The ratios between von Willebrand factor propeptide (VWFpp) or factor VIII activity (FVIII:C) and VWF antigen (VWF:Ag) reflect synthesis, secretion, and clearance of VWF. We aimed to define the pathophysiology of 658 patients with type 1, 2, or 3 von Willebrand disease (VWD) with VWF levels ≤30 U/dL from the Willebrand in The Netherlands (WiN) study using the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios. We evaluated the use of VWFpp in the classification and diagnosis of VWD. On the basis of the ratios, reduced VWF synthesis was observed in 18% of type 1 and only 2% of type 2 patients. A significant proportion of type 3 patients had detectable VWFpp (41%). These patients had a lower bleeding score than type 3 patients who had a complete absence of VWF:Ag and VWFpp (14.0 vs 19.5; P = .025). The majority of these patients had missense mutations with rapid VWF clearance, whereas type 3 patients with no VWFpp were homozygous for null alleles. In conclusion, VWFpp identified severe type 1 VWD with very low VWF levels in patients who had previously been classified as type 3 VWD. This study underlines the clinical significance of the VWFpp assay in the diagnosis and classification of VWD.,
Department of Pediatrics

Sanders, Y.V, Groeneveld, D, Meijer, K, Fijnvandraat, K, Cnossen, M.H, van der Bom, J.G, … Eikenboom, J.C.J. (2015). von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease. Blood, 125(19), 3006–3013. doi:10.1182/blood-2014-09-603241