Incidence of factor VIII inhibitors in severe haemophilia: the importance of patient age


Dr José Ignacio Lorenzo, Unidad de Coagulopatias Congénitas, Hospital ‘La Fe’, Avda. Campanar, 21, 46009 Valencia, Spain. E-mail:


The potential effect of age at the start of replacement therapy on the development of factor VIII (FVIII) inhibitors was assessed in 62 severe (FVIII < 2 IU/dl) haemophilia A patients who started FVIII therapy at one of two haemophilia centres. Inhibitors were tested on an annual basis. Persistent or high-titre inhibitors were detected in 15 patients (24%). Kaplan–Meier cumulative incidence at 3 years from first FVIII exposure was 41% (95% CI 22–67%) in patients starting therapy before the age of 6 months, 29% (95% CI 13–57%) in patients starting therapy between 6 and 12 months of age, and 12% (95% CI 4–34%) in those starting therapy beyond 1 year of age (P = 0·03). By multivariate analysis, the influence of age was shown to be independent of other variables, including calendar year at the onset of therapy and baseline FVIII plasma levels. In conclusion, patient age at initial treatment appears to influence inhibitor formation. If confirmed, this finding would have a major impact on the management of haemophilia.