title: No increase in bleeding identified in type 1 VWD subjects with D1472H sequence variation.
abstract: The diagnosis of von Willebrand disease (VWD) is complicated by issues with current laboratory testing, particularly the ristocetin cofactor activity assay (VWF:RCo). We have recently reported a sequence variation in the von Willebrand factor (VWF) A1 domain, p.D1472H (D1472H), associated with a decrease in the VWF:RCo/VWF antigen (VWF:Ag) ratio but not associated with bleeding in healthy control subjects. This report expands the previous study to include subjects with symptoms leading to the diagnosis of type 1 VWD. Type 1 VWD subjects with D1472H had a significant decrease in the VWF:RCo/VWF:Ag ratio compared with those without D1472H, similar to the findings in the healthy control population. No increase in bleeding score was observed, however, for VWD subjects with D1472H compared with those without D1472H. These results suggest that the presence of the D1472H sequence variation is not associated with a significant increase in bleeding symptoms, even in type 1 VWD subjects.
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. vflood@mcw.edu
authors.forename: Veronica H
authors.initials: VH
authors.lastname: Flood
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Friedman
authors.forename: Joan Cox
authors.initials: JC
authors.lastname: Gill
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Haberichter
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Christopherson
authors.forename: Brian R
authors.initials: BR
authors.lastname: Branchford
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Hoffmann
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Abshire
authors.forename: Amy L
authors.initials: AL
authors.lastname: Dunn
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Di Paola
authors.forename: W Keith
authors.initials: WK
authors.lastname: Hoots
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Brown
authors.forename: Cindy
authors.initials: C
authors.lastname: Leissinger
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Lusher
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Ragni
authors.forename: Amy D
authors.initials: AD
authors.lastname: Shapiro
authors.forename: Robert R
authors.initials: RR
authors.lastname: Montgomery
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D006470:Hemorrhage / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D006801:Humans; D015994:Incidence; D020125:Mutation, Missense; D012107:Research Design; D012720:Severity of Illness Index; D056725:von Willebrand Disease, Type 1 / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D014841:von Willebrand Factor; D001224:Aspartic Acid; D006639:Histidine