Abstract Number: PB0066
Meeting: ISTH 2021 Congress
Background: Emicizumab, a non-factor therapy for hemophilia A (HA) treatment, may require concomitant pro-hemostatic therapies to fully protect patients against breakthrough bleedings. Further, HA patients with inhibitors treated with emicizumab may also require FVIII for immune tolerance induction (ITI). Previously, we demonstrated in vitro that the combination of emicizumab, plasma-derived factor VIII concentrate containing von Willebrand factor (pdFVIII/VWF), and rFVIIa did not trigger a multiplying effect on thrombin generation (TG). Since several pdFVIII/VWF concentrates with different purification and production processes are available, further studies are needed.
Aims: To assess the TG profiles of another pdFVIII/VWF concentrate, Anti-Hemophilic Factor (AHF) (Koate, Grifols) in combination with emicizumab and rFVIIa, in a simulated in vitro model of ITI with bleeds.
Methods: Pooled HA plasma with inhibitors (HAp-i, Technoclone) (19 BU), containing emicizumab (50 μg/mL) plus AHF (1 to 4.5 IU/mL) was combined with rFVIIa (0.9 and 7 μg/mL). Samples were analyzed using a Calibrated Automated Thrombogram (CAT) assay and PPP Reagent Low (Stago). TG reaction parameters were calculated using CAT software.
Results: Thrombin peak (TP) range of normal plasma was established based on 13 healthy individual plasma samples (TP: 47-104 nM). In HAp-i with emicizumab 50 mg/mL, TP levels were below normal ranges. Addition of high concentration of AHF (4.5 IU/mL) to HAp-i with emicizumab slightly increased TP compared to HAp-i without emicizumab (TP:47 and 34 nM, respectively), reaching the lowest level of TP normal range. When rFVIIa was added, the triple combination did not trigger a multiplying effect on TP but an additive increase comparable to normal plasma TP ranges, even at high concentrations of AHF (TP: 74 and 138 nM, for 0.9 and 7 μg/mL rFVIIa, respectively).
Conclusions: In agreement with previous data with a similar pdFVIII/VWF, the combination of emicizumab plus AHF and rFVIIa did not trigger a multiplying, but an additive effect on TG.
To cite this abstract in AMA style:Bravo M-, Raventos A, Perez A, Costa M, Willis T. Non-thrombogenic Effect Observed with Simulated Concomitant Administration of Anti-hemophilic Factor, Emicizumab and rFVIIa on Thrombin Generation [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/non-thrombogenic-effect-observed-with-simulated-concomitant-administration-of-anti-hemophilic-factor-emicizumab-and-rfviia-on-thrombin-generation/. Accessed December 5, 2021.
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