title: Validation Study of the Composite Score to Identify Von Willebrand Disease in Children.
abstract: BACKGROUND
  The diagnosis of type 1 von Willebrand disease (VWD) presents a diagnostic challenge in children. In fact, 25% or more of children with VWD may be diagnosed only after they experience postoperative bleeding. We previously described a 4-variable composite score that has 92.5% sensitivity and 95% specificity for diagnosing VWD in children with known VWD when 2 of 4 criteria are positive: (1) Tosetto bleeding score ≥ 1; (2) family history of VWD; (3) personal history of iron deficiency anemia; and/or (4) positive James early bleeding score. The purpose of this study was to prospectively validate a composite score of ≥ 2 for identifying children with VWD.
  
  
  METHODS
  Children without a previously diagnosed bleeding disorder presenting for hematology evaluation were enrolled. Sensitivity, specificity, positive, and negative predictive value of the composite score was determined.
  
  
  RESULTS
  A total of 193 subjects were enrolled from 12 participating centers were included in the analysis. Forty-seven children had type 1 VWD, including 11 with von Willebrand Ristocetin Cofactor (VWF):RCo < 30 IU/dL, 14 subjects with a VWF:RCo 30 to 39 IU/dL, and 22 with a VWF:RCo 40 to 49 IU/dL. Including all 4 variables, a composite score of ≥ 2 had a sensitivity of 63.6% to 76.0%, specificity of 33.5% to 35.1%, negative predictive value of 76.9% to 93.8%, and positive predictive value of 5.5% to 25%.
  
  
  CONCLUSIONS
  The negative predictive value of the composite score was robust, especially at lower VWF:RCo suggesting that VWD testing could be eliminated in nearly a third of children referred for VWD testing.
authors.affiliation: *Children's Hospital of Pittsburgh, Hemophilia Center of Western PA ††Children's Hospital of Pittsburgh, University of Pittsburgh †Center for Healthcare Research Data Center, University of Pittsburgh School of Medicine ∥∥University of Pittsburgh, Hemophilia Center of Western PA, Pittsburgh ¶The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA ‡Children's Healthcare of Atlanta at Scottish Rite, Emory University School of Medicine, Atlanta, GA §Texas Children's Hospital, Baylor College of Medicine §§University of Texas, Houston, TX ∥Nationwide Children's Hospital, The Ohio State University, Columbus, OH #Pediatrics & Human Development, Michigan State University, East Lansing, MI **Indiana Hemophilia & Thrombosis Center, Indianapolis, IN ‡‡Rochester General Hospital, Rochester, NY.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Malec
authors.forename: Charity G
authors.initials: CG
authors.lastname: Moore
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Bennett
authors.forename: Donald L
authors.initials: DL
authors.lastname: Yee
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Kerlin
authors.forename: Char M
authors.initials: CM
authors.lastname: Witmer
authors.forename: Roshni
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Sweta
authors.initials: S
authors.lastname: Gupta
authors.forename: Sriya
authors.initials: S
authors.lastname: Gunawardena
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kouides
authors.forename: Deborah
authors.initials: D
authors.lastname: Brown
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Ragni
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006405:Hematology / Q000379:methods*; D006801:Humans; D008297:Male; D012680:Sensitivity and Specificity; D056725:von Willebrand Disease, Type 1 / Q000175:diagnosis*