PB0175 - Monitoring emicizumab with global coagulation assays

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Debora Bertaggia Calderara, PhD

Research Associate
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland

Co-Author(s)

AB

Ana Patricia P. Batista Mesquita Sauvage

Specialized clinical nurse
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
FG

Francisco Javier J. Gomez

Head technician
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
MZ

Maxime Grégoire G. Zermatten

Physician assistant
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
AA

Alessandro Aliotta, PhD

Research Associate
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
LV

Lucas Veuthey

PhD student
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
CP

Cindy Pereira Portela

MD student
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
LA

Lorenzo Alberio

Chief Physician, Associated Professor
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland

Background: Patients with Hemophilia A (PwHA) might benefit from treatment with emicizumab, a bispecific antibody mimicking the activity of the missing coagulation factor VIII (FVIII). Unlike FVIII, emicizumab does not require activation by thrombin and is immediately effective. Conventional aPTT-based FVIII assays are inadequate to monitor emicizumab efficacy, since even small concentrations shorten the aPTT, which does not reflect the real degree of coagulation correction achieved by emicizumab in vivo. The development of new tools able to predict the biological phenotype in patients under emicizumab treatment would have a high clinical impact.

Aims: To investigate the utility of global coagulation assays (GCA) in monitoring emicizumab.

Methods: Six PwHA received a weekly dose of Hemlibra® (Roche Pharma, Switzerland) (3 mg/kg per body weight W1-4, 1.5 mg/kg from W5 onwards). Thrombin generation (TG) was measured with Calibrated-Automated-Thrombogram (Stago, Asnières-sur-Seine, France). Fibrin clot formation (FCF) was measured with Thrombodynamics-Analyzer (Hemacore, Russia). Response to treatment was monitored weekly for two months. TG and FCF were compared to patient baseline values and to healthy controls (C).

Results: -Mean concentration of emicizumab showed a large variation among six PwHA;
-Compared to baseline values, TG and FCF significantly increased in PwHA after completion of the loading period (W5), reaching a plateau that lasted until the end of the monitoring;
-TG and FCF during the plateau phase remained at the lower limits of reference values measured in C;
-Patients having similar plasmatic plateau concentrations of emicizumab, showed different degree of TG and FCF improvement, which correlated with their clinical response.

Conclusion(s): In these six PwHA, emicizumab improved and maintained the hemostatic potential during monitoring. However, despite a similar dosage, patients showed individually variable responses to emicizumab. GCA appear to be a promising tool for evaluating the degree of coagulation correction exerted by emicizumab and to personalize patient therapy. Further clinical investigation is needed.