Essentials The activated partial prothrombin time (aPTT) cannot predict the 
activity of emicizumab (Emi). Adjusted clot waveform analyses using a 
prothrombin time (PT)/aPTT initiator were developed. Activity of Emi in the 
co-presence of factor VIII or bypassing agents was quantified. This assay is 
useful for assessing coagulation potential in Emi-treated hemophilia A.
SUMMARY: Background Emicizumab is an anti-activated factor IX/FX bispecific 
antibody that mimics activated FVIII cofactor function. Emicizumab does not 
require activation by thrombin, and its effect on shortening the activated 
partial thromboplastin time (APTT) is much greater than that of FVIII. 
Therefore, the APTT has limited utility in hemophilia A (HA) patients treated 
with emicizumab. Aim To evaluate the global coagulation potential of emicizumab. 
Methods Clot waveform analysis (CWA) with prothrombin time (PT)/APTT mixed 
reagents was used to define hemostatic monitoring protocols in HA patients. A 
modified parameter, adjusted-|min1| (Ad|min1|), was developed. Maximum and 
minimum percentage transmittance were defined as 100% and 0% in the 
precoagulation and postcoagulation phases, respectively. Ad|min1| was calculated 
as an index of the maximum velocity of the coagulation process. Results Ad|min1| 
obtained with mixed-trigger reagent (PT/APTT/buffer, 1 : 15 : 135) in the 
presence of emicizumab optimally corresponded to the conversion rate estimated 
in animals; 0.2-0.4 IU dL-1 equivalent FVIII per 1 μg mL-1 emicizumab). Ex vivo 
addition of emicizumab to HA plasma with or without inhibitors resulted in 
concentration-dependent increases in Ad|min1|, with some individual variations. 
The addition of various concentrations of FVIII to HA plasma mixed with 
emicizumab resulted in dose-dependent increases in Ad|min1|. Similarly, mixtures 
of activated prothrombin complex concentrate and emicizumab added to HA plasma 
resulted in dose-dependent increases in Ad|min1|. In contrast, enhanced 
coagulation potential appeared to be better defined by the clot time than by 
Ad|min1| in experiments using recombinant activated FVII. Conclusion The PT/APTT 
reagent-triggered adjusted CWA could provide a useful means of assessing global 
coagulation potential in emicizumab-treated HA patients, with enhanced activity 
neither masking nor being masked by FVIII or bypassing agents.