The Role of Age at First Exposure and Therapy Regimen on the Development of Neutralizing FVIII Antibodies in Hemophilia A.

In order to assess the impact of age at first exposure to F VIII and therapy regimen on neutralizing FVIII-antibodies in previously untreated patients (PUP) with hemophilia A a prospective study was performed.

Over a 23-years study period a total of 74 severely affected hemophilia A -PUPs have been consecutively recruited, treated with F VIII and investigated for inhibitor development. The patients were divided into two groups according to their treatment regimen: Group 1 (n=23) started prophylaxis at the age of 1 year (before or immediately after the first relevant bleed). Group 2 (n=43) was treated on-demand or prophylaxis was started after more than 2 bleeds. The following parameters were equally distributed among both groups: caucasian ethnicity, intron-22-inversion, age at 1^st ED >0.5 years.

Out of 74 hemophilia A patients 23 developed inhibitors (31%). Inhibitor incidence was 0% (1 transient inhibitor out of 23 patients) in those patients who received early prophylaxis (group 1) and 42% (18/43 patients) in case of delayed prophylaxis or on-demand treatment (group 2) (p=0.002).

No linear correlation was found between the age at first exposure and inhibitor formation. However, patients treated before the age of 0.5 years showed a significantly higher inhibitor incidence (62%) than those treated at an more advanced age. Our data confirm that very early age at first exposure is a risk factor for inhibitor development in severe hemophilia A patients. Early prophylaxis might be protective against inhibitor development. To confirm the data a larger patient cohort has to be investigated.