PB0648 - Mitigating the risk of bleeds and the risk for inhibitor formation when treating previously untreated patients (PUPs) with severe haemophilia A – a single-centre approach

Background: The ideal treatment of newly diagnosed severe haemophilia A patients avoids the consequences of bleeds while preserving the tolerance towards factor VIII (FVIII). We report our experience with an individualized approach to managing PUPs at a single haemophilia treatment center in Germany.

Aims: A possible methods to prevent inhibitors against factor VIII.

Methods: PUPs with severe haemophilia A (FVIII:C < 1%) treated at our centre in Duisburg, Germany, between January 2013 and August 2022 were followed prospectively. Our treatment approach includes early prophylactic physiotherapy and treatment with a plasma derived FVIII (pdFVIII/VWF) for at least the first 50 exposure days (EDs) while avoiding peak treatment moments. Non-urgent surgical procedures were postponed within the first 100 EDs. Ultrasound was performed every 3–6 months to check for joint status. Inhibitor levels were measured using the modified Bethesda assay every 3–4 EDs until ED 100, and every 3 months thereafter for 2 years for all patients.

Results: 36 of 39 PUPs had started treatment. At the time of data cut-off, 29 patients had over 50 EDs to FVIII, 7 patients had more than 20 EDs. 27 patients had started prophylaxis within the first 10 EDs. The initial schedule ranged from 21 IU/kg every 10 days up to 40 IU/kg twice per week. Only 3 spontaneous bleeds required treatment; 33 patients (92%) remained free of treated spontaneous bleeds during prophylaxis. 1 of 36 had developed an inhibitor after the 4th exposure day (2.6 %). Of the 9 patients treated conventionally before 2013, 9 (44%) patients had developed an inhibitor. Ultrasound and MRI assessment showed no sign of joint modification.

Conclusion(s): With no joint modifications detected so far and 1 inhibitor development in 36 patients, we are confident in further applying the treatment concept described.