Major Orthopedic Surgeries Conducted Under Fitusiran Prophylaxis in People With Hemophilia a and B, With and Without Inhibitors
Year: 2026
Type: article
Abstract: Introduction Fitusiran is an antithrombin (AT)-lowering therapeutic that increases thrombin generation to restore hemostasis in people with hemophilia (PwH) A/B, with and without inhibitors. Breakthrough bleed management guidelines (BMG) with reduced dose and frequency of clotting factor concentrates (CFC)/bypassing agents (BPA) were recommended for perioperative management. Objectives To present hemostatic outcomes and provide case reviews of orthopedic surgeries performed in PwHA/B aged ≥12 years receiving fitusiran prophylaxis, regardless of inhibitor status. Methods All major orthopedic surgeries in the fitusiran clinical program until 14 June 2023 were evaluated, including participants on AT-based dose regimen (AT-DR) and fixed 80 mg once-monthly dose (ODR). Procedures conducted during fitusiran prophylaxis with AT levels <60% were included. Major orthopedic surgeries were defined as operations on a joint or bone and associated soft tissue. Procedure management was at investigator/surgeon’s discretion. Perioperative hemostatic control was assessed using the ISTH 4-point response scale (excellent/good/moderate/poor) on the day of surgery. Results Nineteen major orthopedic surgeries (AT-DR, n = 7; ODR, n = 12) were performed in 16 participants. Hemostatic control was excellent/good in 13/15 (87%) and moderate in 2/15 (13%; knee arthroplasty and total knee replacement, both treated with BPAs) surgeries with an assessment on the surgery day. Reduced doses of CFC/BPAs were used in 15/19 (79%) surgeries, per BMG. A tibial metal plate/screw fixation was managed successfully with fitusiran prophylaxis without any CFC/BPA. On the surgery day, AT level was 9.1% and hemostatic control was good; no complications were reported in the perioperative period. AT concentrate (ATIII) was used per investigator discretion in two participants, with excellent hemostatic control on the day of the surgery in one (internal fixation for femoral/patella fractures) and moderate in the other (right knee arthroplasty). Antifibrinolytics were not used during major orthopedic surgeries. One postoperative lower limb deep vein thrombosis occurred during a knee arthroplasty in the setting of pre-existing thrombotic risk factors, including morbid obesity restricting mobility and excessive FVIII dosing exceeding BMG and ISTH recommendations; fitusiran was permanently discontinued 14 days after surgery due to this event. No postoperative safety findings or complications were reported when BMG were followed. Conclusion Major orthopedic surgeries can be safely and effectively performed in PwHA/B, with and without inhibitors, receiving fitusiran prophylaxis using reduced CFC/BPA doses as per BMG, highlighting the benefit and efficacy of reduced CFC/BPA consumption with fitusiran prophylaxis. Perioperative ATIII administration is not necessary. Postoperative thrombosis in a participant with pre-exisitng increased thrombotic risk after dosing above the BMG highlighted the importance of BMG adherence. Funding Sanofi.
Institutions: Massachusetts General Hospital, Hôpital Necker-Enfants Malades, Ege University, Fiona Stanley Hospital, Nanfang Hospital, Daejeon Eulji Medical Center, Eulji University, University of Padua, Center for Inherited Blood Disorders, Sanofi (United States), Sanofi (France), St.John's Medical College Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223141934