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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)

Budde, U ; Schneppenheim, R ; Eikenboom, J ; Goodeve, A ; Will, K ; Drewke, E ; Castaman, G ; Rodeghiero, F ; Federici, A B and Batlle, J , et al. (2008) In Journal of Thrombosis and Haemostasis 6(5). p.762-771
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. Patients and 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... (More)
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. Patients and 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
von Willebrand disease, type 1, multimer analysis, mutation, von, Willebrand factor
in
Journal of Thrombosis and Haemostasis
volume
6
issue
5
pages
762 - 771
publisher
Wiley-Blackwell
external identifiers
  • wos:000254991400009
  • scopus:42149120672
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2008.02945.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Paediatrics (Lund) (013002000)
id
2034128f-713b-4926-a733-7766bbac5c96 (old id 1206255)
date added to LUP
2016-04-01 11:50:31
date last changed
2022-02-03 05:51:51
@article{2034128f-713b-4926-a733-7766bbac5c96,
  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. Patients and 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.}},
  author       = {{Budde, U and Schneppenheim, R and Eikenboom, J and Goodeve, A and Will, K and Drewke, E and Castaman, G and Rodeghiero, F and Federici, A B and Batlle, J and Perez, A and Meyer, D and Mazurier, C and Goudemand, J and Ingerslev, J and Habart, D and Vorlova, Z and Holmberg, Lars and Lethagen, Stefan and Pasi, J and Hill, F and Peake, I}},
  issn         = {{1538-7933}},
  keywords     = {{von Willebrand disease; type 1; multimer analysis; mutation; von; Willebrand factor}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{762--771}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Thrombosis and Haemostasis}},
  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)}},
  url          = {{http://dx.doi.org/10.1111/j.1538-7836.2008.02945.x}},
  doi          = {{10.1111/j.1538-7836.2008.02945.x}},
  volume       = {{6}},
  year         = {{2008}},
}