Type 1 VWD classification revisited: novel insights from combined analysis of the LoVIC and WiN studies

Ferdows Atiq*, Robin Blok, Calvin B. van Kwawegen, Dearbhla Doherty, Michelle Lavin, Johanna G. van der Bom, Niamh M. O'Connell, Joke de Meris, Kevin Ryan, Saskia E.M. Schols, Mary Byrne, Floor C.J.I. Heubel-Moenen, Karin P.M. van Galen, Roger J.S. Preston, Marjon H. Cnossen, Karin Fijnvandraat, Ross I. Baker, Karina Meijer, Paula James, Jorge Di PaolaJeroen Eikenboom, Frank W.G. Leebeek, James S. O'Donnell

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF) levels <30 IU/dL be diagnosed type 1 VWD, whereas patients with significant bleeding and VWF levels from 30 to 50 IU/dL be diagnosed with low VWF. To elucidate the relationship between type 1 VWD and low VWF in the context of age-induced increases in VWF levels, we combined data sets from 2 national cohort studies: 162 patients with low VWF from the Low VWF in Ireland Cohort (LoVIC) and 403 patients with type 1 VWD from the Willebrand in The Netherlands (WiN) studies. In 47% of type 1 VWD participants, VWF levels remained <30 IU/dL despite increasing age. Conversely, VWF levels increased to the low VWF range (30-50 IU/dL) in 30% and normalized (>50 IU/dL) in 23% of type 1 VWD cases. Crucially, absolute VWF antigen (VWF:Ag) levels and increase of VWF:Ag per year overlapped between low VWF and normalized type 1 VWD participants. Moreover, multiple regression analysis demonstrated that VWF:Ag levels in low VWF and normalized type 1 VWD patients would not have been different had they been diagnosed at the same age (β = 0.00; 95% confidence interval, −0.03 to 0.04). Consistently, no difference was found in the prevalence of VWF sequence variants; factor VIII activity/VWF:Ag or VWF propeptide/VWF:Ag ratios; or desmopressin responses between low VWF and normalized type 1 VWD patients. In conclusion, our findings demonstrate that low VWF does not constitute a discrete clinical or pathological entity. Rather, it is part of an age-dependent type 1 VWD evolving phenotype. Collectively, these data have important implications for future VWD classification criteria.

Original languageEnglish
Pages (from-to)1414-1424
Number of pages11
JournalBlood
Volume143
Issue number14
Early online date24 Dec 2023
DOIs
Publication statusPublished - 4 Apr 2024

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© 2024 American Society of Hematology

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