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

There is significant ongoing debate regarding type 1 VWD defintion. Previous guidelines recommended patients with VWF levels 50 IU/dL) in 23% of WiN cases. Crucially, absolute VWF:Ag levels and increase of VWF:Ag per year overlapped between Low VWF and normalized-WiN subjects. Moreover, multiple regression analysis demonstrated that VWF:Ag levels in LoVIC cohort and WiN-normalized patients would not have been different had they been diagnosed at the same age (β=0.00, 95%CI -0.03-0.04). Consistently, no difference was found in the prevalence of VWF sequence variants; FVIII:C/VWF:Ag or VWFpp/VWF:Ag ratios; or desmopressin responses between LoVIC and WiN-normalized 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.</p