title: Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD).
abstract: BACKGROUND
  Type 1 von Willebrand disease (VWD) is a congenital bleeding disorder characterized by a partial quantitative deficiency of plasma von Willebrand factor (VWF) in the absence of structural and/or functional VWF defects. Accurate assessment of the quantity and quality of plasma VWF is difficult but is a prerequisite for correct classification.
  
  
  OBJECTIVE
  To evaluate the proportion of misclassification of patients historically diagnosed with type 1 VWD using detailed analysis of the VWF multimer structure.
  
  
  METHODS
  Previously diagnosed type 1 VWD families and healthy controls were recruited by 12 expert centers in nine European countries. Phenotypic characterization comprised plasma VWF parameters and multimer analysis using low- and intermediate-resolution gels combined with an optimized visualization system. VWF genotyping was performed in all index cases (ICs).
  
  
  RESULTS
  Abnormal multimers were present in 57 out of 150 ICs; however, only 29 out of these 57 (51%) had VWF ristocetin cofactor to antigen ratio below 0.7. In most cases multimer abnormalities were subtle, and only two cases had a significant loss of the largest multimers.
  
  
  CONCLUSIONS
  Of the cases previously diagnosed as type 1 VWD, 38% showed abnormal multimers. Depending on the classification criteria used, 22 out of these 57 cases (15% of the total cohort) may be reclassified as type 2, emphasizing the requirement for multimer analysis compared with a mere ratio of VWF functional parameters and VWF:Ag. This is further supported by the finding that even slightly aberrant multimers are highly predictive for the presence of VWF mutations.
authors.affiliation: Coagulation Laboratory, Hamburg, Germany. ulrich.budde@aesculabor-hamburg.de
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: R
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: J
authors.initials: J
authors.lastname: Eikenboom
authors.forename: A
authors.initials: A
authors.lastname: Goodeve
authors.forename: K
authors.initials: K
authors.lastname: Will
authors.forename: E
authors.initials: E
authors.lastname: Drewke
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: A B
authors.initials: AB
authors.lastname: Federici
authors.forename: J
authors.initials: J
authors.lastname: Batlle
authors.forename: A
authors.initials: A
authors.lastname: Pérez
authors.forename: D
authors.initials: D
authors.lastname: Meyer
authors.forename: C
authors.initials: C
authors.lastname: Mazurier
authors.forename: J
authors.initials: J
authors.lastname: Goudemand
authors.forename: J
authors.initials: J
authors.lastname: Ingerslev
authors.forename: D
authors.initials: D
authors.lastname: Habart
authors.forename: Z
authors.initials: Z
authors.lastname: Vorlova
authors.forename: L
authors.initials: L
authors.lastname: Holmberg
authors.forename: S
authors.initials: S
authors.lastname: Lethagen
authors.forename: J
authors.initials: J
authors.lastname: Pasi
authors.forename: F
authors.initials: F
authors.lastname: Hill
authors.forename: I
authors.initials: I
authors.lastname: Peake
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019281:Dimerization; D005060:Europe; D005192:Family Health; D005838:Genotype; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation; D014842:von Willebrand Diseases / Q000145:classification / Q000175:diagnosis* / Q000453:epidemiology; D014841:von Willebrand Factor / Q000032:analysis* / Q000737:chemistry / Q000235:genetics
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor