Single Centre Experience of Surgery Management of Patients with Von Willebrand’s Disease Using High Purity Von Willebrand Factor Concentrate with Low Factor VIII Content
Authors: Wiles Natasha M , Rangarajan Savita 
Published: April 2020

Abstract
Good haemostatic control is paramount for surgery in patients with von Willebrand’s disease (VWD) and can be achieved with either desmopressin or plasma derived von Willebrand factor (VWF). Wilfactin is a plasma-derived von Willebrand factor concentrate with a low FVIII content. It was developed for the treatment of VWD and has been shown to produce safe and efficacious haemostasis, either alone or with supplementary FVIII. We report our experience in a retrospective study of all patients with VWD who underwent at least one invasive or surgical procedure during 1997 to 2001 and received Wilfactin. There were 30 evaluable patients (Table 1), all with either contraindications or unresponsive to desmopressin. The target VWF activity was 80–100 iu/dl and monitored in patients on continuous infusion and those with severe VWD or undergoing complicated procedures. Efficacy was primarily determined clinically. Thirty patients had a total of 75 surgical or invasive procedures. Of these, 64 were managed by bolus dosing and 11 by continuous infusion. Bolus dosing was given just prior to the procedure for 24 patients whose mean FVIII:C level was 47 iu/dl. Three patients had an additional priming bolus dose the day prior to the intervention and 2 patients received a bolus dose of FVIII in addition to the VWF just prior to the intervention. The mean FVIII:C of these patients was 32 iu/dl. The mean pre-operative dose per injection of VWF was 42 IU/kg. Continuous infusion was administered with an initial bolus dose of 40 iu/kg, followed by an infusion of 4 iu/kg until haemostasis or complete wound healing was achieved. The precise schedule and duration however, depended on the length and type of surgery, baseline VWF activity and post treatment values (Table 2). Of the 11 procedures managed with a continuous infusion; 5 were started the day before the procedure (D-1). Two received an extra bolus dose 12– 24 hours prior to the procedure. A FVIII bolus of 35 iu/kg with the VWF was given just prior to the intervention in 2 procedures on the same patient with severe VWD and FVIII levels of 2 iu/dl. Haemostatic efficacy for both bolus and continuous infusion was good with only one bleeding episode recorded, due to a surgical bleed requiring re-intervention. VWF activity and FVIII levels were within target range, and FVIII levels were maintained at between 90 and 175 iu/dl. No patients developed a thrombosis and there was no record of inhibitor formation to date. Our experience with Wilfactin in surgical management has been good. Bolus dosing was used primarily for minor procedures or patients with mild VWD. For more complicated procedures or severe VWD, continuous dosing was used. Only 2 patients received co-administration of FVIII. The low FVIII content in Wilfactin is reassuring in many cases, avoiding the post operative high Factor VIII levels and risk of thrombosis.
Table 1. Patient demographics
No. of patients (N) Male/Female (N) Mean age at surgery (n) Mean VWF activity (Ricof) iu/dl Mean FVIII level iu/dl * 14 procedures in paediatric patients VWD Type 1 21 6/15 37 (6–70) 29 (&lt;10–69) 54 (6–120) VWD Type 2 7 1/6 22 (7–37) 10 (5–13) 37 (23–48) VWD Type 3 2 1/1 49 (40–58) 7 (5–10) 5 (2–8) Total 30 8/22 34* (6–72) 15 overall mean 32 overall mean
Table 2. Continuous infusion: Schedule and Procedures
Patient Type VWF Activity iu/dl FVIII:C iu/dl Intervention Infusion initiation day 12–24hr Pre infusion Bolus VWF (iu) Factor VIII Bolus (iu) Treatment duration (days) 3 &lt;10 8 Orthopaedic surgery D 0 Yes 4000 No 5 Orthopaedic surgery D-1 No No 6 1A 7 31 ENT surgery D-1 No No 2 3 &lt;5 2 ENT surgery D-1 No No 2 ENT surgery D 0 No Yes D0 1 Orthopedic surgery D 0 No Yes D0 2 1b 69 81 Gynaecological surgery D 0 No No 5 1b 59 120 Gynaecological surgery D-1 No No 3 1 &lt;10 22 General surgery D 0 No No 4 1 &lt;10 18 Orthopedic surgery D-1 No No 3 Orthopedic surgery D 0 Yes 3000 No 3