title: Risk of inhibitor development in mild haemophilia A increases with age.
abstract: Mild haemophilia A is a rare disease with a relatively mild phenotype. Treatment with factor VIII (FVIII) is indicated after trauma or for surgery only. FVIII infusion may result in the development of inhibiting antibodies against FVIII. This study describes the relation between age and other risk factors for inhibitor development in mild haemophilia. A retrospective cohort study was conducted among all patients with mild haemophilia (FVIII 0.05-0.40 IU mL(-1)) registered at the van Creveldkliniek, University Medical Centre Utrecht, The Netherlands. Data on peak treatment with FVIII, gene mutation and history of inhibitor development were obtained from patient files from the period between 1st January 1970 and 31st December 2009. A total of 231 out of 297 (78%) patients had at least one exposure to FVIII, of whom 14 (6.1%) developed an inhibitor to FVIII at a median age of 66 years after a median of 50 exposure days (ED). Age at first exposure, age at peak treatment, number of peak treatments and Arg593Cys mutation were significantly associated with the development of an inhibitor, while continuous infusion with FVIII was not. Although the incidence of inhibitors in mild haemophilia is low, it increases with age and peak treatments. With increasing age patients with mild haemophilia will suffer from co-morbidity more frequently, requiring surgical interventions and exposing them to an increased risk of inhibitor development. Especially patients with a change of arginine in cysteine at 593 are at risk for inhibitor development.
authors.affiliation: Van Creveldkliniek, Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands. E.Mauserbunschoten@umcutrecht.nl
authors.forename: E P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.forename: I E M
authors.initials: IE
authors.lastname: Den Uijl
authors.forename: R E G
authors.initials: RE
authors.lastname: Schutgens
authors.forename: G
authors.initials: G
authors.lastname: Roosendaal
authors.forename: K
authors.initials: K
authors.lastname: Fischer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005169:Factor VIII / Q000008:administration & dosage / Q000235:genetics; D006467:Hemophilia A / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII