIa, although not licensed for use in the United States, app ears to be the most suitable treatment option for bleeding episodes in such patients.