During the last decade, the development of improved and novel approaches for the 
treatment of hemophilia A has expanded tremendously. These approaches include 
factor VIII (FVIII) with extended half-life (eg, FVIII-Fc and PEGylated FVIII), 
monoclonal antibodies targeting tissue factor pathway inhibitor, small 
interfering RNA to reduce antithrombin expression and the bispecific antibody 
ACE910/emicizumab. Emicizumab is a bispecific antibody recognizing both the 
enzyme factor IXa and the substrate factor X. By simultaneously binding enzyme 
and substrate, emicizumab mimics some part of the function exerted by the 
original cofactor, FVIII, in that it promotes colocalization of the 
enzyme-substrate complex. However, FVIII and the bispecific antibody are 
fundamentally different proteins and subject to different modes of regulation. 
Here, we will provide an overview of the similarities and dissimilarities 
between FVIII and emicizumab from a biochemical and mechanistical perspective. 
Such insight might be useful in the clinical decision making for those who apply 
emicizumab in their practice now or in the future, particularly in view of the 
thrombotic complications that have been reported when emicizumab is used in 
combination with FVIII-bypassing agents.