Essentials Emicizumab mimics factor (F)VIIIa cofactor function, augments the 
intrinsic tenase activity. We assessed the emicizumab-driven hemostatic function 
in FXI-deficient plasmas. Emicizumab improved the coagulation potentials in 
severe FXI-deficient plasma. Emicizumab may provide a possibility for clinical 
application in patients with FXI deficiency. SUMMARY: Background Patients with 
factor (F)XI deficiency commonly present with markedly prolonged activated 
partial thromboplastin times (APTT), although bleeding phenotypes are 
heterogeneous. Emicizumab, a bispecific monoclonal antibody to FIX/FIXa and 
FX/FXa, mimics FVIIIa cofactor function on phospholipid (PL) surfaces. Antibody 
reactions were designed, therefore, to augment mechanisms during the propagation 
phase of blood coagulation. Aim To assess emicizumab-driven hemostatic function 
in FXI-deficient plasmas. Methods and Results Standard ellagic acid 
(Elg)/PL-based APTTs of different FXI-deficient plasmas (n = 13; FXI activity, 
< 1 IU dl-1 ) were markedly shortened dose dependently by the presence of 
emicizumab. To further analyze the effects of emicizumab, clot waveform analysis 
(CWA) in FXI-deficient plasmas with emicizumab, triggered by tissue factor 
(TF)/Elg demonstrated improvements in both clot times, reflecting the initiation 
phase, and coagulation velocity, which represents the propagation phase. 
Emicizumab also enhanced the TF/Elg-triggered thrombin generation in 
FXI-deficient plasmas dose-dependently although the degree of enhancement varied 
in individual cases. Thrombin generation with either FVII-deficient plasma or 
FIX-deficient plasma treated with anti-FXI antibody showed little or no increase 
by the co-presence of emicizumab, suggesting that the accelerated thrombin 
generation in FXI-deficient plasmas by emicizumab should depend on the 
FIXa-involved coagulation propagation initially triggered by FVIIa/TF. The 
ex vivo addition of emicizumab to whole blood from three patients with severe 
FXI deficiency demonstrated modest, dose-dependent improvements in Ca2+ 
-triggered thromboelastograms (NATEM mode). Conclusion Emicizumab appeared to 
improve coagulation function in severe FXI-deficient plasma, and might provide 
possibilities for clinical application in patients with FXI deficiency.