Klassifikation des von-Willebrand-Syndroms

Zusammenfassung

Das von-Willebrand-Syndrom (VWS) ist bekannt für seine ausgesprochene Heterogenität, die sich in der klinischen Symptomatik und Pathophysiologie ausdrückt. Grundlage der phänotypischen Differenzierung sind quantitative und qualitative Unterschiede des von-Willebrand-Faktors (VWF) sowie seine multimere Struktur. Nach Einführung der Multimeranalyse des VWF wurden eine Vielzahl verschiedener Subtypen des VWS beschrieben, die sich im elektrophoretischen Wanderungsverhalten der VWF-Multimere unterschieden. Eine erste Klassifikation von Ruggeri und Zimmerman 1987 war mehr eine Sammlung der verschiedenen Phänotypen als eine systematische Einteilung, da die zu Grunde liegenden Strukturanomalien des VWF nicht bekannt waren. Die genauere Beschreibung diverser funktioneller Defekte des VWF ermöglichte dann eine Revision der ersten Klassifikation durch Sadler 1994, die vor allem das Ziel einer Vereinfachung der Klassifikation hatte und auf die klinisch relevanten Unterschiede fokussierte. Zu diesem Zeitpunkt waren jedoch viele molekulare Ursachen des VWS nicht bekannt. Die Einführung molekularer Techniken und die Analyse des VWF ermöglicht seitdem exakte Genotyp/Phänotyp-Korrelationen, die eine sichere Basis für eine verbesserte Klassifikation des VWS bieten.

Summary

Von Willebrand disease (VWD) is known for its marked heterogeneity which was already recognized by von Willebrand in 1926. The basis of phenotypic differentiation are quantitative and qualitative or functional differences between the different types and subtypes of VWD. One of the most important tools in the classification of VWD is multimer analysis that visualizes many of the structural abnormalities of mutant VWF. The introduction of multimer analysis was followed by the identification of an increasing number of different VWD phenotypes that were first reviewed in 1987 by Ruggeri and Zimmerman, thus forming a first classification of the disease. However, the detection of additional phenotypes required a revision of the nomenclature at a time point when only a few types of VWD had already been analyzed on the molecular level. Consequently, the molecular data only played a minor role in the revised classification published by Sadler in 1994. The advent of molecular techniques provided the opportunity for genotype/phenotype studies which recently helped not only to elucidate or confirm important functions of VWF and its steps of 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 soundly based classification of VWD, equally useful for the clinician and for research requirements.

Schlüsselwörter

Von-Willebrand-Syndrom

Keywords

Von Willebrand disease

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