Perioperative Management in Persons With Haemophilia on Rebalancing Therapies: A Narrative Review.

Abstract

Introduction: Perioperative management in haemophilia often requires on-demand use of clotting factor concentrates (CFC) and/or bypassing agents. Rebalancing agents (fitusiran, concizumab, marstacimab) offer a novel approach to prophylaxis by modulating endogenous anticoagulant pathways to restore haemostatic balance. While these therapies offer advantages, such as subcutaneous delivery and factor-independent mechanisms, thromboembolic risk and optimal concurrent on-demand CFC/bypassing agent dosing perioperatively are not understood.

Aim: To evaluate available evidence on the efficacy and safety of rebalancing therapies in haemophilia A or B in the perioperative setting.

Methods: A narrative review of perioperative use of rebalancing therapies was conducted using targeted searches of PubMed, Scopus, and major international haematology conference abstracts through to December 2025.

Results: Evidence suggests rebalancing therapies may contribute to effective perioperative haemostasis, often with reduced dosing or frequency of CFC or bypassing agents, though data is overall limited. Early studies of fitusiran and concizumab report generally favourable haemostatic outcomes in minor and selected major procedures. Perioperative bleeding events with fitusiran use are reported most often as mild to moderate and haemostasis was rated excellent/good in 90%-95% of cases. Similarly, concizumab data show bleeding events in 39/94 surgeries, the majority of which were mild to moderate. Data for marstacimab is limited but suggest feasibility with temporary interruption and CFC support.

Conclusion: Limited perioperative evidence suggests that rebalancing therapies may contribute to acceptable haemostatic outcomes with reduced use of conventional haemostatic agents in selected settings. However, important clinical uncertainties remain, highlighting the need for further prospective studies.