Secondary long-term prophylaxis may lead to decreased bleeding risk and incidence in patients with severe von Willebrand disease compared with on-demand treatment, the current standard of care, according to a study published in Blood Transfusion.
Researchers enrolled 22 patients with severe inherited von Willebrand disease, 19 of whom were randomly assigned to receive either on-demand treatment (9 patients) or prophylaxis (10 patients) with von Willebrand factor (vWF)/factor VIII (FVIII) concentrates. Twelve patients completed the full study. Patients in the on-demand treatment cohort received 40 to 60 IU vWF:RCo/kg body weight at the onset of each bleeding episode, while patients in the prophylaxis cohort received 60 IU vWF:RCo/kg body weight once every 2 or 3 days.
Efficacy endpoints included proportion of patients who did not experience bleeding episodes, incidence and duration of bleeding episodes, and mean dose of vWF/FVIII concentrate administered per bleeding episode. Safety endpoints included number of adverse and thrombotic events.
During the study, 100% of patients in the on-demand treatment cohort and 60% of patients in the prophylaxis cohort experienced at least 1 bleeding episode. Patients receiving on-demand treatment experienced a significantly higher number of total bleeds compared with patients receiving prophylaxis (172 vs 32; P <.0001), though 112 of the bleeds in the on-demand treatment group occurred in a single patient. However, the authors noted that even after excluding the patient in the on-demand treatment cohort who experienced 112 bleeds, “the number of bleeding episodes in the on-demand treatment group was still 2-fold higher” compared with the prophylaxis group.
Additionally, bleeding risk was lower in the prophylaxis cohort, with an estimated relative attributable risk of -0.667 (P <.001).
Adverse events were reported by 3 patients receiving on-demand treatment and 6 patients receiving prophylaxis. Adverse events occurred primarily through blood and lymphatic system disorders. None of the observed adverse events were determined to be associated with the study medication.
The authors acknowledged the low sample size and resulting heterogeneity in baseline characteristics as limitations of their study. However, they noted that “other key parameters were similar between groups, hence supporting the consistency of the study comparisons.” They concluded that prophylactic use of vWF/FVIII concentrate may lead to decreased bleeding risk and frequency, but further studies with larger cohorts are warranted.
1. Peyvandi F, Castaman G, Gresele P, et al. A phase III study comparing secondary long-term prophylaxis versus on-demand treatment with vWF/FVIII concentrates in severe inherited von Willebrand disease [published online February 4, 2019]. Blood Transfus. doi: 10.2450/2019.0183-18