title: von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease.
abstract: 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 and
  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.
authors: Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors: Yvonne V
authors: YV
authors: Sanders
authors: Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands;
authors: Dafna
authors: D
authors: Groeneveld
authors: University of Groningen, Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands;
authors: Karina
authors: K
authors: Meijer
authors: Pediatric Hematology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands;
authors: Karin
authors: K
authors: Fijnvandraat
authors: Pediatric Hematology, Erasmus University Medical Center-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands;
authors: Marjon H
authors: MH
authors: Cnossen
authors: Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Jon J. van Rood Center for Clinical Transfusion Medicine, Sanquin Research, Leiden, The Netherlands;
authors: Johanna G
authors: JG
authors: van der Bom
authors: Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors: M
authors: M
authors: Coppens
authors: Netherlands Hemophilia Society, Nijkerk, The Netherlands;
authors: Joke
authors: J
authors: de Meris
authors: Hematology, Radboud University Medical Center, Nijmegen, The Netherlands; and.
authors: Britta A P
authors: BA
authors: Laros-van Gorkom
authors: Van Creveldkliniek/Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Eveline P
authors: EP
authors: Mauser-Bunschoten
authors: Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors: Frank W G
authors: FW
authors: Leebeek
authors: Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands;
authors: Jeroen
authors: J
authors: Eikenboom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands; D010641:Phenotype; D011379:Prognosis; D011498:Protein Precursors / Q000235:genetics*; D055815:Young Adult; D014842:von Willebrand Diseases / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D011498:Protein Precursors; D014841:von Willebrand Factor