The Relationship between Low Von Willebrand Factor, Type 1 Von Willebrand Disease and Ageing - Novel Insights from the Lovic and Win Cohort Studies

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.509-509
• Main Authors: Atiq, Ferdows, Blok, Robin, Van Kwawegen, Calvin, Doherty, Dearbhla, Lavin, Michelle, Van Der Bom, Johanna G., O'Connell, Niamh, De Meris, Joke, Ryan, Kevin, Schols, Saskia, Byrne, Mary, Moenen, Floor, Van Galen, Karin PM, Preston, Roger J.S, Fijnvandraat, Karin, Baker, Ross, Meijer, Karina, James, Paula, Di Paola, Jorge, Eikenboom, Jeroen, Leebeek, Frank W.G., O'Donnell, James S.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-181603

Introduction For many years, there has been debate about how to optimally diagnose type 1 VWD. Initial guidelines proposed that only individuals with plasma VWF levels < 30 IU/dL should be diagnosed with ‘type 1 VWD’. This was revised in recent ASH/ISTH/WFH/NHF panel which recommended that patients with a significant bleeding history and plasma VWF of 30-50 IU/dL should also be diagnosed with type 1 VWD, as opposed to the discrete ‘Low VWF’ entity proposed in previous guidelines. In this study, we investigated whether Low VWF is a discrete clinical entity, or whether it is instead part of an age-dependent type 1 VWD evolving phenotype. Methods We utilized datasets from two renowned national cohort studies - the Low VWF in Ireland Cohort (LoVIC) and Willebrand in the Netherlands (WiN) studies. In the LoVIC study, patients had a personal bleeding history and historically lowest VWF levels in the 30-50 IU/dL range. In the WiN study, patients had either a personal bleeding history or positive family history, combined with historically lowest VWF levels ≤ 30 IU/dL. Based upon levels at study inclusion versus original diagnosis, WiN patients were categorized into three groups - (i) patients with persistent VWF levels 50 IU/dL. The FVIII:C/VWF:Ag ratio was used to assess the synthesis/secretion of VWF and the VWFpp/VWF:Ag ratio was used to assess the clearance of VWF. Results In total, 565 patients were included (403 WiN patients with type 1 VWD and 162 LoVIC patients with Low VWF). Mean age at diagnosis was significantly increased in the LoVIC cohort compared to the three WiN subgroups (32.5 years versus 23.3 years, 26.5 years and 25 years respectively; p 50 IU/dL. Similarly, 39% (n=63) of