Emicizumab, the factor VIII mimetic bispecific monoclonal antibody: effects on thrombin generation and thromboelastometry

Background: Emicizumab is used for prophylaxis of patients with hemophilia A. Because it is used at a fixed dose that is not based on laboratory testing, evaluation of its activity is occasionally needed. Global coagulation procedures such as thrombin generation assays (TGAs) or thromboelastometry are obvious candidates for testing. Information on the significance of TGA or thromboelastometry parameters in patients treated with emicizumab is limited. Objectives: We performed a 2-step study to gain insight into the pattern of variation of TGA or thromboelastometry results in patients treated with emicizumab. Methods: The first experiment was an in vitro investigation of the best conditions in terms of TGA reagent composition needed to show the best dose-response of TGA parameters and emicizumab concentrations. In the second, we evaluated ex vivo the correlation of TGA or thromboelastometry parameters vs emicizumab concentrations achieved by patients receiving prophylaxis. Results: While TGA thrombin peak and endogenous thrombin potential (ETP) showed good dose-response with emicizumab concentrations, lag time and time-to-peak did not. The best TGA condition in terms of reagent composition was 1 pM tissue factor plus 1 μM phospholipids. There was a strong correlation between thrombin peak or ETP and emicizumab concentrations. The correlation was highly significant for thromboelastometry clotting time, but only when the procedure was performed without exogenous triggers. Based on the above correlations, we estimated the value of TGA or thromboelastometry parameters corresponding to the critical values of 40 or 80 μg/mL emicizumab. Conclusion: TGA thrombin peak or ETP performed at low tissue factor and phospholipid concentrations should be used to evaluate emicizumab activity. Thromboelastometry clotting time is valuable when performed without exogenous triggers.