PB0172 - Results of thromboelastometry and thrombin generation assays for emicizumab prophylaxis monitoring

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

SA

Sara Arcudi, MD

Academic researcher, MD, PhD
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy

Co-Author(s)

MC

Marigrazia Clerici

BSc
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milano, Lombardia, Italy
ES

Erica Scalambrino

BSc
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milano, Lombardia, Italy
Roberta Gualtierotti, MD, PhD

Assistant Professor
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy
Cristina Novembrino, PhD

BSc
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy
AT

Addolorata Truma

MD
Università degli Studi di Milano, Department of Pathophysiology and Transplantation
Milano, Lombardia, Italy
AC

Alessandro Ciavarella

PhD Student
Università degli Studi di Milano, Department of Biomedical Sciences for Health
Milan, Lombardia, Italy
SS

Simona Maria Siboni

Hematologist
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milan, Lombardia, Italy
Eugenia Biguzzi, MD

Hematologist
Hematology clinic, Oncology Institute of Southern Switzerland, EOC
Bellinzona, Ticino, Switzerland
AT

Armando Tripodi

Professor
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia e Trhombosis Center, Milan, Italy
Milano, Lombardia, Italy
Flora Peyvandi, MD, PhD

Professor of Internal Medicine; Director of the Angelo Bianchi Bonomi Hemophilia & Thrombosis Center
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Milan, Lombardia, Italy

Background: The ability of coagulation assays to monitor severe hemophilia A (HA) patients on emicizumab prophylaxis has been poorly investigated.

Aims: To report the results of non-activated rotational thromboelastometry (NATEM), thrombin generation assay (TGA) and to correlate findings with plasma emicizumab concentration (EmiC).

Methods: Consecutive HA patients on emicizumab prophylaxis at steady state were enrolled in an observational prospective study. TGA was assessed with a homemade method upon addition to plasma of tissue-factor (1pM) and synthetic phospholipids (1µM). NATEM was measured for whole blood after addition of CaCl2 (100mM). Emicizumab plasma concentrations (EmiC) were measured by the modified calibrated one stage FVIII assay. We considered for TGA lag-time (LT) endogenous thrombin potential (ETP) and peak-thrombin (PH); for NATEM clotting-time (CT), clotting-firmness-time (CFT), time-to-maximum-clotting-firmness (MCF-t). Spearman’s Rho coefficient was used to assess the correlation between variables.

Results: Sixteen patients on emicizumab prophylaxis (aged 17-64 years) were included in the study. Three were positive for FVIII inhibitors. Results for NATEM and TGA are reported in Table 1.
When assessing the correlation with EmiC, NATEM-CT, NATEM-CT+CFT and NATEM-MCF-t were inversely correlated with EmiC (CT rho=-0.536, p< 0.05; CT+CFT rho=-0.515, p< 0.05; MCF-t rho=-0.561, p< 0.05). TGA-ETP and TGA-PH were positively correlated with EmiC (ETP rho= 0.507, p< 0.05; TGA-PH rho=0.643, p< 0.01). TGA and NATEM were inversely correlated (CT vs ETP, rho=-0.771, p< 0.001; CFT vs ETP, rho= -0.765, p< 0.001; CT+CFT vs ETP rho=-0.805, p< 0.001), Figure 1.

Conclusion(s): Our analysis of 16 patients on emicizumab prophylaxis shows that NATEM and TGA correlate with each other and with the concentration of emicizumab. Dose-adjustment of emicizumab based on laboratory testing is currently not required. However, our preliminary data suggest that NATEM and TGA might be useful to help managing special situations requiring monitoring with a global test, such as surgeries or concomitant treatment with bypassing agents.