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)
(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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- author
- organization
- publishing date
- 2008
- 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
- Elsevier
- 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)
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- 2034128f-713b-4926-a733-7766bbac5c96 (old id 1206255)
- date added to LUP
- 2016-04-01 11:50:31
- date last changed
- 2025-01-14 20:41:06
@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 = {{Elsevier}},
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}},
}