Clinical phenotype and pathophysiological mechanisms underlying qualitative Low VWF

• DOI: 10.1182/blood.2024028035
• Publication Date: 2025-04-25T19:34:13Z
• Authors: Ferdows Atiq; Robin Blok; Calvin van Kwawegen; Anne-Marije Hulshof; Dearbhla Doherty; Michelle Lavin; Johanna G van der...; Niamh M O'Connell; Joke de Meris; Kevin Ryan; Saskia E.M. Schols; Waander L. van He...; Mairead M Doyle; Mary B Byrne; Floor C.J.I. Heub...; Karin P.M. van Galen; Roger J.S. Preston; Marjon H. Cnossen; Karin Fijnvandraat; Ross Ian Baker; Karina Meijer; Paula D. James; Jorge Di Paola; Jeroen C.J. Eiken...; Frank W.G. Leebeek; James S. O'Donnell
• Keywords: von Willebrand Disease

Previous reports have highlighted that some low VWF patients with significant bleeding were diagnosed based upon an isolated but persistent reduction in plasma activity levels the 30-50 IU/dL range. These had VWF:Ag > 50 and thus 'qualitative' rather than 'quantitative' VWF. Although clinical importance of functional defects type 2 VWD is well recognized, translational implications mild qualitative (low VWF-QL) not been defined. To address this clinically important question, we combined datasets from Ireland cohort Erasmus MC studies. Overall, observed VWF-QL was common accounted for approximately 50% our cohort. Importantly, findings demonstrate many these IU/dl range phenotypes, even though their within normal In addition, further show a distinct clinic-pathological entity compared to VWD. Finally, studies highlight predominantly due abnormalities biosynthesis endothelial cells are occurring largely independent identifiable pathological sequence variants. Cumulatively, novel observations diagnosis management defects.