Semin Thromb Hemost 2006; 32: 015-021
DOI: 10.1055/s-2006-946910
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Current and Future Approaches to Inhibitor Management and Aversion

Charles Hay1 , Michael Recht2 , Manuel Carcao3 , Birgit Reipert4
  • 1Manchester Royal Infirmary, Manchester, United Kingdom
  • 2Phoenix Children's Hospital, Phoenix, Arizona
  • 3Hospital for Sick Children, Toronto, Ontario, Canada
  • 4Baxter BioScience, Vienna, Austria
Further Information

Publication History

Publication Date:
21 November 2006 (online)


Immune tolerance induction (ITI) is the most common approach used to eliminate inhibitors that develop in hemophilia A patients following exposure to factor (F) VIII therapy. ITI generally requires ongoing long-term exposure to factor replacement therapy using FVIII or FIX. Although plasma-derived products have been the mainstay of ITI therapy in the past, recent data indicate that high-purity (i.e., recombinant) rFVIII products are probably equally effective. For patients who have failed to respond to ITI treatment, or for those at high risk to do so, immunosuppressive therapy may be helpful. Rituximab has demonstrated a possible clinical benefit in hemophilic and nonhemophilic patients developing FVIII inhibitors, but benefit in those with congenital hemophilia and inhibitors has not been established and more extensive clinical studies are needed. More recently, research on reducing the incidence of inhibitor development has included mutagenizing key epitopes of the FVIII antigenic molecule to alter its immunogenicity without affecting biological activity, as well as induction of tolerance by gene therapy with immunodominant A2 and C2 domains of FVIII presented by B cells as immunoglobulin fusion proteins.


Charles HayM.D. 

Clinical Manager, Department of Clinical Haematology, Manchester Royal Infirmary

Oxford Road, Manchester M13 9WL United Kingdom