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Journal article
Clinical phenotype and pathophysiological mechanisms underlying qualitative low VWF
Blood
2025
PMID: 40279514
Abstract
[Display omitted]
Previous reports have highlighted that some patients with low levels of von Willebrand factor (VWF) and significant bleeding were diagnosed based on an isolated but persistent reduction in plasma VWF activity levels in the 30 to 50 IU/dL range. These patients had plasma VWF antigen (VWF:Ag) levels >50 IU/dL and thus had qualitative low VWF (low VWF–QL) rather than quantitative low VWF. Although the clinical importance of functional VWF defects in type 2 von Willebrand disease (VWD) is well recognized, the translational implications of mild functional defects in patients with low VWF–QL have not been defined. To address this clinically important question, we combined low VWF data sets from the low VWF in Ireland cohort and the low VWF in Erasmus MC studies. Overall, we observed that low VWF–QL was common and accounted for ∼50% of our combined low VWF cohort. Importantly, our findings demonstrated that many of these patients with mild isolated functional VWF defects in the 30 to 50 IU/dL range had significant bleeding phenotypes, although their plasma VWF:Ag levels were within the normal range. In addition, we further showed that low VWF–QL is a distinct clinic-pathological entity that is different from type 2 VWD. Finally, our studies highlighted that low VWF–QL is predominantly caused by abnormalities in VWF biosynthesis within endothelial cells that are occurring largely independent of identifiable pathological VWF sequence variants. Cumulatively, these novel observations have important clinical implications for the diagnosis and management of patients with mild functional VWF defects.
Details
- Title
- Clinical phenotype and pathophysiological mechanisms underlying qualitative low VWF
- Authors/Creators
- Ferdows Atiq - Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, IrelandRobin Blok - Erasmus MCCalvin B. van Kwawegen - Erasmus MCAnne-Marije Hulshof - Royal College of Surgeons in IrelandDearbhla Doherty - Royal College of Surgeons in IrelandMichelle Lavin - Royal College of Surgeons in IrelandJohanna G. van der Bom - Leiden University Medical CenterNiamh M. O’Connell - St. James's HospitalJoke de Meris - Nederlandse Vereniging voor KindergeneeskundeKevin Ryan - St. James's HospitalSaskia E. M. Schols - Radboud University NijmegenWaander L. van Heerde - Radboud University NijmegenMairead Doyle - St. James's HospitalMary Byrne - St. James's HospitalFloor C. J. I. Heubel-Moenen - Maastricht UniversityKarin P. M. van Galen - University Medical Center UtrechtRoger J. S. Preston - Royal College of Surgeons in IrelandMarjon H. Cnossen - Erasmus MC - Sophia Children’s HospitalKarin Fijnvandraat - Amsterdam University Medical CentersKarina Meijer - University Medical Center GroningenRoss I. Baker - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsPaula James - Queen's UniversityJorge Di Paola - Washington University in St. LouisJeroen Eikenboom - Leiden University Medical CenterFrank W. G. Leebeek - Erasmus MCJames S. O’Donnell - Royal College of Surgeons in Ireland
- Publication Details
- Blood
- Publisher
- Elsevier Inc.
- Identifiers
- 991005779518207891
- Copyright
- © 2025 American Society of Hematology
- Murdoch Affiliation
- Murdoch University; Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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