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)
| Autor: | U. Budde, Claudine Mazurier, Javier Batlle, Lars Holmberg, Giancarlo Castaman, A Perez, Jeroen Eikenboom, Jenny Goudemand, Zdena Vorlova, E. Drewke, K. Will, Reinhard Schneppenheim, Francesco Rodeghiero, Stefan Lethagen, Anne Goodeve, David Habart, Frank Hill, John Pasi, Ian R. Peake, Augusto B. Federici, Dominique Meyer, Jørgen Ingerslev |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Genotype Antigen Von Willebrand factor hemic and lymphatic diseases von Willebrand Disease von Willebrand Factor Von Willebrand disease Epidemiology Molecular Medicine Humans In patient Congenital Bleeding Disorder Genotyping Family Health Molecular Epidemiology biology business.industry Case-control study Hematology medicine.disease Europe von Willebrand Diseases Multimer analysis Mutation Type 1 von Willebrand disease von Willebrand factor Case-Control Studies Immunology biology.protein Biological Markers business Dimerization Settore MED/15 - Malattie del Sangue Biomarkers circulatory and respiratory physiology |
| Zdroj: | Budde, U, Schneppenheim, R, Eikenboom, J, Goodeve, A, Will, K, Drewke, E, Castaman, G, Rodeghiero, F, Federici, A B, Batlle, J, Pérez, A, Meyer, D, Mazurier, C, Goudemand, J, Ingerslev, J, Habart, D, Vorlova, Z, Holmberg, L, Lethagen, S, Pasi, J, Hill, F & Peake, I 2008, ' 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) ', Journal of Thrombosis and Haemostasis, vol. 6, no. 5, pp. 762-71 . https://doi.org/10.1111/j.1538-7836.2008.02945.x |
| DOI: | 10.1111/j.1538-7836.2008.02945.x |
| Popis: | Udgivelsesdato: 2008-May 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. |
| Databáze: | OpenAIRE |
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