Standardisierte Diagnostik des von-Willebrand-Syndroms

Zusammenfassung

Das von-Willebrand-Syndrom (VWS) wird verursacht durch einen quantitativen und/oder qualitativen Defekt des von-Willebrand-Faktors (VWF), einem hochmolekularen multimeren Glykoprotein. Typisch ist ein Defekt der primären Hämostase mit Blutungssymptomen, die denen bei thrombozytären Störungen gleichen. Der VWF hat zwei Funktionen: Er ist für die Adhäsion von Thrombozyten an verletzten Gefäßen verantwortlich und er stabilisiert den FVIII im Plasma. Wegen der Komplexität der Gerinnungsstörung sind Diagnose und Klassifizierung des VWS eine Herausforderung für jedes Gerinnungslabor. Die Stufendiagnostik bei Verdacht auf ein VWS besteht aus Eigen- und Familienanamnese, orientierenden Untersuchungen (Blutungszeit, Filter-Testen, Thrombozytenzahl, aPTT), erweiterten Testen (VWF:Ag, VWF:RCo, VIII:C) und spezieller Diagnostik (VWF:CB, RIPA-Test, Multimeranalyse, VWF:FVIIIB, thrombozytärer VWF).

Verbessertes Verständnis der klinischen Phänotypen und der pathophysiologischen Grundlagen gaben Anlass zu einer VWS-Klassifizierung, die zwischen quantitativen und qualitativen Defekten des VWF-Moleküls unterschied. Diese beruhte auf der Darstellung struktureller Eigenschaften mittels Auftrennung des VWF im elektrischen Feld. Deutliche Fortschritte der molekularen Techniken erlaubten die Untersuchung von Phänotyp/ Genotyp-Relationen. Hierdurch konnten funktionelle Eigenschaften des VWF aufgeklärt werden sowie viele Gendefekte, die ein VWS verursachen können.

Summary

Von Willebrand disease (VWD) is caused by quantitative and/or qualitative defects of the von Willebrand factor (VWF), a multimeric high molecular glycoprotein. Typically, it affects the primary haemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a functional platelet defect. The VWF promotes its function in two ways: It promotes platelet adhesion to the injured vessel wall under conditions of high shear forces and it functions as carrier for factor VIII in plasma. Due to its complexity diagnosis of VWD is one of the most challenging of coagulation disorders. The stepwise diagnosis of VWD includes patient’s and family history, orientating procedures (bleeding time, filter tests, platelet count, aPTT), confirmatory tests (VWF:Ag, VWF:RCo, VIII:C) and tests for final classification (VWF:CB, RIPA, multimeric analysis, bWF:FVIIIB, platelet VWF).

Accumulating knowledge of the different clinical phaenotypes and their pathophysiological basis was translated into a classification scheme that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters and by analyzing the electrophoretic pattern of VWF multimers. The advent of molecular techniques provided the opportunity for genotype/phaenotype studies which recently helped not only to elucidate or confirm important functions of VWF and the steps of its posttranslational processing but also many disease causing defects.

Schlüsselwörter

Von-Willebrand-Syndrom - von-Willebrand-Faktor

Keywords

Von Willebrand disease - von Willebrand factor

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