Risk stratification for inhibitor development at first treatment for severe hemophilia A: A tool for clinical practice

P. C. ter Avest, K. Fischer, M. E. Mancuso, E. Santagostino, V. J. Yuste, H. M. van den Berg, Johanna G. van der Bom

Research output: Contribution to journalArticle

Abstract

Background: Replacement therapy in severe hemophilia A patients is complicated by formation of inhibitory antibodies against factor VIII (inhibitors) in around 25% of children. Management of bleeds and eradicating inhibitors is complicated, costly and not always successful. Objective: To develop a simple score that stratifies untreated patientswith severe hemophilia according to their risk of developing inhibitory antibodies. Methods: The study population consisted of 332 children, with severe hemophilia A, selected from a retrospective multicentre cohort (the CANAL study). The score was based on risk factors available at the first treatment episode. The score was validated in an external population. Results: A total of 87 patients (25%) developed inhibitory antibodies. The selected risk score comprised positive family history (two points), high risk factor VIII gene mutations (two points), and intensive treatment at initial treatment (three points). Inhibitor incidence was 6% (six of 95) in patients without risk factor, 23% (38 of 170) in those with two points, and 57% (38 of 67) in patients with three points or more. The discriminative ability of the score was good (area under the receiver operating curve 0.74). The score performed equally well in the external validation population. Conclusion: These findings suggest that the development of inhibitory antibodies in untreated patients with severe hemophilia A can validly be predicted with the presented risk stratification score.

Original languageEnglish
Pages (from-to)2048-2054
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number12
DOIs
Publication statusPublished - 2008

Fingerprint

Hemophilia A
Factor VIII
Antibodies
Population
Therapeutics
Aptitude
Point Mutation
Antibody Formation
Cohort Studies
Incidence
Genes

Keywords

  • Antibody
  • Hemophilia A
  • Intensive treatment
  • Risk score

ASJC Scopus subject areas

  • Hematology

Cite this

Risk stratification for inhibitor development at first treatment for severe hemophilia A : A tool for clinical practice. / ter Avest, P. C.; Fischer, K.; Mancuso, M. E.; Santagostino, E.; Yuste, V. J.; van den Berg, H. M.; van der Bom, Johanna G.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 12, 2008, p. 2048-2054.

Research output: Contribution to journalArticle

ter Avest, P. C. ; Fischer, K. ; Mancuso, M. E. ; Santagostino, E. ; Yuste, V. J. ; van den Berg, H. M. ; van der Bom, Johanna G. / Risk stratification for inhibitor development at first treatment for severe hemophilia A : A tool for clinical practice. In: Journal of Thrombosis and Haemostasis. 2008 ; Vol. 6, No. 12. pp. 2048-2054.
@article{5df7a1f4c41d4f198160e37d4c787287,
title = "Risk stratification for inhibitor development at first treatment for severe hemophilia A: A tool for clinical practice",
abstract = "Background: Replacement therapy in severe hemophilia A patients is complicated by formation of inhibitory antibodies against factor VIII (inhibitors) in around 25{\%} of children. Management of bleeds and eradicating inhibitors is complicated, costly and not always successful. Objective: To develop a simple score that stratifies untreated patientswith severe hemophilia according to their risk of developing inhibitory antibodies. Methods: The study population consisted of 332 children, with severe hemophilia A, selected from a retrospective multicentre cohort (the CANAL study). The score was based on risk factors available at the first treatment episode. The score was validated in an external population. Results: A total of 87 patients (25{\%}) developed inhibitory antibodies. The selected risk score comprised positive family history (two points), high risk factor VIII gene mutations (two points), and intensive treatment at initial treatment (three points). Inhibitor incidence was 6{\%} (six of 95) in patients without risk factor, 23{\%} (38 of 170) in those with two points, and 57{\%} (38 of 67) in patients with three points or more. The discriminative ability of the score was good (area under the receiver operating curve 0.74). The score performed equally well in the external validation population. Conclusion: These findings suggest that the development of inhibitory antibodies in untreated patients with severe hemophilia A can validly be predicted with the presented risk stratification score.",
keywords = "Antibody, Hemophilia A, Intensive treatment, Risk score",
author = "{ter Avest}, {P. C.} and K. Fischer and Mancuso, {M. E.} and E. Santagostino and Yuste, {V. J.} and {van den Berg}, {H. M.} and {van der Bom}, {Johanna G.}",
year = "2008",
doi = "10.1111/j.1538-7836.2008.03187.x",
language = "English",
volume = "6",
pages = "2048--2054",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "12",

}

TY - JOUR

T1 - Risk stratification for inhibitor development at first treatment for severe hemophilia A

T2 - A tool for clinical practice

AU - ter Avest, P. C.

AU - Fischer, K.

AU - Mancuso, M. E.

AU - Santagostino, E.

AU - Yuste, V. J.

AU - van den Berg, H. M.

AU - van der Bom, Johanna G.

PY - 2008

Y1 - 2008

N2 - Background: Replacement therapy in severe hemophilia A patients is complicated by formation of inhibitory antibodies against factor VIII (inhibitors) in around 25% of children. Management of bleeds and eradicating inhibitors is complicated, costly and not always successful. Objective: To develop a simple score that stratifies untreated patientswith severe hemophilia according to their risk of developing inhibitory antibodies. Methods: The study population consisted of 332 children, with severe hemophilia A, selected from a retrospective multicentre cohort (the CANAL study). The score was based on risk factors available at the first treatment episode. The score was validated in an external population. Results: A total of 87 patients (25%) developed inhibitory antibodies. The selected risk score comprised positive family history (two points), high risk factor VIII gene mutations (two points), and intensive treatment at initial treatment (three points). Inhibitor incidence was 6% (six of 95) in patients without risk factor, 23% (38 of 170) in those with two points, and 57% (38 of 67) in patients with three points or more. The discriminative ability of the score was good (area under the receiver operating curve 0.74). The score performed equally well in the external validation population. Conclusion: These findings suggest that the development of inhibitory antibodies in untreated patients with severe hemophilia A can validly be predicted with the presented risk stratification score.

AB - Background: Replacement therapy in severe hemophilia A patients is complicated by formation of inhibitory antibodies against factor VIII (inhibitors) in around 25% of children. Management of bleeds and eradicating inhibitors is complicated, costly and not always successful. Objective: To develop a simple score that stratifies untreated patientswith severe hemophilia according to their risk of developing inhibitory antibodies. Methods: The study population consisted of 332 children, with severe hemophilia A, selected from a retrospective multicentre cohort (the CANAL study). The score was based on risk factors available at the first treatment episode. The score was validated in an external population. Results: A total of 87 patients (25%) developed inhibitory antibodies. The selected risk score comprised positive family history (two points), high risk factor VIII gene mutations (two points), and intensive treatment at initial treatment (three points). Inhibitor incidence was 6% (six of 95) in patients without risk factor, 23% (38 of 170) in those with two points, and 57% (38 of 67) in patients with three points or more. The discriminative ability of the score was good (area under the receiver operating curve 0.74). The score performed equally well in the external validation population. Conclusion: These findings suggest that the development of inhibitory antibodies in untreated patients with severe hemophilia A can validly be predicted with the presented risk stratification score.

KW - Antibody

KW - Hemophilia A

KW - Intensive treatment

KW - Risk score

UR - http://www.scopus.com/inward/record.url?scp=56749175272&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=56749175272&partnerID=8YFLogxK

U2 - 10.1111/j.1538-7836.2008.03187.x

DO - 10.1111/j.1538-7836.2008.03187.x

M3 - Article

C2 - 18983511

AN - SCOPUS:56749175272

VL - 6

SP - 2048

EP - 2054

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 12

ER -