Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom

Abstract

The age-adjusted incidence of new factor VIII inhibitors was analyzed in all United Kingdom patients with severe hemophilia A between 1990 and 2009. Three hundred fifteen new inhibitors were reported to the National Hemophilia Database in 2528 patients with severe hemophilia who were followed up for a median (interquartile range) of 12 (4-19) years. One hundred sixty (51%) of these arose in patients ≥ 5 years of age after a median (interquartile range) of 6 (4-11) years' follow-up. The incidence of new inhibitors was 64.29 per 1000 treatment-years in patients< 5 years of age and 5.31 per 1000 treatment-years at age 10-49 years, rising significantly (P = . 01) to 10.49 per 1000 treatmentyears in patients more than 60 years of age. Factor VIII inhibitors arise in patients with hemophilia A throughout life with a bimodal risk, being greatest in early childhood and in old age. HIV was associated with significantly fewer new inhibitors. The inhibitor incidence rate ratio in HIVseropositive patients was 0.32 times that observed in HIV-seronegative patients (P < . 001). Further study is required to explore the natural history of later-onset factor VIII inhibitors and to investigate other potential risk factors for inhibitor development in previously treated patients. © 2011 by The American Society of Hematology.