PB0181 - Bleeding according to FVIII activity in 641 children with non-severe haemophilia - data from the PedNet study group

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

MD

Marloes De Kovel, MSc

Epidemiologist and Research Coordinator at PedNet
PedNet Haemophilia Research Foundation, Baarn, the Netherlands.
Baarn, Drenthe, Netherlands

Co-Author(s)

Königs Christoph, Dr. Dr.

Physician
Goethe University Frankfurt, University Hospital, Department of Pediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Frankfurt am Main, Germany
Frankfurt, Hessen, Germany
SR

Susanna Ranta

Physician
Dep. of Pediatrics, Clinic of Coag. Disorders Karolinska Hospital
Stockholm, Sodermanlands Lan, Sweden
Carmen Escuriola-Ettingshausen, MD

Physician
Haemophilia Centre Rhine-Main, Mörfelden-Walldorf, Germany
Mörfelden-Walldorf, Hessen, Germany
KF

Kathelijn Fischer, MD, PhD

Pediatric Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands

Background: Novel therapies, including modified replacement therapy and gene therapy, provide opportunity to substantially increase baseline FVIII activity levels, or (partially) correct haemostasis. Information on bleeding phenotype in non-severe haemophilia provides the best possible information regarding optimum target for prophylactic treatment.

Aims: To assess bleeding according to baseline FVIII activity in children with non-severe haemophilia A (HA).

Methods: HA patients in the PedNet Registry (Clin.gov.trial NCT02979119) by January 1st, 2020 with baseline factor FVIII activity between 1%-25% (0.01 UI/mL to 0.25 UI/mL) were included. Patients were followed from diagnosis to: January 1st, 2020, 18 years of age, start prophylaxis, or inhibitor diagnosis. Onset of bleeding and annual (joint) bleeding rate (ABR/A(J)BR) were compared according to categories of baseline FVIII level: 1-2%, 3-5%, 6-10%, 11-15%, 16-20% and 21-25%. ABR and A(J)BR were established by negative binomial modelling. Onset of bleeding was analysed using Kaplan-Meier survival.

Results: 641 non-severe HA patients were included and were followed until a median age of 9.7 (IQR 6.0-13.8) years and for 5249 patients years in total.
Median age at first joint bleed was higher with increasing FVIII activity: from 1.4 (for 1-2%), to 2.0 (for 3-5%), to 4.8 (for 6-10%), and 12.6 years for patients with 16-20% FVIII (Figure 1).
Overall ABR was low, with 0.3 for all bleeds and 0.1 for joint bleeds (AJBR). A(J)BRs decreased with increasing baseline FVIII activity (Table 1), ABR from 1.6 (for 1-2%) to 0.1 for patients with 16-25% FVIII, AJBR was 0.5 for 1-2% and approached zero in patients with FVIII levels >6%.

Conclusion(s): Children with non-severe HA have a low bleeding tendency. Onset of (joint) bleeding was delayed and bleeding decreased with increasing FVIII levels. In A(J)BR a steep decrease is observed in patients with FVIII activities >2%. Bleeding rates approached zero at 16% for all bleeds, and at 6% for joint bleeds.