Long-Term Prophylaxis in Patients with Von Willebrand Disease and Recurrent Bleeding in Italy

INTRODUCTION: Von Willebrand disease (VWD) is a congenital bleeding disorder caused by Von Willebrand factor (VWF) deficiency or abnormalities. Apart from administration of desmopressin in mild-moderate cases, replacement therapy with VWF/Factor VIII (FVIII) concentrates is the therapy of choice for short-term prophylaxis (STP) during surgery or clinical interventions and it is the conventional approach for Long-Term Prophylaxis (LTP) in patients with severe bleeding tendency. However, LTP with FVIII/VWF concentrates is not always effective and in some cases. Repeated infusions of FVIII/VWF concentrates may increase the risk of thromboembolic events due to FVIII:C overload.

The aim of this analysis was to evaluate the effectiveness of LTP with a VWF concentrate almost devoid of FVIII:C ( vWF conc.) vs VWF/FVIII concentrate in VWD patients with a heavy bleeding phenotype.

METHODS: A retrospective analysis on four VWD patients [type 3 (n= 1), type 2M (n= 1) and type 1 (n= 2)] was carried out in two Italian Hemophilia Centers. These Centers have clinical experience with VWD patients with severe bleeding tendency, on LTP, who switched from VWF/FVIII concentrates to vWF conc. in order to obtain a better control of the bleedings. The patients were included in the analysis if they fulfilled the following criteria: periodical bleeding episodes and previous prophylaxis with VWF/FVIII concentrates. The patients had been previously treated with VWF/FVIII concentrates (prophylaxis: 35-50 IU/Kg/3 times per week; bleeding episodes: 30-50 IU/Kg/day as long as needed), before starting prophylaxis with vWF conc. (prophylaxis: 30-50 IU/Kg/2 times per week and in one case 30 IU/Kg/3 times per week; bleeding episodes: 30-50 IU/Kg/day as long as needed). Data on number of bleeding episodes and hospital admittances, hemoglobin, FVIII:C levels, and number of transfusions were collected. Data after 1 year’s prophylaxis with vWF conc. were compared with those after 1 year’s prophylaxis with VWF/FVIII concentrates.

RESULTS: The number of all bleeding episodes decreased by 96% (mean 14 to 0,5 episodes) and all patients showed a consistent reduction of their own bleeding frequency. Hemoglobin and FVIII:C levels respectively increased by a mean of 2,8 gr/dl (from 8,05 gr/dl to 10,85 gr/dl) and 40% (from 17% to 57%) after LTP with vWF conc. The patient transfusion requirements (number of packed red blood cell concentrate-PRBC) dropped from a mean of 3.5 to zero, and the number of ordinary hospitalizations and day hospital admittances decreased by 100% after LTP with vWF conc. (mean of 15 to 0).

CONCLUSIONS: Our analysis suggests that LTP with a VWF concentrate almost devoid of FVIII is effective and well tolerated highly beneficial for patients both in terms of reduction of bleeding episodes and reduction of number of days spent in hospital with an obvious improvement of the quality of life. A collection of clinical data from a larger population of patients is required to confirm and support these results.