Molecular Mechanisms of Inhibitor Development in Hemophilia

Authors: Tieu, P., Chan, A., and Matino, D.

Mediterranean Journal of Hematology and Infectious Diseases 2020

Affiliations: McMaster Univ, McMaster Childrens Hosp, Dept Pediat, Hamilton, ON, Canada

Abstract: The 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 further investigation.