Perioperative von Willebrand Factor and Factor VIII Kinetics in von Willebrand Disease Patients Treated With Different Clotting Factor Concentrates.

INTRODUCTION: Patients with von Willebrand disease (VWD) undergoing surgery require von Willebrand factor (VWF) and factor VIII (FVIII) supplementation for adequate haemostasis. Plasma-derived clotting factor concentrates differ in their VWF:FVIII activity ratios: high-ratio product (HRP, 10:1), intermediate-ratio product (IRP, 2.4:1), and low-ratio product (LRP, 1:1). These differences may affect FVIII kinetics. METHODS: This single-centre observational study included VWD patients undergoing surgery, treated with an HRP, IRP, or LRP, and with ≥2 perioperative VWF or FVIII measurements between 2009 and 2024. VWF and FVIII trajectories were assessed using linear mixed-effects models. Secondary endpoints were bleeding and venous thromboembolic events (VTE). RESULTS: In total, 123 patients were included; 63% underwent major surgery. Twenty-four patients received HRP, 61 received IRP and 38 received LRP. The median number of infusions was three across groups. Incremental VWF recoveries were 1.7 IU/dL per IU/kg for HRP, 1.3 for IRP, and 2.4 for LRP. FVIII recoveries were 2.5 for IRP and 2.7 for LRP. Over time, HRP showed higher mean VWF levels than IRP (Δ26 IU/dL; p = 0.010). HRP was associated with higher FVIII levels compared with IRP (Δ48 IU/dL; p < 0.001) and LRP (Δ35 IU/dL; p = 0.021). No difference was found between IRP and LRP. In patients receiving three consecutive infusions in 24 h, FVIII levels remained higher with HRP than IRP (Δ38 IU/dL; p = 0.019). No VTEs occurred. CONCLUSION: IRP and LRP led to greater initial VWF and FVIII peaks, whilst HRP produced more sustained FVIII elevation. Recognising these kinetic differences may guide tailored perioperative management of patients with VWD.