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 patients with 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haematology/Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: ter Avest
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.forename: M E
authors.initials: ME
authors.lastname: Mancuso
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
authors.forename: V J
authors.initials: VJ
authors.lastname: Yuste
authors.forename: H M
authors.initials: HM
authors.lastname: van den Berg
authors.forename: J G
authors.initials: JG
authors.lastname: van der Bom
mesh_terms: D000465:Algorithms; D000906:Antibodies / Q000097:blood*; D000917:Antibody Formation; D005169:Factor VIII / Q000276:immunology; D006467:Hemophilia A / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000906:Antibodies; D005169:Factor VIII