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Factor IX inhibitors and anaphylaxis in hemophilia B

Warrier, Indira; Ewenstein, Bruce M.; Koerper, Marion A.; Shapiro, Amy; Key, Nigel; DiMichele, Donna; Miller, Robert T.; Pasi, John; Rivard, Georges E. and Sommer, Steve S., et al. (1997) In Journal of Pediatric Hematology/Oncology 19(1). p.23-27
Abstract

Purpose: We present clinical and laboratory data on 18 children from 12 hemophilia treatment centers in the United States, Canada, and Europe with the purpose of disseminating information regarding a recently recognized, potentially life-threatening complication of treatment in very young children with hemophilia B. Patients and Methods: Twelve hemophilia centers from the United States, Canada, and Europe provided clinical information and laboratory data concerning 18 children who had severe allergic reactions to infused factor (F) IX in close association with the development of an inhibitor to FIX. Laboratory testing for establishment of the diagnosis of hemophilia B and inhibitor to FIX was done locally at the centers treating these... (More)

Purpose: We present clinical and laboratory data on 18 children from 12 hemophilia treatment centers in the United States, Canada, and Europe with the purpose of disseminating information regarding a recently recognized, potentially life-threatening complication of treatment in very young children with hemophilia B. Patients and Methods: Twelve hemophilia centers from the United States, Canada, and Europe provided clinical information and laboratory data concerning 18 children who had severe allergic reactions to infused factor (F) IX in close association with the development of an inhibitor to FIX. Laboratory testing for establishment of the diagnosis of hemophilia B and inhibitor to FIX was done locally at the centers treating these patients. FIX gene analysis was performed at one of six molecular genetics institutes. Results: All 18 children had severe hemophilia B, and in each an inhibitor antibody to FIX developed. The median age at the time of anaphylaxis (or anaphylactoid reaction) was 16 months, and the median number of exposure days to FIX was 11. The FIX inhibitor was detected almost simultaneously with the first occurrence of anaphylaxis in 12 of 18 patients. Maximum inhibitor liters were 4.5-600 Bethesda units (BU), with a median titer of 48 BU. FIX gene analysis, performed in 17 of 18 patients, demonstrated complete deletion of the FIX gene in 10 and major derangements in seven. Immune tolerance induction (ITI) regimens have been attempted in 12 patients, with generally poor responses. Two of the 12 experienced nephrotic syndrome while on ITI. Recombinant FVIIa has been successfully used to treat bleeding episodes in 11 of these children. Conclusion: Physicians treating young children with hemophilia B should be aware of the potentially life- threatening complication of anaphylaxis. Children with complete gene deletions or major derangements of the 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 treatments in a medical facility equipped for handling such emergencies. Recombinant FVIIa, although not licensed for use in the United States, appears to be the most suitable treatment option for bleeding episodes in such patients.

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Contribution to journal
publication status
published
keywords
Anaphylaxis, Factor IX gene deletion, Factor IX inhibitor, Hemophilia B, Nephrotic syndrome, Recombinant factor VIIa, Paediatric
in
Journal of Pediatric Hematology/Oncology
volume
19
issue
1
pages
23 - 27
publisher
Lippincott Williams & Wilkins
external identifiers
  • Scopus:18844473466
ISSN
1077-4114
DOI
10.1097/00043426-199701000-00003
language
English
LU publication?
yes
id
433fce2b-3bc7-4af3-b549-cac52edb4cf3
date added to LUP
2016-11-25 14:48:55
date last changed
2016-11-30 17:05:19
@misc{433fce2b-3bc7-4af3-b549-cac52edb4cf3,
  abstract     = {<p>Purpose: We present clinical and laboratory data on 18 children from 12 hemophilia treatment centers in the United States, Canada, and Europe with the purpose of disseminating information regarding a recently recognized, potentially life-threatening complication of treatment in very young children with hemophilia B. Patients and Methods: Twelve hemophilia centers from the United States, Canada, and Europe provided clinical information and laboratory data concerning 18 children who had severe allergic reactions to infused factor (F) IX in close association with the development of an inhibitor to FIX. Laboratory testing for establishment of the diagnosis of hemophilia B and inhibitor to FIX was done locally at the centers treating these patients. FIX gene analysis was performed at one of six molecular genetics institutes. Results: All 18 children had severe hemophilia B, and in each an inhibitor antibody to FIX developed. The median age at the time of anaphylaxis (or anaphylactoid reaction) was 16 months, and the median number of exposure days to FIX was 11. The FIX inhibitor was detected almost simultaneously with the first occurrence of anaphylaxis in 12 of 18 patients. Maximum inhibitor liters were 4.5-600 Bethesda units (BU), with a median titer of 48 BU. FIX gene analysis, performed in 17 of 18 patients, demonstrated complete deletion of the FIX gene in 10 and major derangements in seven. Immune tolerance induction (ITI) regimens have been attempted in 12 patients, with generally poor responses. Two of the 12 experienced nephrotic syndrome while on ITI. Recombinant FVIIa has been successfully used to treat bleeding episodes in 11 of these children. Conclusion: Physicians treating young children with hemophilia B should be aware of the potentially life- threatening complication of anaphylaxis. Children with complete gene deletions or major derangements of the 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 treatments in a medical facility equipped for handling such emergencies. Recombinant FVIIa, although not licensed for use in the United States, appears to be the most suitable treatment option for bleeding episodes in such patients.</p>},
  author       = {Warrier, Indira and Ewenstein, Bruce M. and Koerper, Marion A. and Shapiro, Amy and Key, Nigel and DiMichele, Donna and Miller, Robert T. and Pasi, John and Rivard, Georges E. and Sommer, Steve S. and Katz, Jacob and Bergmann, Frauke and Ljung, Rolf and Petrini, Pia and Lusher, Jeanne M.},
  issn         = {1077-4114},
  keyword      = {Anaphylaxis,Factor IX gene deletion,Factor IX inhibitor,Hemophilia B,Nephrotic syndrome,Recombinant factor VIIa,Paediatric},
  language     = {eng},
  number       = {1},
  pages        = {23--27},
  publisher    = {ARRAY(0xb1def60)},
  series       = {Journal of Pediatric Hematology/Oncology},
  title        = {Factor IX inhibitors and anaphylaxis in hemophilia B},
  url          = {http://dx.doi.org/10.1097/00043426-199701000-00003},
  volume       = {19},
  year         = {1997},
}