Usefulness of global assays to monitor treatment of a patient with Hemophilia A switching from factor to non-factor replacement therapy

Objective Hemophilia A is a rare bleeding disorder characterized by the deficiency of coagulation factor VIII (FVIII). Emicizumab is a humanized bispecific antibody which acts as a bridge between activated factor IX (FIXa) and factor X (FX), thus replacing the hemostatic function of the missing FVIII. However, emicizumab interferes with conventional coagulation assays, precluding the possibility to evaluate the degree of correction of the hemostatic competence of the patient in response to treatment. Global coagulation assays (GCA) could be an interesting alternative. Here we studied thrombin generation (TG) and fibrin clot formation (FCF) profiles in a 18 years old patient switching from factor replacement to emicizumab treatment. Our aim was to investigate whether GCA could be used to successfully monitor non-factor replacement therapy with emicizumab.

Material and Methods TG was measured with the reference method Calibrated Automated Thrombogram (CAT) and with the new fully automated ST Genesia system (Stago, Asnières-sur-Seine, France). FCF was measured with the innovative Thrombodynamics Analyzer (Hemacore, Russia) which monitors the spatio-temporal (tissue factor [TF]-dependent and -independent) dynamics of coagulation. The patient received subcutaneously a weekly dose of Hemlibra® (3 mg/kg per body weight W1-4; 1.5 mg/kg from W5 onwards). Response to treatment was monitored weekly during a two months period. Emicizumab was measured with a modified aPTT-based assay. Analyses of TG and FCF were performed in platelet poor plasma in presence of TF (1 pM or 100 pmoles/m2 respectively) and phospholipids (4uM).

Results Treatment with emicizumab improved TG and FCF compared to baseline. FCF normalized already after one week of treatment, reaching a plateau that lasted until the end of the monitoring two months later. TG, which normalized after two weeks of treatment, and FCF in presence of emicizumab were in the lower normal range and much lower that the values observed after replacement with rFVIII. Of note, increasing emicizumab concentrations observed after W1 did not further improve TG or FCF parameters.

Conclusion According to this limited experience, emicizumab seems to improve the hemostatic potential in an “all-or-nothing” manner. TG assays are a promising tool to evaluate the hemostatic status of patients receiving non-factor therapy. Further investigations are needed to confirm this observation.

Publication History

Article published online:
18 June 2021