Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A

E. A. Chalmers, S. A. Brown, D. Keeling, R. Liesner, M. Richards, D. Stirling, A. Thomas, V. Vidler, M. D. Williams, D. Young, Paediatric Working Party of UKHCDO

Research output: Contribution to journalArticle

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Abstract

Recent reports have suggested that the incidence of inhibitors in haemophilia is the highest in those first exposed to factor VIII under 6 months of age. In this study, we investigated inhibitor development in children first exposed to FVIII as neonates and also examined the effect of other genetic and environmental variables. Three hundred and forty-eight children with severe haemophilia A were investigated. Inhibitors developed in 68 of 348 (20%), with 34 of 348 (10%) high titre inhibitors. The incidence in relation to initial FVIII exposure was: <1 month nine of 35 (26%), 1-6 months 13 of 51 (25%), 6-12 months 27 of 130 (21%), 12-18 months 13 of 66 (20%) and >18 months six of 66 (9%). While we observed a significant difference in inhibitor development and age at first exposure across all age groups (P = 0.018), no significant difference was observed in children treated at different time points during the first year of life (P = 0.44). Similar results were obtained for high titre inhibitors. There was also no difference in the incidence of inhibitors in relation to initial FVIII exposure in a subgroup of 144 children with the intron 22 mutation. Inhibitors developed more frequently in those initially treated with recombinant when compared with plasma-derived FVIII (P = 0.006) and in those with a major molecular defect (P = 0.009). In this study, exposure to FVIII during the neonatal period was not associated with a higher incidence of inhibitors than those treated later during the first year of life. Initial treatment with recombinant FVIII and the presence of a major molecular defect were the most important variables affecting inhibitor development.

LanguageEnglish
Pages149-55
Number of pages7
JournalHaemophilia
Volume13
Issue number2
Early online date23 Jan 2007
DOIs
Publication statusPublished - 1 Mar 2007

Fingerprint

Factor VIII
Hemophilia A
Child Development
Incidence
Introns
Age Groups
Newborn Infant
Mutation
Therapeutics

Keywords

  • adolescent
  • age of onset
  • blood coagulation factor inhibitors
  • child
  • preschool child
  • factor VIII
  • hemophilia A
  • humans
  • infant
  • newborn infant
  • pedigree
  • risk factors

Cite this

Chalmers, E. A., Brown, S. A., Keeling, D., Liesner, R., Richards, M., Stirling, D., ... Paediatric Working Party of UKHCDO (2007). Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. Haemophilia, 13(2), 149-55. https://doi.org/10.1111/j.1365-2516.2006.01418.x
Chalmers, E. A. ; Brown, S. A. ; Keeling, D. ; Liesner, R. ; Richards, M. ; Stirling, D. ; Thomas, A. ; Vidler, V. ; Williams, M. D. ; Young, D. ; Paediatric Working Party of UKHCDO. / Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. In: Haemophilia. 2007 ; Vol. 13, No. 2. pp. 149-55.
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Chalmers, EA, Brown, SA, Keeling, D, Liesner, R, Richards, M, Stirling, D, Thomas, A, Vidler, V, Williams, MD, Young, D & Paediatric Working Party of UKHCDO 2007, 'Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A' Haemophilia, vol. 13, no. 2, pp. 149-55. https://doi.org/10.1111/j.1365-2516.2006.01418.x

Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. / Chalmers, E. A.; Brown, S. A.; Keeling, D.; Liesner, R.; Richards, M.; Stirling, D.; Thomas, A.; Vidler, V.; Williams, M. D.; Young, D.; Paediatric Working Party of UKHCDO.

In: Haemophilia, Vol. 13, No. 2, 01.03.2007, p. 149-55.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A

AU - Chalmers, E. A.

AU - Brown, S. A.

AU - Keeling, D.

AU - Liesner, R.

AU - Richards, M.

AU - Stirling, D.

AU - Thomas, A.

AU - Vidler, V.

AU - Williams, M. D.

AU - Young, D.

AU - Paediatric Working Party of UKHCDO

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Recent reports have suggested that the incidence of inhibitors in haemophilia is the highest in those first exposed to factor VIII under 6 months of age. In this study, we investigated inhibitor development in children first exposed to FVIII as neonates and also examined the effect of other genetic and environmental variables. Three hundred and forty-eight children with severe haemophilia A were investigated. Inhibitors developed in 68 of 348 (20%), with 34 of 348 (10%) high titre inhibitors. The incidence in relation to initial FVIII exposure was: <1 month nine of 35 (26%), 1-6 months 13 of 51 (25%), 6-12 months 27 of 130 (21%), 12-18 months 13 of 66 (20%) and >18 months six of 66 (9%). While we observed a significant difference in inhibitor development and age at first exposure across all age groups (P = 0.018), no significant difference was observed in children treated at different time points during the first year of life (P = 0.44). Similar results were obtained for high titre inhibitors. There was also no difference in the incidence of inhibitors in relation to initial FVIII exposure in a subgroup of 144 children with the intron 22 mutation. Inhibitors developed more frequently in those initially treated with recombinant when compared with plasma-derived FVIII (P = 0.006) and in those with a major molecular defect (P = 0.009). In this study, exposure to FVIII during the neonatal period was not associated with a higher incidence of inhibitors than those treated later during the first year of life. Initial treatment with recombinant FVIII and the presence of a major molecular defect were the most important variables affecting inhibitor development.

AB - Recent reports have suggested that the incidence of inhibitors in haemophilia is the highest in those first exposed to factor VIII under 6 months of age. In this study, we investigated inhibitor development in children first exposed to FVIII as neonates and also examined the effect of other genetic and environmental variables. Three hundred and forty-eight children with severe haemophilia A were investigated. Inhibitors developed in 68 of 348 (20%), with 34 of 348 (10%) high titre inhibitors. The incidence in relation to initial FVIII exposure was: <1 month nine of 35 (26%), 1-6 months 13 of 51 (25%), 6-12 months 27 of 130 (21%), 12-18 months 13 of 66 (20%) and >18 months six of 66 (9%). While we observed a significant difference in inhibitor development and age at first exposure across all age groups (P = 0.018), no significant difference was observed in children treated at different time points during the first year of life (P = 0.44). Similar results were obtained for high titre inhibitors. There was also no difference in the incidence of inhibitors in relation to initial FVIII exposure in a subgroup of 144 children with the intron 22 mutation. Inhibitors developed more frequently in those initially treated with recombinant when compared with plasma-derived FVIII (P = 0.006) and in those with a major molecular defect (P = 0.009). In this study, exposure to FVIII during the neonatal period was not associated with a higher incidence of inhibitors than those treated later during the first year of life. Initial treatment with recombinant FVIII and the presence of a major molecular defect were the most important variables affecting inhibitor development.

KW - adolescent

KW - age of onset

KW - blood coagulation factor inhibitors

KW - child

KW - preschool child

KW - factor VIII

KW - hemophilia A

KW - humans

KW - infant

KW - newborn infant

KW - pedigree

KW - risk factors

U2 - 10.1111/j.1365-2516.2006.01418.x

DO - 10.1111/j.1365-2516.2006.01418.x

M3 - Article

VL - 13

SP - 149

EP - 155

JO - Haemophilia

T2 - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - 2

ER -