VPB0171 - The effect of anti-coagulant agents against in vitro hemophilia A plasma coagulation and fibrinolysis potential in the presence of emicizumab

Background: Emicizumab is a factor (F) VIII-function mimetic antibody for the treatment of people with hemophilia A (PwHA) with or without inhibitors. Infection can cause varying degrees of hemostatic dysfunction, especially bacterial infection, which can lead to a pro-coagulant state.
There is limited information about coagulation and fibrinolysis status in infected PwHA treated with emicizumab and the use of anti-coagulant agents in such cases.

Aims: In this study, we investigated how anti-coagulant agents affect the balance of coagulation and fibrinolysis in PwHA plasma spiked with emicizumab.

Methods: PwHA plasma was supplemented with 50 μg/mL of emicizumab and anti-coagulant agents (heparin, nafamostat mesylate (NM), recombinant thrombomodulin(rTM)). PwHA plasma spiked with 100 IU/dL of FVIII was used as a normal reference. The coagulable and fibrinolytic status of plasma was measured by Thrombin/Plasmin-Generation Assay (T/P-GA) and Clot-Fibrinolysis Waveform Analysis (CFWA).

Results: In T/P-GA and CFWA, spiking PwHA plasma with emicizumab improved coagulation function but had no effect on fibrinolytic function. Adding heparin, NM, and rTM to normal reference plasma inhibited both the peak thrombin (Th-Peak) and the peak plasmin (Plm-Peak) in T/P-GA. In CFWA, heparin, NM, and rTM also reduced the maximum coagulation velocity (|min1|) and the maximum fibrinolytic velocity (|FL-min1|). The addition of heparin, NM, and rTM to PwHA plasma spiked with emicizumab suppressed the Th-Peak and the Plm-Peak of T/P-GA. In CFWA, heparin, NM, and rTM also reduced the |min1|and the |FL-min1|. These results showed a tendency similar to the inhibitory effect of anti-coagulant agents on coagulation and fibrinolysis function in normal reference plasma.

Conclusion(s): Anti-coagulant agents exhibit inhibitory effects on the coagulation and fibrinolytic function in PwHA plasma spiked with emicizumab similar to those in normal reference plasma.