Coagulation Potential in Haemostatic Agents Concomitant With Low Concentration of Emicizumab Under Severe Haemophilia A State.

Background: Steady-state plasma concentrations of emicizumab in people with haemophilia A (PwHA) range from approximately 30 to 50 µg/mL, although some PwHA treated effectively with low doses of emicizumab have been reported. Little information is available, however, on the coagulation potential of bypassing agents (BPAs) under low concentration of emicizumab.

Aim: To assess the coagulation potential of BPAs in PwHA plasma at low concentration of emicizumab.

Methods: In FVIII-deficient plasmas spiked with emicizumab (2.5-10 µg/mL), concomitant effects of FVIII (1.0 IU/mL) or BPAs (recombinant (r)FVIIa; corresponding to 90 and 180 µg/kg, activated prothrombin complex concentrates (aPCC); 50 and 100 IU/kg, plasma-derived FVIIa/FX (pd-FVIIa/FX); 60 and 120 µg/kg) were assessed by tissue factor-triggered thrombin generation assay. In 10 emicizumab-treated PwHA plasmas on the loading and maintenance phases (mean plasma emicizumab concentration; 15 ± 2 and 50 ± 4 µg/mL, respectively), coagulation potential in them spiked with BPAs (rFVIIa 90, 270 µg/kg, aPCC 50 IU/kg and pd-FVIIa/FX 60 µg/kg) was monitored.

Results: The Peak thrombin (PeakTh) in FVIII-deficient plasma spiked with emicizumab (2.5-10 µg/mL) and FVIII was comparable to that spiked with FVIII alone, and that spiked with emicizumab and BPA were mildly to evidently greater than that spiked with BPA alone. In emicizumab-treated PwHA plasmas, the aPCC or pd-FVIIa/FX increased coagulation potentials. The rFVIIa (90 µg/kg) did not enhance coagulation potentials on the loading phase but improved them on the maintenance phase. The rFVIIa (270 µg/kg) enhanced coagulation potentials on the loading phase.

Conclusion: We should adjust BPA dosage in PwHA under low concentration of emicizumab.