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Hamostaseologie 2019; 39(04): 326-338
DOI: 10.1055/s-0039-1692688
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Replacement Therapy in Patients with Von Willebrand Disease—Indications and Monitoring

Die Substitutionsbehandlung des von-Willebrand-Syndroms—Indikationen und Monitoring
Ulrike Nowak-Göttl
1   Department of Clinical Chemistry, Thrombosis and Hemostasis Unit, University Hospital of Kiel and Lübeck, Kiel, Germany
,
Wolfgang Miesbach
2   Medical Clinic II, Institute of Transfusion Medicine, Goethe University, Frankfurt, Germany
,
Jürgen Koscielny
3   Institute of Transfusion Medicine, Charité - University Medicine, Berlin, Germany
,
Carl-Erik Dempfle
4   Coagulation Center Mannheim, Mannheim, Germany
,
Marc Maegele
5   Department of Trauma and Orthopedic Surgery, Cologne-Merheim Medical Center, University of Witten/Herdecke, Cologne, Germany
,
Mario von Depka Prondzinski
6   Werlhof-Institute Hannover, Hannover, Germany
,
Dagmar Westrup
7   Arnold-Heller-Str. 3, buiding 17, 24105 Kiel, Bad Camberg, Germany
,
Michael Spannagl
8   Department of Hemostasis and Transfusion Medicine, Ludwig-Maximilians University, Munich, Germany
› Author Affiliations
Further Information

Publication History

30 October 2018

13 May 2019

Publication Date:
30 July 2019 (online)

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Abstract

In patients with von Willebrand disease (VWD), replacement therapy may be indicated in the case of spontaneous bleeding, surgical interventions and injuries/trauma or as a prophylaxis of spontaneous bleeding episodes. The deficient von Willebrand factor (VWF) is replaced with or without factor VIII (FVIII). Dual VWF/FVIII concentrates can be beneficial in the case of low FVIII level, while repeated dosing may lead to very high FVIII levels, with a potential thrombogenic effect in individual VWD patients. An excessive FVIII:C increase can be limited by using a VWF product with a low level of FVIII, achieving a haemostatic adequate FVIII:C increase after 6 to 12 hours. Replacement therapy in patients with VWD shall be individualised considering VWD type, history and risk of bleeding and risk of thrombosis, as well as indication and the individually variable VWF and FVIII increase. Deviations from the dosages and minimum trough levels mentioned in guidelines or recommendations can be considered in justified cases. The objective of this review is to provide recommendations for specific constellations of replacement therapy based on the VWD-specific guidelines available in Europe, the available evidence, own experiences and the consensus of the interdisciplinary German author group.

Zusammenfassung

Bei Patienten mit von-Willebrand-Krankheit (VWD) kann eine Ersatztherapie bei spontanen Blutungen, chirurgischen Eingriffen und Verletzungen/Traumata oder zur Prophylaxe spontaner Blutungen angezeigt sein. Der mangelnde von Willebrand-Faktor (VWF) wird mit oder ohne Faktor VIII (FVIII) ersetzt. Duale VWF/FVIII-Konzentrate können bei niedrigem FVIII-Spiegel von Vorteil sein, während eine wiederholte Gabe zu sehr hohen FVIII-Spiegeln führen kann, die bei einzelnen VWD-Patienten einen potenziellen thrombogenen Effekt haben können. Ein übermäßiger Anstieg von FVIII:C kann durch die Verwendung eines VWF-Produkts mit einem niedrigen FVIII-Gehalt begrenzt werden, wodurch nach 6 bis 12 Stunden ein hämostatisch adäquater Anstieg von FVIII:C erreicht wird. Die Ersatztherapie bei Patienten mit VWD ist unter Berücksichtigung des VWD-Typs, der Vorgeschichte, des Blutungsrisikos und des Thromboserisikos sowie der Indikation und des individuell variablen Anstiegs von VWF und FVIII zu individualisieren. Abweichungen von den in Richtlinien oder Empfehlungen genannten Dosierungen und Mindest-Talspiegeln können in begründeten Fällen berücksichtigt werden. Ziel dieser Übersichtsarbeit ist es, Empfehlungen für spezifische Konstellationen der Ersatztherapie auf der Grundlage der in Europa verfügbaren VWD-spezifischen Leitlinien, der verfügbaren Evidenz, der eigenen Erfahrungen und des Konsenses der interdisziplinären deutschen Autorengruppe zu geben.

Keywords

von Willebrand disease - von Willebrand factor - factor VIII - replacement therapy - bleeding

Schlüsselwörter

von-Willebrand-Syndrom - von-Willebrand-Faktor - Faktor VIII - Substitutionstherapie - Blutung
 

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