Evaluation of thrombin generation and emicizumab concentration in a cohort of severe Hemophilia A patients with and without inhibitor during emicizumab prophylaxis

M. Mormile¹, F. Barone², E. Baldacci¹, A. Ferretti², M. Chavez Orellana², G. Maestrini², A. Serrao³, F. Viola², A. Chistolini², C. Santoro¹

¹Hematology, University Hospital Policlinico Umberto I, Rome, Rome, Lazio, Italy, ²Hematology, Sapienza University of Rome, Rome, Lazio, Italy, ³Hematology, Sapienza University, Rome, Italy, Rome, Lazio, Italy

Abstract Number: PB0224

Meeting: ISTH 2022 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Novel Biotherapeutics in Hemophilia

Background: Although emicizumab is administered at fixed dose, its measurement could be occasionally required. Thrombin generation assay (TGA) can be used to monitor the global hemostatic response in emicizumab treated patients.

Aims: To measure emicizumab plasma levels and TGA in severe hemophilia A (HA) patients without and with inhibitors.

Methods: A modified one-stage FVIII clotting assay has been used to measure emicizumab concentration. The assay is calibrated against emicizumab using a dedicated plasma emicizumab calibrator and two levels of control. Thrombin generation was determined by Calibrated Automated Thrombography (CAT) using PPP-Reagent (phospholipids [4 uM], TF [5 pM]).

Results: 10 patients (non-inhibitor 6; inhibitor 4) received emicizumab. At start, 6 were without and 4 with inhibitor. No spontaneous bleedings occurred. Two patients experienced traumatic bleedings. One was treated with rFVIII concentrate (14th dose of life) and subsequently developed a high titer inhibitor. At the time of blood drawn he was considered an inhibitor patient. Emicizumab plasma levels increase during loading phase; median concentration at steady state is 42.2µg/mL (25.3-75). Lag time is in normal range after the first dose; ETP is variable among patients, almost always below normal range, and does not significantly differ between loading and steady state phase (table 1).

Comparing non inhibitor and inhibitor patients (table 2), at steady state median emicizumab concentration is 58.4 µg/mL (46.1-70.7) and 34.7 µg/mL (25.3-75), respectively.

In non-inhibitor patients, median ETP and peak are higher than in inhibitor patients: ETP 1073.14 nMxmin (562.17-1412.23), peak 92.67 nM (38.43-107.11) versus ETP 688.64 nMxmin (369.64-895.24), peak 43.065 nM (22.99-56.66).

Conclusion(s): We observed variability among patients as regards emicizumab concentration and TGA, but the drug was efficacious in all. It has to be explored if variables such as inhibitors, BMI, patients age, adherence to treatment, time period from the last infusion, influences emicizumab concentration and/or TGA.

Table 1

Emicizumab plasma levels and TEG parameters reported according to loading dose and steady state phase.

Table 2

Emicizumab plasma levels and TEG parameters reported for non-inhibitor and inhibitor patients

To cite this abstract in AMA style:

Mormile M, Barone F, Baldacci E, Ferretti A, Chavez Orellana M, Maestrini G, Serrao A, Viola F, Chistolini A, Santoro C. Evaluation of thrombin generation and emicizumab concentration in a cohort of severe Hemophilia A patients with and without inhibitor during emicizumab prophylaxis [abstract]. https://abstracts.isth.org/abstract/evaluation-of-thrombin-generation-and-emicizumab-concentration-in-a-cohort-of-severe-hemophilia-a-patients-with-and-without-inhibitor-during-emicizumab-prophylaxis/. Accessed September 24, 2023.

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