title: 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 treatment-years 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 HIV-seropositive 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.
authors.affiliation: Manchester University Department of Haematology, Manchester Royal Infirmary, Manchester, UK. Charles.Hay@cmft.nhs.uk
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Hay
authors.forename: Ben
authors.initials: B
authors.lastname: Palmer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chalmers
authors.forename: Ri
authors.initials: R
authors.lastname: Liesner
authors.forename: Rhona
authors.initials: R
authors.lastname: Maclean
authors.forename: Savita
authors.initials: S
authors.lastname: Rangarajan
authors.forename: Michael
authors.initials: M
authors.lastname: Williams
authors.forename: Peter W
authors.initials: PW
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005169:Factor VIII / Q000037:antagonists & inhibitors*; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000453:epidemiology / Q000628:therapy; D006467:Hemophilia A / Q000097:blood* / Q000453:epidemiology / Q000628:therapy; D006801:Humans; D015994:Incidence; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D006113:United Kingdom
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII