PB1326 - Real-world data on correlation between emicizumab plasma levels, ex-vivo procoagulant profile and spontaneous joint annualized bleeding rate of patients on emicizumab prophylaxis

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

Francisco José López Jaime, MD

Hematologist
Hemostasis and Thrombosis Unit, Regional University Hospital of Málaga, IBIMA, Málaga, Spain.
Málaga, Andalucia, Spain
AM

Ana Marco

Hematologist
University General Hospital Dr. Balmis, Alicante, Spain
Alicante, Comunidad Valenciana, Spain
AM

Adrián Montaño, PhD (he/him/his)

Postdoctoral researcher
Hemostasis and Thrombosis Unit, Regional University Hospital of Málaga / University of Salamanca
Málaga, Andalucia, Spain
�P

Ángeles Palomo Bravo

Hematologist
Hematology Service, Hospital Materno-Infantil de Málaga, Málaga, Spain.
Malaga, Andalucia, Spain
FM

Francisco D. Muñoz López

Hematologist
Hematology Service, Hospital Materno-Infantil de Málaga, Málaga, Spain.
Malaga, Andalucia, Spain
PM

Pascual Marco

Hematologist
Department of Clinical Medicine, Universidad Miguel Hernández, Alicante, Spain
Alicante, Comunidad Valenciana, Spain

Presenting Author(s)

Ihosvany Fernández-Bello, PhD (he/him/his)

Postdoctoral Researcher
Hemostasis and Thrombosis Unit, Regional University Hospital of Málaga, IBIMA, Málaga, Spain.
Málaga, Andalucia, Spain

Background: Real-world data on correlation between emicizumab plasma levels, ex-vivo procoagulant profile and spontaneous joint annualized bleeding rate (SJABR) of severe hemophilia patients on emicizumab are scarce

Aims: Evaluation of correlation between emicizumab plasma levels, ex-vivo procoagulant profile and SJABR in a cohort of patients on emicizumab treatment

Methods: Whole blood of subjects on emicizumab steady state was drawn immediately before infusion of the emicizumab prophylactic dose. Emicizumab plasma levels was evaluated by the aPTT modified test (Stago). Number of spontaneous joint bleedings (SJB) were retrospectively recorded from the patients’ clinical history. Ex-vivo procoagulant profile of patients was evaluated by thrombin generation test (TGT, Genesia, Stago) and rotational thromboelastometry (ROTEM, naTEM test, Werfen).

Results: A total of 19 patients with a median (25th-75th percentiles) [minimum-maximum] age of 15.2 (6.7-28.5) [2.2-47.9] years old were analyzed. Despite the high variability in plasma levels of emicizumab: 44.0 (38.0-51.0) [27.2-69.2] mcg/mL, none of the patients presented SJB along the follow-up period of 46.0 (26.0-78.9) [3-225] weeks. No correlation between emicizumab plasma levels and TGT or ROTEM were detected. We observed lower thrombin generation in patients compared to controls, though, by the contrary, ROTEM showed similar or even shorter time for clot formation than healthy subjects (Table 1).

Conclusion(s): Emicizumab provide excellent protection of patients from SJB. Plasma levels of emicizumab may be quite variable between patients but this fact does not impact negatively on the development of SJB. Ex-vivo global procoagulant profile of subjects do not correlate with the plasma levels of emicizumab. TGT and ROTEM showed contradictory results describing lower thrombin generation capacity compared to healthy controls in TGT but similar or even higher procoagulant function in patients by ROTEM. Further studies are needed to explain these findings and their clinical significance.