Nonfactor Replacement Treatment and Surgery in Haemophilia: Evidence From the Literature and Selected Clinical Cases

Introduction: Over the recent years, the introduction of nonfactor replacement (NFR) prophylaxis for haemophilia has allowed to reduce the burden of treatment and to offer effective prophylaxis also for patients with inhibitors, with an excellent successful prevention of spontaneous bleeding, often approaching a median annual bleeding rates close to 0. However, patients on NRF prophylaxis require traditional replacement treatment for breakthrough bleeds and to manage especially major surgery. Real-world experiences with the use of emicizumab are accumulating, showing excellent outcomes, while these are still significantly limited data available with rebalancing agents (concizumab, marstacimab and fitusiran). Aim: The present overview is focused on surgical procedures with nonfactor replacement prophylaxis. Methods: Review of the literature and report of personal experiences with the use of emicizumab and replacement treatment during surgery. Results: Combined used of emicizumab prophylaxis together with factor replacement in patients with Haemophilia A with and without inhibitors provided excellent results. Multiple elective orthopaedic procedures, oral and abdominal surgical interventions, and trauma surgery confirmed the feasibility of this combined approach, without significant side effects. Conclusions: The association of nonfactor prophylaxis with recombinant factors has provided safe, reproducible and effective results, with low rates of complications. However, the experience with rebalancing agents is still limited, and more real-world studies are needed to confirm the most appropriate approach.