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

M. de Kovel¹, C. Königs², S. Ranta³, C. Escuriola Ettingshausen⁴, K. Fischer⁵

¹PedNet Haemophilia Research Foundation, Utrecht, Utrecht, Netherlands, ²University Hospital Frankfurt, Goethe University, Frankfurt, Hessen, Germany, ³Department of Women's and Children's Health, Karolinska Univeristy Hospital and Karolinska Institute, Stockholm, Stockholms Lan, Sweden, ⁴Hämophilie Zentrum Rhein Main (HZRM), Mörfelden-Walldorf, Germany, Moerfelden-Walldorf, Hessen, Germany, ⁵University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands, Utrecht, Utrecht, Netherlands

Abstract Number: PB0181

Meeting: ISTH 2022 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Basic

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.

Table

Annualized -joint- bleeding rate according to baseline factor level activity

Image

Age -in years- at first joint bleed, according to FVIII level activity

To cite this abstract in AMA style:

de Kovel M, Königs C, Ranta S, Escuriola Ettingshausen C, Fischer K. Bleeding according to FVIII activity in 641 children with non-severe haemophilia – data from the PedNet study group [abstract]. https://abstracts.isth.org/abstract/bleeding-according-to-fviii-activity-in-641-children-with-non-severe-haemophilia-data-from-the-pednet-study-group/. Accessed September 24, 2023.

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