Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Blood, 2024-04, Vol.143 (14), p.1414-1424

Erscheinungsjahr

2024

Beschreibungen/Notizen

• 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.