Acquired von Willebrand syndrome 2004: International Registry

Summary

The acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease. Unlike the congenital form, AVWS usually occurs in individuals with no personal or family history of bleeding. Large studies on AVWS are not available, diagnosis remains difficult and treatment empirical. Acquired von Willebrand syndrome is especially frequent in lympho- or myeloproliferative disorders. It is associated with solid tumours, immunological and cardiovascular disorders as well as other miscellaneous conditions. Diagnosis of AVWS is based on assays measuring ristocetin cofactor activity or collagen binding, which are usually abnormally low, while factor VIII coagulant activity is sometimes within the reference range. FVIII/VWF inhibiting activities are found in only a minority of cases. Bleeding episodes in patients with AVWS are mostly of the mucocutaneous type and can be managed with desmopressin, plasma-derived factor VIII/von Willebrand factor (FVIII/VWF) concentrates and intravenous immunoglobulin. Recombinant activated factor VII can be useful in cases unresponsive to standard therapy. In conclusion, the AVWS, although rare, is certainly underestimated in clinical practice: The actual clinical impact of AVWS should be evaluated by prospective studies. The authors are co-ordinating an updated version of the International Registry on AVWS that will allow data to be entered directly online.

Zusammenfassung

Das erworbene von-Willebrand-Syndrom (VWS) ist eine seltene Erkrankung, die sich laboranalytisch nicht vom angeborenen VWS unterscheiden lässt. Eindeutig different von der angeborenen Form sind das meist deutlich spätere Manifestationsalter sowie die negative Familienanamnese. Größere Studien, die sich mit allen Formen des erworbenen VWS befassen, sind nicht publiziert, die Diagnose ist oftmals schwierig und die Behandlungsmodalitäten sind mehr oder weniger empirisch aufgrund der unbefriedigenden Datenlage. Die Literatur und eine weltweite Umfrage finden die meisten Fälle bei Patienten mit lympho- und myeloproliferativen Erkrankungen. Daneben tritt es noch bei soliden Tumoren und immunologischen Erkrankungen auf, häufiger bei kardiovaskulären Erkrankungen und assoziiert mit einer Reihe anderer, untereinander nicht verwandter klinischer Situationen. Diagnostisch sind erniedrigte funktionelle Parameter des von-Willebrand-Faktors (VWF:RCo und VWF:CB) wegweisend, nicht selten mit normalem oder wenig erniedrigtem VWF:Ag. Häufig liegt die FVIII-Aktivität im Referenzbereich. Die Suche nach Antikörpern gegen den von-Willebrand-Faktor (VWF) ist selten erfolgreich. Die Blutungssymptome ähneln denen von Patienten mit angeborenem VWS. Sie können erfolgreich mit Desmopressin, FVIII/VWF-Konzentraten oder intravenösen Immunglobulinen therapiert werden. Ist hiermit die Situation nicht beherrschbar, bleibt aktivierter rekombinanter FVII. Derzeit ist davon auszugehen, dass das erworbene VWS zwar selten, jedoch eindeutig unterdiagnostiziert ist. Daher sind weitere prospektive Studien notwendig, die sich mit den klinischen Folgen des erworbenen VWS befassen. Die Autoren werden Anfang 2004 eine aktualisierte Fassung des International Registry on AVWS auflegen, das eine direkte Online-Eingabe neu entdeckter Fälle ermöglichen soll.

Keywords

Acquired von Willebrand syndrome - von Willebrand factor - lymphoproliferative disorders - myeloproliferative disorders - solid tumours

Schlüsselwörter

Erworbenes von-Willebrand-Syndrom - von-Willebrand-Faktor - lymphoproliferative Erkrankungen - myeloproliferative Erkrankungen - solide Tumoren

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