Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients.

Abstract

The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment-related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy. Antibody eradication, by way of immune tolerance induction (ITI), is still the preferred management strategy for treating patients with inhibitors. This approach is successful in most patients, but some are difficult to tolerise and/or are unresponsive to ITI, and they represent the most complicated patients to treat. However, there are limited clinical data and guidelines available to help guide physicians in formulating the next treatment steps in these patients. This review summarises currently available treatment options for patients with inhibitors, focussing on ITI regimens and those ITI strategies that may be used in difficult-to-treat patients. Some alternative, non-ITI approaches for inhibitor management, are also proposed.

• Authors: Rolf Ljung, Guenter Auerswald, Gary Benson, Gerry Dolan, Anne Duffy, Cedric Hermans, Victor Jiménez-Yuste, Thierry Lambert, Massimo Morfini, Silva Zupančić-Šalek, Elena Santagostino
• Journal: European journal of haematology (Eur J Haematol) Vol. 102 Issue 2 Pg. 111-122 (Feb 2019) ISSN: 1600-0609 [Electronic] England
• PMID: 30411401 (Publication Type: Journal Article, Review)
• Copyright: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Blood Coagulation Factor Inhibitors
• Isoantibodies
• F8 protein, human
• Factor VIII
• Factor IX

Topics

• Blood Coagulation Factor Inhibitors (blood, immunology)
• Desensitization, Immunologic
• Disease Management
• Drug Resistance
• Factor IX (adverse effects, therapeutic use)
• Factor VIII (adverse effects, therapeutic use)
• Hemophilia A (blood, complications, immunology, therapy)
• Hemophilia B (blood, complications, immunology, therapy)
• Hemorrhage (diagnosis, etiology, prevention & control, therapy)
• Humans
• Immune Tolerance
• Isoantibodies (blood, immunology)
• Premedication (methods)
• Treatment Outcome