Successful surgical management in severe hemophilia A patients using efanesoctocog alfa: A two-case experience undergoing orthopedic surgery

Abstract Introduction: Efanesoctocog alfa (Altuviiio®/Altuvoct®) is a newly approved, high-sustained recombinant factor VIII (rFVIII) with ultra-long half-life and activity due to its fusion with XTEN® polypeptides and the D'D3 domain of von Willebrand factor. It enables once-weekly prophylaxis and may offer simplified perioperative management in patients with hemophilia A. However, real-world data on its use in the surgical setting remain limited. We present two cases of major orthopedic surgery in patients with severe hemophilia A managed with efanesoctocog alfa, highlighting its pharmacokinetic advantages and clinical efficacy. Objective: To evaluate the efficacy, safety, and pharmacokinetic profile of efanesoctocog alfa in perioperative management of orthopedic surgery in severe hemophilia A patients. Methods: Two male patients (ages 40 and 62 years) with severe hemophilia A (<1% FVIII activity) without inhibitor history, were on stable weekly prophylaxis with efanesoctocog alfa (50 IU/kg). Both underwent elective orthopedic procedures: right total hip arthroplasty (Patient 1) and radial head arthrolysis (Patient 2). Perioperative factor coverage was tailored according to FVIII activity levels -using one-stage clotting assay (FVIII:C)- and clinical response (bleeding or thrombotic complications). Results: Patient 1 (hip arthroplasty) received his routine prophylactic dose 48 hours prior to surgery. A FVIII:C level measured 24 hours post-dose showed 123%. On the day of surgery, a single preoperative dose of 25 IU/kg was administered. Postoperative FVIII:C levels were 74.7% at 24 hours and 51% at 48 hours, with 25 IU/kg given after each measurement. The patient was discharged at 48 hours and received one final dose of 25 IU/kg on day 3. Regular weekly prophylaxis was resumed on day 5. He also received thromboprophylaxis with low molecular weight heparin for 6 days. No bleeding episodes, thrombotic events, need for transfusion, or inhibitor development occurred. Hemostatic response was assessed as excellent. Patient 2 (radial head arthrolysis) received his last prophylactic dose 72 hours before surgery. A single preoperative dose of 22 IU/kg was administered immediately prior to the procedure. At 24 hours post-op, remarkably FVIII:C was 153%, and no further dose was given. The patient was discharged 48 hours after surgery and received a single additional dose of 22 IU/kg. Weekly prophylaxis was resumed on day 4. No hemorrhagic or thrombotic complications were observed, and no transfusions or inhibitor development occurred. The surgical course was uneventful with excellent hemostatic response. Safety Profile: Both patients demonstrated excellent tolerance. No thrombotic complications occurred despite adequate hemostatic levels. No hemorrhagic events were documented throughout perioperative period. Inhibitor screening remained negative at follow-up. Transfusion requirements were completely avoided. Patient 1 received standard thromboprophylaxis with heparin for 6 days without complications. Clinical Outcomes: Hemostatic response was classified as excellent in both cases. Surgical procedures were completed without bleeding complications. Wound healing progressed normally without delayed complications. Both patients achieved expected functional outcomes from their respective procedures. Conclusions: Both patients underwent successful orthopedic surgeries with minimal perioperative exposure to efanesoctocog alfa. Each case required only one preoperative dose plus a limited number of postoperative infusions. The high and sustained FVIII levels achieved with relatively low factor consumption supported effective hemostasis throughout the perioperative period, allowing early discharge and rapid return to baseline prophylaxis. These cases illustrate the potential advantages of efanesoctocog alfa in surgical settings, including simplified dosing schedules, reduced factor consumption, and a favorable safety profile. Importantly, no thrombotic or hemorrhagic complications occurred, and no patients required transfusions or developed inhibitors. These findings support the use of efanesoctocog alfa as a safe and efficient option for perioperative management in hemophilia A, especially in high-risk procedures such as orthopedic surgery. Further studies in larger cohorts are warranted to confirm these observations.