Summary

Findings from a recent study suggest that earlier start oftreatment with factor VIII in patients with severe hemophilia isassociated with a higher risk to develop inhibitors.We set out to assess the association between age of firstadministration of clotting factor VIII and the risk to developinhibitors in infants with severe hemophilia A.This work was a cohort study, carried out in the nationalhemophilia treatment center. The study included eighty-oneconsecutive patients with severe hemophilia A who receivedtheir first dose of factor VIII between 1975 and 1998. Patientswere followed until their last visit in 2001 or 2002.The average follow-up was 16 years (range 3-26). Persistentinhibitory antibodies developed in 12 of 81 patients (15%). Cumulative incidence at 100 exposure days was 34% (95%confidence interval 7-61%) in patients starting therapy beforethe age of 6 months, 20% (4-36%) in patients starting therapybetween 6 months and 1 year, 13% (0-27%) in those startingtherapy between 1 and 1.5 years, and 0% in those who startedtherapy beyond 1.5 years of age (p for trend 0.03).Our findings confirm that age of first factor VIII administrationin children with severe hemophilia A is inversely associated withthe risk to develop antibodies against factor VIII. The role ofconfounding factors such as the type of factor VIII mutation andenvironmental factors needs to be evaluated.