title: Impact of plasma von Willebrand factor levels in the diagnosis of type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1VWD).
abstract: BACKGROUND
  Presence of bleeding symptoms, inheritance and reduced von Willebrand factor (VWF) contribute to the diagnosis of type 1 von Willebrand disease (VWD). However, quantitative analysis of the importance of VWF antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo) levels in the diagnosis is lacking.
  
  
  OBJECTIVE
  To evaluate the relative contribution of VWF measurement to the diagnosis of VWD.
  
  
  METHODS
  From the MCMDM-1VWD study cohort, 204 subjects (considered as affected by VWD based on the enrolling Center diagnoses and the presence of linkage with the VWF locus) were compared with 1155 normal individuals. Sensitivity, specificity and diagnostic positive likelihood ratios (LR) of VWF:Ag and VWF:RCo were computed.
  
  
  RESULTS
  ABO blood group was the variable most influencing VWF levels, but adjustment of the lower reference limit for the ABO group did not improve sensitivity and specificity of VWF:Ag or VWF:RCo. The lower reference limit (2.5th percentile) was 47 IU dL(-1) for both VWF:Ag and VWF:RCo and showed similar diagnostic performance [receiver-operator curve area: 0.962 and 0.961 for VWF:Ag and VWF:RCo, respectively; P = 0.81]. The probability of VWD was markedly increased only for values below 40 IU dL(-1) (positive LR: 95.1 for VWF:Ag), whereas intermediate values (40 to 60 IU dL(-1)) of VWF only marginally indicated the probability of VWD.
  
  
  CONCLUSIONS
  Although the conventional 2.5 lower percentile has good sensitivity and specificity, only VWF:Ag or VWF:RCo values below 40 IU dL(-1) appear to significantly indicate the likelihood of type 1 VWD. The LR profile of VWF level could be used in a diagnostic algorithm.
authors.affiliation: San Bortolo Hospital, Vicenza, Italy. rodeghiero@hemato.ven.it
authors.forename: A
authors.initials: A
authors.lastname: Tosetto
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: M
authors.initials: M
authors.lastname: Bernardi
authors.forename: K
authors.initials: K
authors.lastname: Bertoncello
authors.forename: A
authors.initials: A
authors.lastname: Goodeve
authors.forename: A B
authors.initials: AB
authors.lastname: Federici
authors.forename: J
authors.initials: J
authors.lastname: Batlle
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: Eikenboom
authors.forename: R
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: J
authors.initials: J
authors.lastname: Ingerslev
authors.forename: Z
authors.initials: Z
authors.lastname: Vorlova
authors.forename: D
authors.initials: D
authors.lastname: Habart
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: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014842:von Willebrand Diseases / Q000097:blood* / Q000175:diagnosis*; D014841:von Willebrand Factor / Q000096:biosynthesis*
chemical_list: D014841:von Willebrand Factor