Mapping Laboratory Phenotype-Genotype in Von Willebrand Disease: A Belgian National Survey

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