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Abstract Background

Von Willebrand Disease (VWD) is a common inherited bleeding disorder, arising from quantitative or qualitative defects in von Willebrand factor (VWF). Its wide phenotypic variability poses challenges for accurate diagnosis and subtype classification.

Objective

The B-Will Study is a comprehensive analysis of VWD within the Belgian population, focusing on phenotypic and genotypic characteristics.

Methods

Patients with suspected VWD were identified from historical records. Extensive laboratory phenotyping, including VWF multimer and genetic analysis, was performed in order to establish definitive VWD classification and subtyping.

Results

VWD was confirmed in 511 patients, with type 1 as the predominant subtype, followed by type 2 (especially, 2A/IIE and 2M-GPIbM). Laboratory phenotype and multimeric pattern were concordant in 75% of 323 cases. Genetic analysis revealed at least one causal variant in 92.7% of patients, uncovering 126 unique variants (58 novel variants). MLPA detected large gene deletions in cases lacking variants by direct sequencing, raising overall variant detection to 93.4%. Phenotype–genotype concordance reached 66% of the 247 fully characterized patients' subgroup.

Conclusion

The B-Will Study significantly enhances understanding of VWD in Belgium, demonstrating that integrated phenotypic and genotypic evaluation improves diagnostic accuracy and subtype classification. The established VWD biobank provides a foundation for longitudinal studies, advanced genetic testing, and international collaboration to optimize VWD management.

Keywords Von Willebrand disease - Von Willebrand factor - phenotype–genotype correlation - genetic analysis - national survey Contributors' Statement

A.G. and I.V. were responsible for the study initiation, study design, data collection, performing laboratory analysis, interpretation of results, and statistical analysis. S.D.B., C.O., P.C., C.H., N.F. M.A., I.B., and A.G. were responsible for the sample collection. A.G. was responsible for the review and approval of the final manuscript.

Publication History

Received: 31 July 2025

Accepted after revision: 06 March 2026

Article published online:
20 March 2026

© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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