Introduction: Emicizumab is used as hemostatic prophylaxis for patients with hemophilia A (PwHA), irrespective of the presence of inhibitors. Although bacterial infection can lead to a procoagulant state, there is limited information on coagulation and fibrinolysis potentials in emicizumab-treated PwHA and on the use of anticoagulants in such cases.
Aim: We examined whether anticoagulants affect the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab.
Methods: Plasma from PwHA was in vitro supplemented with emicizumab (50 μg/mL; emi-plasma) and anticoagulants (recombinant thrombomodulin (rTM), nafamostat mesylate (NM), unfractionated heparin (UFH), or low-molecular-weight heparin (LMH)). PwHA plasma spiked with rFVIII (1 IU/mL) was used as a reference (ref-plasma). The coagulation and fibrinolysis potentials in plasma was measured by thrombin and plasmin generation assay (T/P-GA) and clot-fibrinolysis waveform analysis (CFWA).
Results: In T/P-GA and CFWA, coagulation potentials (maximum coagulation velocity; |min1|, and peak thrombin; Th-Peak) in plasma rose with increasing concentrations of emicizumab and rFVIII, but fibrinolytic potentials (peak plasmin; Plm-Peak, and maximum fibrinolytic velocity; |FL-min1|) remained unchanged. Adding rTM, NM, and UFH to emi-plasma suppressed coagulation and fibrinolysis potentials, similar to ref-plasma. Regarding the heparin, UFH and LMH inhibited the improved coagulation in emi-plasma. UFH inhibited fibrinolysis as well, but LMH did not.
Conclusions: Anticoagulants could exhibit the inhibitory effects on the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab, similar to those in normal plasma.
Keywords: anticoagulants; bispecific antibody; coagulation; fibrinolysis; hemophilia A; infection.
© 2023 John Wiley & Sons Ltd.