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Published on: August 14, 2017
Validation Study of the Composite Score to Identify Von Willebrand Disease in Children
Lynn M Malec1, Charity G Moore, Carolyn M Bennett
1*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.
Insights
A new composite score shows promise for diagnosing type 1 von Willebrand disease (VWD) in children. A robust negative predictive value suggests VWD testing could be safely eliminated for many referred children.
Area of Science:
- Pediatric Hematology
- Hemostasis and Thrombosis
- Diagnostic Accuracy Studies
Background:
- Type 1 von Willebrand disease (VWD) diagnosis in children is challenging, often leading to delayed diagnosis post-surgery.
- A previously developed 4-variable composite score showed high sensitivity and specificity for VWD diagnosis.
- The score includes Tosetto bleeding score, family history, iron deficiency anemia history, and James early bleeding score.
Purpose of the Study:
- To prospectively validate a composite score of ≥ 2 for identifying children with type 1 VWD.
- To assess the diagnostic performance of the composite score in a pediatric population.
Main Methods:
- Prospective enrollment of children without a diagnosed bleeding disorder presenting for hematology evaluation.
- Calculation of sensitivity, specificity, positive predictive value, and negative predictive value for the composite score.
- Inclusion of 193 subjects from 12 participating centers.
Main Results:
- Forty-seven children were diagnosed with type 1 VWD.
- The composite score of ≥ 2 demonstrated a sensitivity of 63.6%–76.0% and specificity of 33.5%–35.1%.
- Negative predictive value ranged from 76.9% to 93.8%, with higher values at lower VWF:RCo levels.
Conclusions:
- The composite score exhibits a robust negative predictive value, particularly in cases with lower VWF:RCo.
- This suggests that VWD testing could potentially be omitted in approximately one-third of pediatric referrals.
- Further validation may refine the score's utility in clinical decision-making for VWD diagnosis in children.
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.
Procedure:
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.
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