title: Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD).
abstract: The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propeptide (VWFpp) can be used to identify patients with reduced VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the 7 individuals. Thus, a substantially increased ratio of steady-state VWFpp/VWF:Ag predicted a reduced VWF half-life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a subpopulation of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, USA. shaberic@mcw.edu
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Haberichter
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.forename: Ulrich
authors.initials: U
authors.lastname: Budde
authors.forename: Ian
authors.initials: I
authors.lastname: Peake
authors.forename: Anne
authors.initials: A
authors.lastname: Goodeve
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: Augusto B
authors.initials: AB
authors.lastname: Federici
authors.forename: Javier
authors.initials: J
authors.lastname: Batlle
authors.forename: Dominique
authors.initials: D
authors.lastname: Meyer
authors.forename: Claudine
authors.initials: C
authors.lastname: Mazurier
authors.forename: Jenny
authors.initials: J
authors.lastname: Goudemand
authors.forename: Jeroen
authors.initials: J
authors.lastname: Eikenboom
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Jorgen
authors.initials: J
authors.lastname: Ingerslev
authors.forename: Zdena
authors.initials: Z
authors.lastname: Vorlova
authors.forename: David
authors.initials: D
authors.lastname: Habart
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Lethagen
authors.forename: John
authors.initials: J
authors.lastname: Pasi
authors.forename: Frank G H
authors.initials: FG
authors.lastname: Hill
authors.forename: Robert R
authors.initials: RR
authors.lastname: Montgomery
mesh_terms: D015415:Biomarkers / Q000097:blood; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D005060:Europe; D006207:Half-Life; D006801:Humans; D009154:Mutation; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome; D014842:von Willebrand Diseases / Q000175:diagnosis* / Q000401:mortality*; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin