Mechanisms of action of novel nonfactor therapeutics for hemophilia. Hemostatic nonfactor agents in varying phases of development include substitution therapies (emicizumab, BS027125) for FVIII that can restore factor Xa generation and rebalancing therapies, which knock down or disrupt the natural anticoagulants (small interfering RNA to AT and PS, monoclonal antibodies to protein C and TFPI, and an APC-specific serpin), to augment hemostasis.