Current treatment of von Willebrand’s disease

Zusammenfassung

Fortschritte im Verständnis der Pathophysiologie, verbesserte diagnostische Techniken und Erfahrungen in den Erfordernissen der Therapie während der vergangenen 20 bis 25 Jahre haben zu deutlichen Verbesserungen der Sicherheit der Diagnose und der Lebensqualität von Patienten mit von Willebrand-Syndrom (VWS) geführt. Die wissenschaftlichen Erkenntnisse aus dieser Zeit haben dazu geführt, dass das VWS zurzeit als eine extrem heterogene Erkrankung gilt. Für einige Subtypen des VWS konnten die qualitativen Veränderungen des von-Willebrand-Faktors (VWF) eindeutig auf den zugrundeliegenden Gendefekt zurückgeführt werden, während dieses für andere Subtypen nicht gelungen ist. Für die häufigste Form, als Typ 1 bezeichnet, korreliert die Verminderung des VWF mit dem Funktionsverlust. Hier stehen wir allerdings erst in der Anfangsphase der Aufklärung der kausalen Gendefekte.

Behandlungsgrundlagen, welche die Kriterien evidenzbasierter Richtlinien erfüllen, existieren nicht. Daher stützen sich die Therapiestrategien weitgehend auf Empirie. Die Basis dieser Übersichtsarbeit über Therapiemodalitäten bei VWS-Patienten beruht auf der aktuellen Literatur und der klinischen Erfahrung der Autoren. Es ist unsere Absicht, die Fragen aufzuzeigen, die zurzeit bezüglich der Therapie in Abhängigkeit von der VWS-Subtypisierung diskutiert werden. Über die aktuellen Therapieoptionen auf pharmakologischer Basis oder mittels Substitution hinaus, sollen auch solche aufgezeigt werden, die sich vielleicht schon in naher Zukunft ergeben können.

Summary

During the last couple of decades improved pathophysiological insight, use of improved diagnostic tools, and improved understanding of treatment requirements, have converged on an improved safety of treatment and quality of life for the patient suffering VWD. The scientific development in this area has elucidated a vast heterogeneity in VWD now appreciated as a vastly heterogeneous group of bleeding disorders. In some subtypes, dysfunctional VWF protein characteristics are clarified and logically linked with the distinct site of the VWF gene mutation abolishing specific functions of VWF, while in other subtypes such relationships have not yet been established. With the most frequently occurring variant, designated type 1, the quantitative loss in VWF seems to correlate with its reduced function. However, we are only at the beginning of the era of molecular genetics of this specific variant.

Medical evidence based guidelines by ordinary standards for treatment of VWD do not exist. Therefore, treatment is based on a mechanistic approach and empirical knowledge. The review presented here focuses on the management of bleeding in VWD. Its basis is a mixture of data reported to literature and the authors’ personal clinical observations. Our intention is the presentation and discussion of current issues related to VWD as well as the various pharmaceutical treatment options available for patients afflicted with von Willebrand’s disease, together with some theoretical thoughts on possible future modalities.

Schlüsselwörter

Von-Willebrand-Syndrom - DDAVP - Ristocetin-Kofaktor - Faktor-VIII-Konzentrat - Antifibrinolytika

Keywords

von Willebrands disease - DDAVP - ristocetin cofactor - factor VIII concentrate - antifibrinolytics

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