Practical Guidance of the GTH Haemophilia Board on the Use of Emicizumab in Patients with Haemophilia A

Katharina Holstein; Manuela Albisetti; Christoph Bidlingmaier; Susan Halimeh; Sabine Heine; Robert Klamroth; Christoph Königs; Karin Kurnik; Christoph Male; Johannes Oldenburg; Werner Streif; Cornelia Wermes; Carmen Escuriola-Ettingshausen; on behalf of the ‘Ständige Kommission Hämophilie’ (Haemophilia board) of the German, Swiss Austrian Society for Thrombosis Haemostasis Research (GTH)

doi:10.1055/a-1127-6476

Hämostaseologie, Table of Contents

Hamostaseologie 2020; 40(05): 561-571
DOI: 10.1055/a-1127-6476

Review Article

Practical Guidance of the GTH Haemophilia Board on the Use of Emicizumab in Patients with Haemophilia A

Katharina Holstein

¹Haematology and Clinical Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

,

Manuela Albisetti

²Division of Hematology, University Children's Hospital, Zurich, Switzerland

,

Christoph Bidlingmaier

³Centre for Development and Complex Chronic Diseases in Children (iSPZHauner), Department of Paediatrics, Paediatric Haemophilia Centre, LMU Munich, Munich, Germany

,

Susan Halimeh

⁴Coagulation Center Rhein-Ruhr, Duisburg, Germany

,

Sabine Heine

⁵Department of Paediatric Oncology/Haematology, Saarland University Hospital, Homburg, Germany

,

Robert Klamroth

⁶Internal Medicine, Angiology and Haemostaseology, Haemophilia Centre, Vivantes Hospital Friedrichshain, Berlin, Germany

,

Christoph Königs

⁷Department of Paediatrics and Adolescent Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany

,

Karin Kurnik

⁸Paediatric Haemophilia Centre, Department of Paediatrics, LMU Munich, Munich, Germany

,

Christoph Male

⁹Department of Paediatrics, Medical University of Vienna, Vienna, Austria

,

Johannes Oldenburg

¹⁰Institute for Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany

,

Werner Streif

¹¹Department of Paediatrics 1, Medical University of Innsbruck (MUI), Innsbruck, Austria

,

Cornelia Wermes

¹²Haemophilia Center, Werlhof-Institute, Hannover, Germany

,

Carmen Escuriola-Ettingshausen

¹³Haemophilia Center Rhine Main, HZRM, Mörfelden-Walldorf, Germany

,

on behalf of the ‘Ständige Kommission Hämophilie’ (Haemophilia board) of the German, Swiss Austrian Society for Thrombosis Haemostasis Research (GTH)

› Author Affiliations

Abstract

Emicizumab has been approved for bleeding prophylaxis in patients with haemophilia A (PWHAs) with or without inhibitors. Because of substantial differences between factor VIII (FVIII) and Emicizumab, the ‘Ständige Kommission Hämophilie’ of the German, Austrian, Swiss Society for Thrombosis and Haemostasis Research (GTH) established a practical guidance for the use of Emicizumab in PWHAs. A systematic literature research was conducted in PubMed. Based on this and on personal experience, this practical guidance has been developed. Each single statement has been discussed among members of the ‘Ständige Kommission Hämophilie’ and revised accordingly. The final set of recommendations has been approved by all authors analogous to the Delphi method. This practical guidance is provided for physicians treating PWHAs with regard to general aspects, patient education, bleeding treatment, surgery, use of Emicizumab in previously untreated patients (PUPs), patients with newly diagnosed inhibitors and elderly patients. Patients should be treated in expert centres and adequate laboratory tests to monitor Emicizumab levels, FVIII replacement and inhibitors should be available. Early experience of immune tolerance induction protocols integrating Emicizumab is reviewed, and the limited experience in PUPs and very young children is described. So far, no thromboembolic complications have been reported with the concomitant use of FVIII or recombinant activated FVII for bleeding treatment or surgery. Activated prothrombin complex concentrate doses of >100 U/kg for >24 hours should be avoided whenever possible because of the high risk of thrombosis and/or thrombotic microangiopathy. In conclusion, this study is designed to support haemophilia physicians using Emicizumab in physicians treating hemophilia and using (PWHAs). With further post-marketing experience and trials, regular updates are necessary.

Zusammenfassung

Einleitung Emicizumab, ein bispezischer Antikörper, der wie aktivierter Faktor VIII (FVIII) wirkt, ist zugelassen zur Blutungsprophylaxe bei Patienten mit Hämophilie A ohne und mit FVIII-Inhibitor. Aufgrund substanzieller Unterschiede zwischen Emicizumab und FVIII hat die „Ständige Kommission Hämophilie“ der deutschen, österreichischen und schweizerischen Gesellschaft für Thrombose- und Hämostaseforschung (GTH) beschlossen, einen praxisorientierten Leitfaden für den Einsatz von Emicizumab bei Patienten mit Hämophilie A (PWHA) zu entwickeln.

Methoden Daten aus der Literatur (systematische Literaturrecherche in PubMed) und persönliche Erfahrungen wurden zusammengetragen und daraus Empfehlungen entwickelt. Diese wurden in der „Ständigen Kommission Hämophilie“ diskutiert und entsprechend revidiert. Die finalen Empfehlungen wurden von allen Autoren mittels Delphi-Abstimmung freigegeben.

Ergebnisse Die Empfehlungen beziehen sich auf Patienten ohne und mit FVIII-Inhibitor und beinhalten generelle Aspekte, Patientenaufklärung, Blutungsbehandlung, Operationen, Anwendung von Emicizumab bei zuvor unbehandelten Patienten (PUPs), Patienten mit neudiagnostizierten Inhibitoren und älteren Patienten. Patienten sollten in spezialisierten Behandlungszentren behandelt werden und adäquate Labortests zum Monitoring von Emicizumab, einer Faktor VIII-Substitution oder von FVIII-Inhibitoren sollten zur Verfügung stehen. Erste Erfahrungen mit Protokollen zu Immuntoleranz -Induktion in Kombination mit Emicizumab und die begrenzte Erfahrung mit sehr jungen Kindern wird berichtet. Bis jetzt wurden keine thrombotischen Komplikationen bei der zusätzlichen Blutungsbehandlung mit rFVIIa oder FVIII berichtet. aPCC-Dosierungen von > 100 U/kg über > 24 Stunden müssen vermieden werden, wegen des Risikos von Thrombosen und/oder thrombotischer Mikroangiopathien.

Schlussfolgerung Die Empfehlungen wurden anhand der aktuell verfügbaren Erfahrung entwickelt als Leitfaden für Hämophiliebehandler, die Emicizumab bei PWHA einsetzen. Mit weiterer Erfahrung und neuen Studien ist ein regelmäßiges Überarbeiten der Empfehlungen erforderlich.

Keywords

Emicizumab - haemophilia A - inhibitors - prophylaxis

Schlüsselwörter

Emicizumab - Haemophilia A - Inhibitoren - Prophylaxe

Full Text

References

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