TY - JOUR
T1 - von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease
AU - Sanders, Yvonne V.
AU - Groeneveld, Dafna
AU - Meijer, Karina
AU - Fijnvandraat, Karin
AU - Cnossen, Marjon H.
AU - van der Bom, Johanna G.
AU - Coppens, M.
AU - de Meris, Joke
AU - Laros-van Gorkom, Britta A. P.
AU - Mauser-Bunschoten, Eveline P.
AU - Leebeek, Frank W. G.
AU - Eikenboom, Jeroen
PY - 2015/5/7
Y1 - 2015/5/7
N2 - The ratios between von Willebrand factor propeptide (VWFpp) or factor VIII activity (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 andC/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.
AB - The ratios between von Willebrand factor propeptide (VWFpp) or factor VIII activity (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 andC/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.
U2 - 10.1182/blood-2014-09-603241
DO - 10.1182/blood-2014-09-603241
M3 - Article
C2 - 25673639
SN - 0006-4971
VL - 125
SP - 3006
EP - 3013
JO - Blood
JF - Blood
IS - 19
ER -