Safety and efficacy of a high-purity plasma-derived von Willebrand Factor in patients with von Willebrand disease (VWD) undergoing prophylaxis for gastrointestinal bleeding: results from a post-marketing study

Objective Although prophylaxis is generally accepted as an effective method to prevent bleeding events, little is known about the dosing and the outcome of prophylactic treatment in patients with VWD who experienced recurrent gastrointestinal (GI) bleeding. The objective was to evaluate the safety and efficacy of a plasmatic Factor VIII-poor von Willebrand Factor (pdVWF) concentrate (Wilfactin®/Willfact® - LFB) in routine clinical use.

Material and Methods Patients suffering from all types of VWD undergoing prophylaxis for GI bleeding were enrolled in the prospective non-interventional post-marketing study conducted in 31 centres in France.The frequency of breakthrough bleeding, treatment dosing and tolerability in prophylactic treatment setting for GI bleeding were evaluated.

Results 13 patients (4 type 3 and 9 type 2) who entered or continue prophylaxis for GI bleeding were analysed. All had basal VWF:RCo ≤15 IU/dL. Among them, 8 (62 %) male and 5 (38 %) female. Median age was 57 years (range 33–81 years; 31 % being 65 or older). Most patients had VWD associated angiodysplasia. Patients infused pdVWF concentrate at home (45.2 IU/kg (22 to 55) one to three times per week (median 2.5) for 6.7 to 43.4 months (median 37.1). A total of 4036 infusions were given. Breakthrough bleeds (spontaneous or post-traumatic, GI or other bleeds requiring additional treatment with pdVWF) occurred following 1.4 % prophylactic infusions. During routine prophylaxis, 5 (38 %) patients did not experience any bleeding event within 3 days of administration of concentrate. Overall, the median annual bleeding rate (ABR) in 10 patients treated prophylactically for at least one year was 1.1 (range 0.0-11.0). The highest ABR was due to the recurrence of GI bleedings in one patient with type 2A and multiple angiodysplasia of small intestine (17 events in 18.6 months). There were no notable differences in the frequency of bleeding events when stratified by age or phenotype. During a prolonged exposure, the pdVWF was well tolerated without report of thrombotic events, neutralising VWF inhibitors or any other related serious adverse events.

Conclusion In this study, routine prophylaxis with pdVWF was well tolerated and contributed to an effective management of recurrent GI bleeding.

Publication History

Article published online:
18 June 2021