Abstract Number: PB0057
Meeting: ISTH 2021 Congress
Background: Hemophilia A (HA) patients under emicizumab prophylaxis treatment may require the concomitant use of procoagulant factors for breakthrough bleedings or immune tolerance induction. Previous in vitro studies demonstrated that the combination of emicizumab and plasma-derived Factor VIII/Von Willebrand Factor (pdFVIII/VWF) has a non-additive effect on thrombin generation (TG).
Aims: The aim of this study was to evaluate the ex vivo combination of emicizumab with a pdFVIII/VWF concentrate by rotational thromboelastometry (ROTEM).
Methods: Blood samples obtained from 12 adult patients with severe HA without inhibitors on prophylaxis with emicizumab were drawn in citrate plus corn trypsin inhibitor (CTI) tubes. Modified Tissue Factor (TF) activated ROTEM assay (EXTEM) was performed by using reagent diluted 1:100,000 (low concentration of TF). Clotting time (CT) and time to maximum clot formation velocity (MAXV-t) parameters were registered. In vitro spiking was performed with increasing concentrations of pdFVIII/VWF (10 to 400 IU/dL), recombinant activated factor VII (rFVIIa, 0.9 mg/mL) or activated prothrombin complex concentrate (aPCC, 0.5 U/mL).
Results: ROTEM showed that whole blood CT (Figure 1) and MAXV-t (Figure 2) of patients treated with emicizumab were longer than those from healthy controls, and addition of pdFVIII/VWF at 50 IU/dL (≡25 IU/kg) normalized these parameters. Increasing ex vivo concentrations of pdFVIII/VWF shortened CT and MAXV-t, with high concentrations of pdFVIII/VWF producing an enhanced procoagulant effect of emicizumab, similar to rFVIIa. The addition of aPCC resulted in a higher synergistic procoagulant profile, which was not reached with the highest concentration of pdFVIII/VWF (400 IU/dL).
Conclusions: ROTEM with CTI samples triggered by a low concentration of TF was a suitable method to evaluate the concomitant use of pdFVIII/VWF in patients on prophylaxis with emicizumab. These results showed that emicizumab plus pdFVIII/VWF combination did not trigger a multiplying effect on clot formation and were aligned with previous in vitro data using TG assay.
To cite this abstract in AMA style:Monzón Manzano E, Arias-Salgado E, Acuña P, Bravo M-, Raventos A, Perez A, Álvarez Román MT, Butta N, Costa M, Willis T, Jimenez-Yuste V. Ex vivo Evaluation of the Effect of Plasma-derived Factor VIII/von Willebrand Factor in Patients with Severe Hemophilia A on Prophylaxis with Emicizumab by ROTEM [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/ex-vivo-evaluation-of-the-effect-of-plasma-derived-factor-viii-von-willebrand-factor-in-patients-with-severe-hemophilia-a-on-prophylaxis-with-emicizumab-by-rotem/. Accessed October 19, 2021.
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