title: A molecular approach to the classification of von Willebrand disease.
abstract: The marked heterogeneity of von Willebrand disease was already recognized by von Willebrand in 1926. The accumulating knowledge of the different clinical phenotypes and the pathophysiological basis of the disease was translated into a classification that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters and by analysing the electrophoretic pattern of von Willebrand factor multimers. The increasing number of different von Willebrand disease phenotypes required a revision of the nomenclature at a time when only a few types of von Willebrand disease had already been analysed at the molecular level. Consequently, the molecular data played only a minor role in the revised classification. Given the pronounced, even intra-individual, variation in the manifestation of von Willebrand disease and the diagnostic difficulties caused by a non-standardized methodology, it is clear that biochemical methods alone are insufficient for a clear classification. The advent of molecular techniques provided the opportunity for genotype-phenotype studies that recently helped to elucidate or confirm not only the important functions of von Willebrand factor and the steps of its post-translational processing, but also many disease-causing defects. The reproducible correlation between certain phenotypes and particular mutations can now be used for a molecular approach towards a final classification of von Willebrand disease, equally useful for the clinician and for research requirements.
authors.affiliation: Department of Paediatric Haematology and Oncology, University Hospital Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: Z M
authors.initials: ZM
authors.lastname: Ruggeri
mesh_terms: D014644:Genetic Variation; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D010641:Phenotype; D014842:von Willebrand Diseases / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*