Skip to main content
ISTH 2023 Main banner
Back

    Poster Networking

    Hemophilia and Rare Bleeding Disorders

    Poster Networking Session

    PB0682 - In vitro Response to Bypassing Agents and Long Term Follow-up of Patients with Severe Hemophilia A on Prophylaxis with Emicizumab.

    Monday, June 26, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    Background: Bleeding in patients with severe hemophilia A (PwHAS) on prophylaxis with emicizumab is similar to that seen in patients with mild-moderate HA. Therefore patients will require administration of FVIII concentrates (patients without inhibitor) or bypassing agents (patients with inhibitor) in case of acute bleeding or surgery. Thrombosis was reported in patients on emicizumab prophylaxis who received activated prothrombin complex concentrate (aPCC), limiting its use. Additionally, experiences in long-term administration of emicizumab are insufficient.

    Aims: 1) To compare the in vitro procoagulant effect of FVIII and bypass agents in PwHAS on prophylaxis with emicizumab; 2) To evaluate 3-years evolution of these PwHAS.

    Methods: Blood was collected with corn trypsin inhibitor (CTI).Thromboelastometry (ROTEM®) was triggered by 1:50,000 EXTEM and thrombin generation (TG) with PPP-Reagent LOW®. Spontaneous annualized bleeding rates (ABRs) were recorded. Data of the follow-up from 2020 to 2022 of 9 PwHAS without inhibitor were collected.

    Results: Twenty-one PwHAS (8 with inhibitor), 41.5±14.5 years old; and 20 healthy controls were included.
    In-vitro addition of rFVIIa (1μg/ml) or rFVIII (100 IU/dl) nearly normalized coagulation. A concentration of aPCC equivalent to what would be obtained after one dose of 2.5 IU/kg was able to normalize procoagulant functions with a similar effect than that would be obtained after one single dose of 90 μg/kg rFVIIa (Figure 1). ABR (zero in 60% of PwHAS) , clotting time (CT) and Peak of TG in these patients was stable along 3 years of follow-up. Interindividual differences in CT and Peak were observed, that no correlated with ABR (Table 1).

    Conclusion(s): Long term prophylaxis with emicizumab protects PwHAS from bleeding. Adequate dosis of rFVIII and bypass agents could be used in PwHAS treated with emicizumab. Lack of correlation of ABR with CT and Peak indicated the necessity of further studies to determine the most sensitive global test conditions.