1 Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
2 Department of Pediatrics, McMaster Children’s Hospital, McMaster University, Hamilton, Ontario, Canada.
3 Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
4 Department of Medicine, McMaster Children’s Hospital, McMaster University, Hamilton, Ontario, Canada.
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development of neutralizing antibodies in hemophilia is a serious
complication of factor replacement therapy. These antibodies, also
known as “inhibitors”, significantly increase morbidity within the
hemophilia population and lower the quality of life for these patients.
People with severe hemophilia A have an overall 25-40% lifetime risk of
inhibitor development, compared to that of 5-15% lifetime risk in those
with moderate/mild hemophilia A. The risk is lower in hemophilia B
population (about 1-5%) and occurrence of inhibitors is almost only
seen in patients with severe hemophilia B. The understanding of the pathophysiological
mechanism leading to the development of inhibitors in patients with
hemophilia has improved considerably over the last 2 decades.
Identification of early biomarkers which predict inhibitor development
in previously untreated patients with hemophilia will assist in risk
identification and possible early intervention strategies. In this
review, we aim to summarize the molecular mechanisms of inhibitor
development in hemophilia and to identify potential areas in need of
Primary Immune Response
|Figure 1. Primary immune response in hemophilia inhibitor development. APC: antigen- presenting cells; MMR: mannose receptor; LRP: lipoprotein receptor-related protein; TCR: T- cell receptor.|
Secondary Immune Response
Actors in Inhibitor Development
Factor IX Inhibitors