PB0224 - Evaluation of thrombin generation and emicizumab concentration in a cohort of severe Hemophilia A patients with and without inhibitor during emicizumab prophylaxis

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

MM

Maria Rosaria Mormile

Biologist
Hematology, University Hospital Policlinico Umberto I, Rome
Rome, Lazio, Italy
FB

Francesco Barone

Biologist
Hematology, Sapienza University of Rome
Rome, Lazio, Italy
EB

Erminia Baldacci

Hematologist
Hematology, University Hospital Policlinico Umberto I, Rome
Rome, Lazio, Italy
AF

Antonietta Ferretti

Hematologist
Hematology, Sapienza University of Rome
Rome, Lazio, Italy
MC

Maria Gabriela Chavez Orellana

MD
Hematology, Sapienza University of Rome
Rome, Lazio, Italy
GM

Giacomo Maestrini

Hematologist
Hematology, Sapienza University of Rome
Rome, Lazio, Italy
AS

Alessandra Serrao, MD

MD
Hematology, Sapienza University, Rome, Italy
Rome, Lazio, Italy
FV

Federica Viola

Hematologist
Hematology, Sapienza University of Rome
Rome, Lazio, Italy
AC

Antonio Chistolini

Director
Dipartimento di Medicina Traslazionale e di Precisione Sapienza Università di Roma
Roma, Lazio, Italy

Presenting Author(s)

CS

Cristina Santoro

Medical Doctor
Ematologia, Azienda Ospedaliera Universitaria Policlinico Umberto I, Roma
Rome, Lazio, Italy

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.