Rapid discrimination of the phenotypic variants of von Willebrand disease. Blood 2016 May 19;127(20):2472-80
Date
02/27/2016Pubmed ID
26917779Pubmed Central ID
PMC4874227DOI
10.1182/blood-2015-11-664680Scopus ID
2-s2.0-84974623429 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
Author List
Roberts JC, Morateck PA, Christopherson PA, Yan K, Hoffmann RG, Gill JC, Montgomery RR, Zimmerman Program InvestigatorsAuthor
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Data AccuracyDiscriminant Analysis
Enzyme-Linked Immunosorbent Assay
Genetic Testing
Genotype
Hemophilia A
Humans
Phenotype
Probability
ROC Curve
Reproducibility of Results
Sensitivity and Specificity
Time Factors
von Willebrand Diseases
von Willebrand Factor