Experience With Minor Surgeries in People With Hemophilia a or B With or Without Inhibitors Receiving Fitusiran
Year: 2026
Type: article
Abstract: Introduction While non-factor hemophilia therapies are increasingly available, perioperative management data are limited. Fitusiran is an antithrombin (AT) to increase thrombin generation and restore hemostasis in people with hemophilia (PwH) A/B, with or without inhibitors. Perioperative hemostasis in this setting is typically managed according to bleed management guidelines (BMG), which call for reduced-dose and/or reduced-frequency coverage with clotting factor concentrates (CFC) or bypassing agents (BPA). Fitusiran prophylaxis has previously been evaluated in 60 major surgeries in PwH A/B, with same-day hemostatic control rated excellent/good in 39/41 (95%) cases. Objectives To describe the hemostatic outcomes of minor surgeries conducted while on fitusiran prophylaxis in PwHA/B aged ≥12 years, with or without inhibitors. Methods All minor surgeries in the fitusiran clinical development program until June 2023 (Phase 2 OLE, Phase 3 ATLAS-INH, ATLAS-A/B, ATLAS-PPX and ATLAS-OLE) were evaluated, including AT-based dose regimen (AT-DR; starting dose of 50 mg once every two months, targeting AT activity of 15–35%) and original dose regimen (ODR; 80 mg fixed once monthly). Informed consent and ethics committee approval were obtained for all studies. Procedures performed while on fitusiran with AT activity <60% were included. Minor surgeries were defined as any invasive operative procedure in which only skin, mucous membranes, or superficial connective tissue were manipulated and did not meet the criteria for major surgery. Perioperative hemostatic control was assessed by the investigators/surgeon using the ISTH 4-point response scale (excellent/good/moderate/poor) on day of surgery. Perioperative antifibrinolytics use was reported from day of surgery until Day 7 post surgery. Results Seventy-one minor surgeries were performed in 44 participants (AT-DR, n = 45; ODR, n = 26). Most frequent minor surgeries included dental (n = 21), soft tissue (n = 12), abdominal (n = 12), central or peripheral access-related (n = 10), orthopedic (n = 7), plastic/reconstructive (n = 4), airway management and emergency (n = 3), and ophthalmic (n = 2) procedures. Of the 22 surgeries with a hemostatic control assessment on the day of surgery, 21 (95%) were rated excellent/good and 1 (5%) moderate. ATIII concentrate was not used to reverse the pharmacodynamic effect of fitusiran in 99% (n = 70/71) of minor surgeries. Antifibrinolytics were not utilized in 67% (n = 14/21) of dental and 87% (n = 62/71) of all minor surgeries. In 18% (n = 13/71) of minor surgeries, neither antifibrinolytics nor CFC/BPA were required. Median (range) duration of antifibrinolytic use was 4 (1–8) days. No major treatment-related safety concerns were identified perioperatively. Conclusions Minor surgeries can be safely and effectively conducted in patients receiving fitusiran prophylaxis, irrespective of inhibitor status. On the day of the surgery, 95% of minor procedures in PwH, with or without inhibitors, achieved excellent/good hemostatic control under fitusiran prophylaxis. ATIII concentrate was used to reverse fitusiran's AT-lowering effect in only a single case, indicating that routine reversal is not required. Most procedures were managed without antifibrinolytics. Overall, these data support the perioperative management of PwH receiving fitusiran. Funding Sanofi. Disclosures ©American Society of Hematology (2025). Reused with permission.
Institutions: University of Michigan, Michigan Medicine, Peking Union Medical College Hospital, Ege University, Fiona Stanley Hospital, Daejeon Eulji Medical Center, Eulji University, University Hospital Zurich, Tel Aviv University, Sheba Medical Center, Royal Prince Alfred Hospital, Kirov Research Institute of Hematology and Blood Transfusion FMBA, University of Southern California, Children's Hospital Los Angeles, Nemours Children's Health System, St.John's Medical College Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223156863