15. Prediction of Inhibitors in Severe Hemophilia

  1. Emérito-Carlos Rodríguez-Merchán MD, PHD3,4 and
  2. Leonard A. Valentino MD5
  1. H. Marijke van den Berg MD, PhD1,2 and
  2. Kathelijn Fischer MD, PhD2

Published Online: 12 MAY 2011

DOI: 10.1002/9781119979401.ch15

Current and Future Issues in Hemophilia Care

Current and Future Issues in Hemophilia Care

How to Cite

van den Berg, H. M. and Fischer, K. (2011) Prediction of Inhibitors in Severe Hemophilia, 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.ch15

Editor Information

  1. 3

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

  2. 4

    School of Medicine, Autonomous University, Madrid, Spain

  3. 5

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

Author Information

  1. 1

    Meander Hospital, Amersfoort, The Netherlands

  2. 2

    University Medical Center Utrecht, The Netherlands

Publication History

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

ISBN Information

Print ISBN: 9780470670576

Online ISBN: 9781119979401



  • inhibitors;
  • severe hemophilia A;
  • risk score;
  • genetic;
  • risk factors;
  • non-genetic risk factors


Inhibitor development still is the most serious side effect of modern hemophilia treatment. It has been discovered recently that not only genetic factors, but also non-genetic factors can induce the development of inhibitors. Moreover, the recognition that intensive treatment at the start of treatment with factor VIII is a high-risk factor for inhibitor development has defined a clear clinical decision point. We developed a risk score for patients with severe hemophilia A at the time of first treatment, including positive family history (2 points), high-risk factor VIII gene mutations (2 points), and intensive initial treatment (3 points). The score can differentiate between low risk (0 points; 6% inhibitor development) and high risk (>2 points; 57% inhibitor development).

To investigate the acceptance of the risk score in clinical practice a survey was performed. All hematologists agreed that major gene defects, family history of inhibitors and ethnicity were positively associated with inhibitor development. Early intensive treatment was considered the most important exogenous risk factor, whereas early onset of prophylaxis and avoidance of early surgery were considered likely to reduce inhibitor development.