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Hamostaseologie 2017; 37(01): 53-57
DOI: 10.5482/HAMO-16-10-0040
State of the art
Schattauer GmbH

Plasma-derived versus recombinant factor concentrates in PUPs: a never ending debate?

Plasmatische versus rekombinante Faktoren- konzentrate bei nicht vorbehandelten Patienten: eine niemals endende Debatte?
Erik Berntorp
1   Centre for Thrombosis and Hemostasis, Lund University, Skane University Hospital, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

received: 07 October 2016

accepted in revised form: 14 November 2016

Publication Date:
28 December 2017 (online)

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Summary

Inhibitor development in haemophilia is a serious complication to treatment with factor concentrates. Since the advent of more pure products, especially developed using recombinant DNA technology, some studies have shown an increased incidence of inhibitors in previously untreated patients (PUPs) receiving recombinant products whereas plasma-derived concentrates sometimes have been claimed to have a protective role, probably due to the content of von Willebrand factor (VWF). In fact, experiments indicate that the VWF may block uptake of factor VIII into macrophages for further processing to the immune system. Also, a competition between VWF and inhibitor binding to the C2 domain of factor VIII has been suggested. Recently, large cohort and surveillance studies have created a vigorous debate about the role of product class for inhibitor development as results have been conflicting. The only randomised prospective study, the SIPPET study, was published in 2016, and substantiated previous reports claiming that plasma derived concentrates give less inhibitors in patients with severe haemophilia A, previously not exposed to factor VIII. The debate will continue.

Zusammenfassung

Die Entwicklung von Inhibitoren bei Hämophilie ist eine ernsthafte Komplikation bei der Behandlung mit Faktorkonzentraten. Seit der Einführung von Produkten mit einem höheren Reinheitsgrad, wurde in einigen Studien unter Anwendung von rekombinanten Präparaten bei nicht vorbehandelten Patienten ein gehäuftes Auftreten von Inhibitoren beobachtet. Dahingegen wurde gelegentlich von plasmatischen Konzentraten behauptet, sie hätten – vermutlich aufgrund ihres Gehalts an von-Willebrand-Faktor (VWF) – eine protektive Funktion. Tatsächlich gibt es experimentelle Hinweise, dass der VWF die Aufnahme von Faktor VIII in Makrophagen blockiert, wo er für das Immunsystem weiter verarbeitet wird. Auch wurde angenommen, dass VWF und Inhibitoren um die Bindung an der C2-Domäne des Faktors VIII konkurrieren. Jüngst haben große Kohorten- und Observationsstudien infolge ihrer widersprüchlichen Ergebnisse eine lebhafte Debatte über die Rolle der Produktklassen bei der Entstehung von Inhibitoren entfacht. Die einzige randomisierte prospektive Studie (SIPPET) wurde 2016 publiziert und hat frühere Berichte bestätigt, in denen die These aufgestellt wurde, dass mit den plasmatischen Konzentraten bei Patienten mit schwerer Hämophilie A ohne vorherige Exposition gegenüber Faktor VIII weniger Inhibitoren entstehen. Die Diskussion wird weitergehen. mit Faktorkonzentraten. Seit der Einführung von Produkten mit einem höheren Reinheitsgrad, wurde in einigen Studien unter Anwendung von rekombinanten Präparaten bei nicht vorbehandelten Patienten ein gehäuftes Auftreten von Inhibitoren beobachtet. Dahingegen wurde gelegentlich von plasmatischen Konzentraten behauptet, sie hätten – vermutlich aufgrund ihres Gehalts an von-Willebrand-Faktor (VWF) – eine protektive Funktion. Tatsächlich gibt es experimentelle Hinweise, dass der VWF die Aufnahme von Faktor VIII in Makrophagen blockiert, wo er für das Immunsystem weiter verarbeitet wird. Auch wurde angenommen, dass VWF und Inhibitoren um die Bindung an der C2-Domäne des Faktors VIII konkurrieren. Jüngst haben große Kohorten- und Observationsstudien infolge ihrer widersprüchlichen Ergebnisse eine lebhafte Debatte über die Rolle der Produktklassen bei der Entstehung von Inhibitoren entfacht. Die einzige randomisierte prospektive Studie (SIPPET) wurde 2016 publiziert und hat frühere Berichte bestätigt, in denen die These aufgestellt wurde, dass mit den plasmatischen Konzentraten bei Patienten mit schwerer Hämophilie A ohne vorherige Exposition gegenüber Faktor VIII weniger Inhibitoren entstehen. Die Diskussion wird weitergehen.

Keywords

haemophilia - inhibitor - factors concentrate - previously untreated patients

Schlüsselwörter

Hämophilie - Inhibitor - Faktorenkonzentrat - nicht vorbehandelte Patienten
 

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