Objective:
BAY 94-9027 is an extended–half-life recombinant factor VIII (FVIII) product. Efficacy in maintaining hemostasis during major surgery was evaluated in a subset of patients with severe hemophilia A in the phase 2/3 PROTECT VIII study.
Methods:
Patients aged 12–65 years requiring major surgery during PROTECT VIII or its ongoing extension were included in the analysis. Patients with severe hemophilia A undergoing major surgery who were not enrolled in PROTECT VIII but met all study inclusion and exclusion criteria also were eligible to participate. BAY 94-9027 dosing during the perioperative period was based on preoperative pharmacokinetic measurements and adjusted at the physician’s discretion. Types of procedures and duration of surgeries, BAY 94-9027 consumption on the day of surgery, intraoperative blood loss, surgeon assessment of hemostasis during surgery, and need for blood transfusion were evaluated.
Summary:
17 patients (median [range] age, 37 [13–61] years) underwent 20 major surgeries, including 15 orthopedic surgeries (9 joint replacements [hip, n=1; knee, n=6; ankle, n=2], 2 open synovectomies, 3 arthroscopies, and 1 thigh hematoma evacuation), 3 complex dental extractions, 1 penile prosthesis, and 1 inguinal hernia repair at data cutoff (January 2015). Median (range) surgical duration was 102 (17‒217) minutes, and median (range) total dose used on day of surgery, including preoperative, intraoperative, and postoperative infusions on that day, was 72.4 (43‒136) IU/kg. Median (range) number of FVIII infusions on the day of surgery was 2 (1–3), with 40% of procedures requiring only 1 infusion (preoperative) on that day. Following a median (range) presurgical dose of 52.1 (41–64) IU/kg, the median (range) FVIII level (chromogenic assay; measured in a central laboratory) immediately before the second infusion was 71.6 (44–140) IU/dL; median (range) time between the presurgical and second infusions was 12.3 (3.6–50.0) hours. Hemostasis during surgery was good (13/20; 65%) or excellent (7/20; 35%) for all procedures. Intraoperative blood loss was within expected ranges for all surgeries (median [range], 50 [0–1000] mL), and blood transfusions were required in 4 patients undergoing knee surgeries.
Conclusions:
BAY 94-9027 is efficacious in maintaining hemostasis during major surgeries in adolescents and adults with severe hemophilia A. Excellent or good hemostasis with blood loss as expected was achieved in all surgical procedures, which included major orthopedic surgeries (75% of all procedures), with 40% of patients requiring only a single infusion of BAY 94-9027 on the day of surgery.