von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease
Blood , Volume 125 - Issue 19 p. 3006- 3013
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.
|Organisation||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