Semin Thromb Hemost 2006; 32: 010-014
DOI: 10.1055/s-2006-946909
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Inhibitor Development in Hemophiliacs: The Roles of Genetic versus Environmental Factors

Christine A. Lee1 , David Lillicrap2 , Jan Astermark3
  • 1Haemophilia Centre & Haemostasis Unit, Royal Free & University College Medical School, UCL, London, United Kingdom
  • 2Department of Pathology and Molecular Medicine, Richardson Laboratory, Queen's University, Kingston, Ontario, Canada
  • 3Department for Coagulation Disorders, Malmö University Hospital, Malmö, Sweden
Further Information

Publication History

Publication Date:
21 November 2006 (online)


Approximately 5 to 7% of patients with hemophilia A have inhibitory antibodies to factor (F) VIII, which increases to ~13% in patients with severe disease. The strongest determinant of the risk of inhibitor development identified is the type of mutation in the FVIII gene that gives rise to the disease. However, accumulating evidence clearly indicates that other genetic factors (e.g., major histocompatibility complex alleles and other immune-modulatory genes) and factors associated with treatment (e.g., type of FVIII concentrate, route of administration, and age of first exposure) may also influence the risk of inhibitor development. There is much interest in identifying such genetic and treatment-related factors to help minimize the risk of inhibitor development and improve treatment outcomes.


Christine A LeeM.D. 

Royal Free & University College Medical School, UCL, London

UK, Haemophilia Centre & Haemostasis Unit, London NW3 2QG United Kingdom