Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures

Abstract

Introduction: Von Willebrand Disease is a common inherited haemorrhagic disorder due to a deficiency of Von Willebrand Factor (VWF). In case of surgical procedures in patients who are not responsive or have contraindications to desmopressin, replacement therapy with VWF concentrates is indicated. Until recently, only plasma-derived VWF concentrates were available. A new recombinant VWF (rVWF) concentrate that contains no Factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France since 2018. Aim: Describe real-world experience of using rVWF in surgical procedures. Methods: Sixty-three surgeries for 55 patients were retrospectively analysed in 7 French haemostasis centres. Results: During minor surgeries, the median (range) number of infusions was 1 (1-8) with a preoperative loading dose of 35 (19-56) rVWF IU/kg and a total median dose of 37.5 IU (12-288). During major surgeries, the median (range) number of infusions was only 3 (1-14) with a median preoperative loading dose of 36 IU (12-51) rVWF IU/kg, and a total median dose of 108 IU (22-340) rVWF IU/kg. The overall clinical efficacy was qualified as excellent/good in 61 of the procedures (97%), moderate in 1 (1.5%) and poor in 1 (1.5%). There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events, anti-VWF antibodies or adverse events were reported. Conclusion: This French 'real-world' experience shows that a few infusions and low doses of rVWF provided effective prevention of bleeding in major and minor surgeries in inherited VWD, with no clinically significant safety concerns. K E Y W O R D S inherited von Willebrand disease, recombinant VWF, surgical procedure | 271 DESPREZ Et al. How to cite this article: Desprez D, Drillaud N, Flaujac C, et al. Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures. Haemophilia.

Outcomes in Patients With von Willebrand Disease Receiving Recombinant von Willebrand Factor on Demand and in Surgical Settings: Chart Review

“…15 Overall clinical efficacy for rVWF was also rated as excellent or good in 97% of surgeries (n = 63) in patients with VWD included in a retrospective analysis. 16 Importantly, rVWF did not result in any treatment-emergent adverse events (including hypersensitivity, thrombotic events, VWF inhibitor development, and transfusion-related infections) in a real-world population, consistent with the safety profile of rVWF demonstrated in clinical trials and a retrospective analysis of rVWF use in surgical procedures. [14][15][16] In this chart review, among patients receiving initial rVWF therapy at index, 10/11, 31/34, and 49/54 patients received rVWF therapy without FVIII for the treatment of spontaneous/traumatic bleeds, prophylaxis in preparation for surgery, or perioperative management (on or after the day of surgery), respectively.…”

“…The efficacy of rVWF in this chart review is consistent with clinical trial data derived from patient populations with severe VWD (53%-78% of patients with Type 3 VWD), as well as real-world data. [14][15][16] In a pivotal study, on-demand treatment with a single infusion of rVWF given with recombinant FVIII (rFVIII) was effective in 82% of bleeds in 22 patients with severe VWD, with bleed control rated as good or excellent in 100% of bleeds. 14 In the phase 3 surgery study (N = 15), rVWF (with concomitant rFVIII in 11% of bleeds) was associated with overall and intra-operative hemostatic efficacy ratings of good or excellent in all patients with severe VWD.…”

“…15 Overall clinical efficacy for rVWF was also rated as excellent or good in 97% of surgeries (n = 63) in patients with VWD included in a retrospective analysis. 16…”

“…Importantly, rVWF did not result in any treatment-emergent adverse events (including hypersensitivity, thrombotic events, VWF inhibitor development, and transfusion-related infections) in a real-world population, consistent with the safety profile of rVWF demonstrated in clinical trials and a retrospective analysis of rVWF use in surgical procedures. 14–16 In this chart review, among patients receiving initial rVWF therapy at index, 10/11, 31/34, and 49/54 patients received rVWF therapy without FVIII for the treatment of spontaneous/traumatic bleeds, prophylaxis in preparation for surgery, or peri-operative management (on or after the day of surgery), respectively. Administration of rVWF without FVIII in these patients potentially reduced the risk of thromboembolic events, which although rare have been reported in patients with VWD, elevated FVIII levels, and risk factors for thrombosis.…”

Guideline for laboratory diagnosis and monitoring of von Willebrand disease: A joint guideline from the United Kingdom Haemophilia Centre Doctors' Organisation and the British Society for Haematology

“…There is a relative paucity of data on the use of VWF:GPIbR or VWF:GPIbM assays in monitoring of VWF concentrate treatment. 148,149 Field studies should be performed and published on VWF concentrates, but until more conclusive data are available, laboratories should consider performing local verification using either VWF:GPIbR or VWF:GPIbM if these assays are to be used. However, the assays have been well described in measuring VWF activity, 59 and the ability to measure VWF activity rapidly and accurately supports their use as functional measurement in monitoring VWF concentrate infusions.…”