Rapid discrimination of the phenotypic variants of von Willebrand disease

Blood. 2016 May 19;127(20):2472-80. doi: 10.1182/blood-2015-11-664680. Epub 2016 Feb 25.

Abstract

Approximately 20% to 25% of patients with von Willebrand disease (VWD) have a qualitative defect of the von Willebrand factor (VWF) protein activities. Variant VWD typically is classified as type 1C, 2A, 2B, 2M, or 2N depending on the VWF activity defect. Traditionally, diagnosis has relied on multiple clinical laboratory assays to assign VWD phenotype. We developed an enzyme-linked immunosorbent assay (ELISA) to measure the various activities of VWF on a single plate and evaluated 160 patient samples enrolled in the Zimmerman Program for the Molecular and Clinical Biology of von Willebrand Disease with type 2 VWD. Using linear discriminate analysis (LDA), this assay was able to identify type 1C, 2A, 2B, 2M, or 2N VWD with an overall accuracy of 92.5% in the patient study cohort. LDA jackknife analysis, a statistical resampling technique, identified variant VWD with an overall accuracy of 88.1%, which predicts the assay's performance in the general population. In addition, this assay demonstrated correlation with traditional clinical laboratory VWF assays. The VWF multiplex activity assay may be useful as a same-day screening assay when considering the diagnosis of variant VWD in an individual patient.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Data Accuracy
  • Discriminant Analysis
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Genetic Testing
  • Genotype
  • Hemophilia A / blood
  • Humans
  • Phenotype
  • Probability
  • ROC Curve
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Time Factors
  • von Willebrand Diseases / blood
  • von Willebrand Diseases / classification*
  • von Willebrand Diseases / diagnosis
  • von Willebrand Diseases / genetics
  • von Willebrand Factor / analysis*
  • von Willebrand Factor / genetics

Substances

  • Von Willebrand antigen
  • von Willebrand Factor