von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease
Yvonne V Sanders, Dafna Groeneveld, Karina Meijer, Karin Fijnvandraat, Marjon H Cnossen, Johanna G van der Bom, M Coppens, Joke de Meris, Britta A P Laros-van Gorkom, Eveline P Mauser-Bunschoten, Frank W G Leebeek, Jeroen Eikenboom, WiN study group, K Fijnvandraat, M Coppens, A Kors, S Zweegman, J de Meris, G J Goverde, M H Jonkers, N Dors, M R Nijziel, K Meijer, R Y J Tamminga, P W van der Linden, P F Ypma, J G van der Bom, J Eikenboom, F J W Smiers, B Granzen, K Hamulyák, P Brons, B A P Laros-van Gorkom, M H Cnossen, F W G Leebeek, Y V Sanders, E P Mauser-Bunschoten, Yvonne V Sanders, Dafna Groeneveld, Karina Meijer, Karin Fijnvandraat, Marjon H Cnossen, Johanna G van der Bom, M Coppens, Joke de Meris, Britta A P Laros-van Gorkom, Eveline P Mauser-Bunschoten, Frank W G Leebeek, Jeroen Eikenboom, WiN study group, K Fijnvandraat, M Coppens, A Kors, S Zweegman, J de Meris, G J Goverde, M H Jonkers, N Dors, M R Nijziel, K Meijer, R Y J Tamminga, P W van der Linden, P F Ypma, J G van der Bom, J Eikenboom, F J W Smiers, B Granzen, K Hamulyák, P Brons, B A P Laros-van Gorkom, M H Cnossen, F W G Leebeek, Y V Sanders, E P Mauser-Bunschoten
Abstract
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.
© 2015 by The American Society of Hematology.
Source: PubMed