Inhibitors and prophylaxis in paediatric haemophilia patients: Focus on the German experience

Prophylaxis is now an established treatment standard in haemophilia in Western Europe and the US with multiple studies demonstrating the clinical benefits of prophylaxis over on-demand treatment. In Western Europe in particular, prophylactic use of factor VIII (FVIII) is high as a result of the findings from the early prophylaxis studies and adherence to national guidelines. Unfortunately, prophylaxis has not yet been implemented on a worldwide basis. The introduction of prophylaxis by haemophilia treatment centres in Bremen, Frankfurt and Munich, as recommended in German guidelines, has significantly improved outcomes for our young haemophilia patients. In the Frankfurt centre, a decreasing rate of inhibitors has been observed since prophylaxis was started early, dosing was individualized, and the importance of treatment continuity was recognized. The centres in Munich and Bremen have explored the possibility of further reducing inhibitor rates using early tolerization – a new prophylaxis regimen that introduces low FVIII doses administered once weekly as soon as a bleeding tendency is observed – with excellent results. All three centres avert the induction of immunological danger signals by avoiding the use of central venous catheters, postponing vaccination wherever possible and not undertaking elective surgery during the early FVIII exposure days. The benefits of using this approach have been confirmed by the remarkably low rates of inhibitors in previously untreated patients reported at these centres. Hopefully, as we and others explore new prophylaxis regimens for our paediatric patients, we can work towards the goal of one day overcoming this serious complication of haemophilia treatment.