Minor Surgeries Safe to Perform in Patients Receiving Fitusiran Prophylaxis, With Julian Zorrilla, DO

Minor surgeries can be safely conducted for patients receiving fitusiran prophylaxis for hemophilia A/B, regardless of inhibitor status, according to a recent study.1

Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition by Julian Zorrilla, DO, a pediatric hematologist and oncologist at Nemours Children’s Health, these data emphasize the overall efficacy of fitusiran in hematology at large.1

Hemophilia A/B bleeding is caused by deficiencies in factor VIII and factor IX, respectively, which result in insufficient thrombin generation and disrupted hemostasis. Treatment strategies for restoring thrombin generation to achieve hemostasis relied for years on replacing or mimicking the missing factor. However, fitusiran, a subcutaneous prophylactic small-interfering RNA therapeutic, lowers antithrombin levels and increases thrombin generation irrespective of inhibitors.2

“One of the things we performed in analysis was to look specifically at what other hemostatic control options investigators had at their disposal, whether that would be regular factor products or products with bypassing agents traditionally used for those with inhibitors,” Zorrilla told HCPLive in an exclusive interview. “And so, we would take that into account depending on what minor procedures were performed.”

Zorrilla and colleagues examined all minor surgeries in the fitusiran clinical development program prior to June 2023, including patients on the original dose regimen of 80 mg fixed once monthly and the antithrombin-based dose regimen with a starting dose of 50 mg once every 2 months. For inclusion in the study, procedures had to have been conducted during fitusiran prophylaxis and when antithrombin activity was <60%.1

Investigators defined minor surgeries as any invasive operative procedure in which only skin, mucous membranes, and/or superficial connective tissue were manipulated. Additionally, perioperative hemostatic control was assessed by the investigators or surgeon based on the ISTH 4-point response scale on the day of the surgery. Perioperative use of antifibrinolytics was reported from the day of the surgery until day 7 post-surgery.1

A total of 71 minor surgeries were performed during fitusiran’s clinical development program, encompassing 44 patients. These 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). Overall, 26 surgeries were performed in patients with hemophilia on the original dose regimen and 45 in patients with hemophilia with the antithrombin-based dose regimen.1

Of 22 surgeries with a hemostatic control assessment on the day of the surgery, 21 cases were rated as excellent/goo,d and 1 case was rated as moderate. ATIII concentrate was not used to reverse the pharmacodynamic effect of fitusiran in 99% (n = 70/71) of minor surgeries. Additionally, a total of 67% (n = 14/21) of dental surgeries and 87% (n = 62/71) of all minor surgeries did not require the use of antifibrinolytics.1

Ultimately, Zorrilla and colleagues determined that minor surgeries can safely be conducted in patients experiencing fitusiran prophylaxis, regardless of inhibitor status. Most surgeries achieved excellent/good perioperative hemostatic control, based on the ISTH 4-point response scale, and reversal of antithrombin-lowering effects was rarely performed.1

“With fitusiran’s thrombogenic profile in ammonium clotting in those with hemophilia, one of the safety measures that we always look at has to relate to the instances of venous thromboembolism in patients while they’re on fitusiran,” Zorrilla said. “This is especially true when they’re going to surgery, whether it be major or minor.”

Editor's Note: Zorrilla reports no relevant disclosures.

References

1. Pipe S, Zhu T, Kavakli K, et al. Experience with minor surgeries in people with hemophilia A or B with and without inhibitors receiving fitusiran. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Pipe SW, Lissitchkov T, Georgiev P, et al. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025;9(5):1147-1158. doi:10.1182/bloodadvances.2024013900