13. Epidemiology of Inhibitors

  1. Emérito-Carlos Rodríguez-Merchán MD, PHD2,3 and
  2. Leonard A. Valentino MD4
  1. Johanna G. van der Bom MD, PhD

Published Online: 12 MAY 2011

DOI: 10.1002/9781119979401.ch13

Current and Future Issues in Hemophilia Care

Current and Future Issues in Hemophilia Care

How to Cite

van der Bom, J. G. (2011) Epidemiology of Inhibitors, in Current and Future Issues in Hemophilia Care (eds E.-C. Rodríguez-Merchán and L. A. Valentino), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781119979401.ch13

Editor Information

  1. 2

    Department of Orthopedic Surgery and Hemophilia Unit, La Paz University Hospital, Spain

  2. 3

    School of Medicine, Autonomous University, Madrid, Spain

  3. 4

    Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL, USA

Author Information

  1. Leiden University Medical Center, Leiden, The Netherlands

Publication History

  1. Published Online: 12 MAY 2011
  2. Published Print: 13 MAY 2011

ISBN Information

Print ISBN: 9780470670576

Online ISBN: 9781119979401



  • etiology;
  • causes;
  • risk factors;
  • methods;
  • methodology;
  • incidence;
  • rate;
  • occurrence;
  • confounding;
  • selection bias;
  • study design


During the first decade of the 21st century, knowledge about the etiology of inhibitors has advanced rapidly with the discovery of several factors that contribute to the incidence of inhibitors, particularly the role of treatment related factors. The most intriguing observations are those that suggest that avoiding endogenous “danger signals” early during the replacement treatment of patients with hemophilia A reduces their risk to develop inhibitors. If true, it might be possible to prevent inhibitors in a significant number of patients. Knowledge about the etiology of inhibitors comes from both basic science studies and epidemiological studies. Epidemiological studies compare inhibitor incidences between patients with or without potential risk factors. Confounding and selection bias may be alternative explanations for observed differences. This chapter describes how epidemiological studies have advanced our knowledge of risk factors for inhibitor development in patients with hemophilia. It also discusses specific methodological issues to be considered when interpreting studies that relate inhibitor occurrence to potential risk factors for inhibitors.