Secondary long-term prophylaxis in von Willebrand disease: an Italian cohort study

Patients with severe forms of von Willebrand's disease (VWD) may have frequent episodes of mucocutaneous bleeding and also of hemarthrosis or hematomas. However, little retrospective or prospective data on secondary long term prophylaxis in VWD are available. Aim of this study was to evaluate the efficacy and safety of fixed regimens of prophylaxis with factor VIII/VWF concentrates in our cohort of VWD patients with recurrent joint and gastrointestinal (GI) bleeds. This is a cohort study on 452 VWD patients enrolled in our database until December 2004. 89/452 cases (20%) were treated with FVIII/VWF concentrates during the last two years because of one or more bleedings and 11/89 (12%) were included in a long term prophylaxis program because of frequent recurrence of bleeds at the same sites. Patients were given 40 FVIII IU/Kg of high- (Alphanate, Fanhdi) or intermediate-purity (Haemate-P) concentrates, two-three times a week to maintain FVIII and VWF levels higher than baseline during prophylaxis. Effectiveness of prophylaxis was based on resolution/ reduction of bleeding as well as on numbers of packed red blood cells and days of hospitalization. Safety was measured by monitoring side effects and FVIII levels before and after every injection during the first three weeks of prophylaxis. All the 11 patients were severe with VWF:RCo baseline levels below 10 U/dL. Prophylaxis was started because of GI bleeds in 7 patients with VWD type 3 (n=1), 2A (n=4), 2M (n=1) and 1 (n=1) and for joint bleeding only in VWD type 3 (n=4). Prophylaxis could stop bleeding in 8 patients and largely reduced hospitalization for blood transfusions in the remaining 3. FVIII levels were always below 180 U/dL in all VWD and no side effects, including thrombosis, were observed. Secondary long-term prophylaxis by high-and intermediate purity FVIII/VWF concentrates is effective and safe in severe forms of VWD. Cost-effectiveness of these prophylaxis regimens versus on demand therapy should be investigated in large prospective studies.