Abstract Number: PB0566
Meeting: ISTH 2021 Congress
Background: Emicizumab prophylaxis substantially reduces bleeding episodes in patients with hemophilia A and factor (F)VIII inhibitor (PwHA-inh). The main therapeutic approach to eradicate FVIII inhibitor in PwHA is immune tolerance induction treatment (ITI). Concomitant therapy with ITI and emicizumab prophylaxis could provide additional benefits but remains to be investigated.
Aims: We have assessed coagulation potential in an in vitro simulated model of ITI for PwHA-inh and emicizumab.
Methods: FVIII-deficient plasma was incubated with anti-A2 and anti-C2 monoclonal antibodies (0, 1, and 10 BU/mL each). Emicizumab (50 µg/mL; therapeutic dose) was spiked in together with bypassing agents (BPAs): activated prothrombin complex concentrates (1.3 U/mL; corresponded to 50 IU/kg), recombinant FVIIa (2.2 µg/mL; 90 µg/kg), or plasma-derived FVIIa/FX (1.5 µg/mL; 60 µg/kg), and FVIII (100 and 200 IU/dL; 50 and 100 IU/kg, respectively). These samples were analyzed by mixed ellagic acid and tissue factor-triggered clot waveform analysis, and adjusted-|min1| (Ad|min1|) was calculated.
Results: Ad|min1| levels in FVIII-deficient high titre inhibitor plasmas (10 BU/mL) were increased in the presence of emicizumab with various concentrations of FVIII concomitant with each BPA, but remained within the normal range even under conditions of maximal coagulation potentials. Those in FVIII-deficient low titre inhibitor plasmas (1 BU/mL) together with BPA and FVIII (200 IU/dL) showed values near or beyond the normal range, but a half concentration of rFVIIa based on the half-life in blood showed within the normal range. In contrast, Ad|min1| values in non-inhibitor samples incorporating emicizumab, FVIII (100 and 200 IU/dL) and each BPA were far beyond the normal range, but the coagulation potential in co-presence of FVIII (100 IU/dl) and a half concentration of rFVIIa remained within the normal range.
Conclusions: The results may support the feasibility of concurrent ITI in emicizumab-treated PwHA-inh.
To cite this abstract in AMA style:Nakajima Y, Tonegawa H, Noguchi-Sasaki M, Nogami K. In vitro Analysis of Coagulation Function in Emicizumab-treated Hemophilia A Patients with Inhibitors under Immune Tolerance Induction Treatment [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/in-vitro-analysis-of-coagulation-function-in-emicizumab-treated-hemophilia-a-patients-with-inhibitors-under-immune-tolerance-induction-treatment/. Accessed September 16, 2021.
« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/in-vitro-analysis-of-coagulation-function-in-emicizumab-treated-hemophilia-a-patients-with-inhibitors-under-immune-tolerance-induction-treatment/