(MED-FR-10.3) Surgery with non-factor therapy

The approval of the factor VIII mimetic emicizumab and 2017/2018 and of the anti-TFPI inhibitors marstacimab and concizumab in 2024 has afforded subcutaneous prophylactic treatment options for people with hemophilia with and without inhibitors. None of these agents correct the coagulation defect fully and may need rescue hemostatic agents for better protection during hemostatic challenges such as surgeries. To date, we do not have clinical trials to provide data to guide the approach to the surgical patient for any of these agents.
For emicizumab, we have observational data from the label enabling trials, case reports and real-world case series that guide the approach to the surgical patient. These suggest that minor surgeries may be conducted without additional agents in some patients on emicizumab, but bleeding can occur. For major surgeries, additional hemostatic prophylaxis in the form of factor VIII concentrate for the non-inhibitor patients and recombinant factor VIIa or recombinant porcine factor VIII (rpFVIII) for inhibitor patients would be recommended. Concurrent treatment with rpFVIII in patients on emicizumab, however poses a challenge monitoring accurate factor VIII activity (cannot utilize one stage assay on emicizumab and chromogenic activity underestimates the activity of rpFVIII).
The management of surgical patients on marstacimab and concizumab is much less defined as there is next to no published data. Minor procedures could potentially be done on ongoing anti-TFPI prophylaxis. For major surgeries, a temporary discontinuation of anti-TFPI therapy and hemostatic prophylaxis with factor VIII or IX concentrate or bypassing agent should be considered. This is particularly important consideration in patients with higher tissue factor expression such as those with atherosclerosis, cancer or major trauma. If anti-TFPI therapy is continued, it would be important to check for potential drug clearing antibodies pre-operatively.