PB0173 - Global coagulation assays in hemophilic patients on emicizumab prophylaxis, with and without partially neutralizing anti-drug antibodies

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, MA

Collaboratore Professionale di Ricerca
Fondazione IRCCS Cà Grand Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
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
GN

Gabriella Nicolò

Research Nurse
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Department of Healthcare Professions, Milan, Italy
Milano, Lombardia, Italy
GC

Gianluca Cafasso

MD
Division of Hematology, University of Milan, Milan, Italy.
Milan, Lombardia, Italy
Eugenia Biguzzi, MD

Hematologist
Hematology clinic, Oncology Institute of Southern Switzerland, EOC
Bellinzona, Ticino, Switzerland
Cristina Novembrino, PhD

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

Carla Valsecchi

Biologist
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milano, Lombardia, Italy
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 development of partially neutralizing anti-drug antibodies (ADA) might reduce emicizumab efficacy, but the effect on global coagulation assays is unknown.

Aims: To investigate the ability of non-activated thromboelastometry (NATEM) and thrombin generation assay (TGA), to reflect the biological effect of the presence of ADA.

Methods: We performed a cross-sectional study in patients with severe hemophilia A (HA) on emicizumab prophylaxis with and without partially neutralizing ADA. TGA was assessed with a homemade method upon addition of tissue-factor (1pM) and synthetic phospholipids (1µM) to plasma. Emicizumab plasma concentration (EmiC) was measured by a modified calibrated one stage FVIII assay, ADA were searched for with western blot method. NATEM was measured on citrated whole blood after addition of CaCl2 (100mM). Student’s T test for unpaired samples was used.

Results: Two patients aged 10 and 79, with persistent partially neutralizing ADA occurring after their 9th exposure, and 14 patients without ADA were enrolled. After 6 months of follow-up, the two patients with ADA and decreased EmiC reported no bleeding. Mean EmiC was 62.6 ug/ml in patients without ADA and 25.9 ug/ml in patients with ADA. When analyzing the coagulation with global assays in ADA patients, NATEM showed a delay in clot activation but the clotting formation was sustained and within the control range, as reported in Table 1 and Figure 1. When the TGA was carried out, the lagtime was not prolonged in comparison to controls, and again the endogenous thrombin potential and peak height were within control range, as shown in Table 1.

Conclusion(s): Our results show that despite decreased emicizumab level and prolonged aPTT, the coagulation of our patients was comparable to the controls when assessed with global coagulation tests, reflecting the absence of bleedings in vivo in two patients with ADA.