Perioperative use of efanesoctocog alfa in Hemophilia A: A dual-center real-world study Free

Background:

Persons with Hemophilia A (PWH) are at high risk of bleeding during and after surgery. Standard perioperative management requires frequent factor VIII infusions to maintain hemostatic levels, which is burdensome. Efanesoctocog alfa (ALTUVIIIO®) is a first-in-class, ultra–extended half-life FVIII concentrate that received FDA approval in 2023 for routine prophylaxis and perioperative bleeding management. It is engineered as a B-domain–deleted recombinant FVIII protein fused to the Fc domain of human IgG1, the D′D3 domain of von Willebrand factor (VWF), and XTEN® polypeptides. This design enables independence from the VWF half-life ceiling, prolonging circulation time and affording higher sustained FVIII activity. Clinical trials demonstrated excellent surgical hemostasis with Efanesoctocog alfa, but real-world perioperative outcomes data with larger numbers of subjects remain limited. We therefore sought to explore perioperative hemostasis properties in the real-world setting to evaluate dosing, administration frequency, hemostatic effectiveness and safety of perioperative Eefanesoctocog alfa administration in adult PWH.

Methods:

We performed a retrospective review of all surgeries performed between March 1, 2023, and June 30, 2025 at two Hemophilia Treatment Centers in the United States (University of San Diego California and Orthopaedic Center Los Angeles). Surgical procedures were classified per ISTH criteria as major or minor. Inclusion criteria included PWH > age 18, who received at least one preoperative dose of Efanesoctocog alfa, plus/minus additional postoperative doses administered at the discretion of treating physicians. Patients with active factor VIII inhibitors were excluded. Data collected included demographics, hemophilia severity, prior prophylaxis, dosing and frequency of Efanesoctocog alfa, perioperative antifibrinolytic use, bleeding outcomes, rescue factor therapy, transfusion requirements, complications, and bleeding events within 30 days postoperatively.

Results:

Fifty-eight surgeries were performed in 48 patients. The median age was 43 years (IQR 38–60); 52 of 58 surgeries (90%) were in male patients. Severe, moderate and mild hemophilia A was present in 26 (48%), 3 (5%) and 26 cases (48%), respectively (data missing in 3 cases). Twenty-five (47%) procedures were classified as major and 28 (53%) as minor, respectively. Intraoperative hemostasis was achieved in all cases. Postoperative bleeding occurred in 6 surgeries (10%), but was all minor (wound oozing, hematuria, mucosal) and could be managed conservatively. Rescue factor therapy with standard half-life rFVIII was used in 4 cases (7%). One patient (1.7%) required red blood cell transfusion. Antifibrinolytic therapy was used in 37 of 58 surgeries (64%). Of those, 17 cases (46%) received intravenous antifibrinolytics as part of the standard surgical protocol, 12 cases (32%) received oral antifibrinolytics as adjuvant therapy, and 8 cases (22%) received both IV and oral routes. No thromboembolic events were observed. A second postoperative dose of Efanesoctocog alfa was administered in 20 surgeries (35%), most commonly on postoperative day 3 or 4. Median hospital length of stay was 2 days for major surgeries and 0 days for minor procedures. Four patients (7%) experienced minor bleeding within 30 days postoperatively, including 3 with nonsurgical-site bleeding (e.g., spontaneous mucosal or muscle bleeds) and 1 with expected residual bleeding following a prostate biopsy. No patient experienced unexpected bleeding from the surgical site, or developed venous thromboembolism

Conclusions:

Perioperative Efanesoctocog alfa administration provided effective surgical hemostasis, whereby a single preoperative outpatient dose was sufficient for most procedures. These observations are encouraging since Efanesoctocog alfa seems to not only facilitate but also alleviate outpatient management, advantageous to reduce management burden for patients and health care staff alike.