Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN)

Abstract

Summary The bleeding patterns of severe von Willebrand's disease (VWD) adversely affect quality of life, and may be life threatening. There is a presumed role for prophylaxis with VWF‐containing concentrates, but data are scarce. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is not responsive to other treatment(s).Using a retrospective design, the effect of prophylaxis was studied. Availability of records to document, or reliably assess, the type and frequency of bleeding episodes prior to, and after, the initiation of prophylaxis was required. Annualized bleeding rates were calculated for the period prior to prophylaxis, during prophylaxis and by primary bleeding indication defined as the site accounting for more than half of all bleeding symptoms. The Wilcoxon signed‐rank test of differences in the medians was used. Sixty‐one subjects from 20 centres in 10 countries were enrolled. Data for 59 were used in the analysis. The median age at onset of prophylaxis was 22.4 years. Type 3 VWD accounted for the largest number (N = 34, 57.6%). Differences in bleeding rates within individuals during compared with before prophylaxis were significant for the total group (P < 0.0001), and for those with primary bleeding indications of epistaxis (P = 0.0005), joint bleeding (P = 0.002) and GI bleeding (P = 0.001). The effect of prophylaxis was similar among those age < 18 years and those ≥18. One person developed an inhibitor during treatment. We conclude that prophylactic treatment of VWD is efficacious.

How I treat type 2 variant forms of von Willebrand disease

“…Prospective trials are needed to evaluate the cost-effectiveness and the improvement on a patient's quality of life of prophylaxis in comparison with on-demand treatment, although clinical experience has been rated as satisfactory. [65][66][67] Antineoangiogenesis drugs (such as thalidomide), atorvastatin, and octreotide could have a role as occasionally reported. 60 Use of selective VWF concentrates (eg, Wilfactin) may be considered for secondary prophylaxis of patients with high basal levels of FVIII, to lower thrombotic risk.…”

Alloantibodies in von Willebrand disease

“…13 With regard to prophylaxis, a recently published retrospective study reports that of 59 severe VWD patients, only 1 developed an inhibitor during the reporting period. 41 In another recent study reporting 32 patients receiving secondary prophylaxis for VWD, 1 developed an inhibitor following intensive exposure for an ankle bleed. 42 As previously mentioned, some patients, particularly those with high-titer anti-VWF antibodies, can experience severe or life-threatening anaphylactic reactions when reexposed to VWF.…”

Principles of care for the diagnosis and treatment of von Willebrand disease

“…Clinical experience with secondary prophylaxis in VWD has been rated as excellent or good in the large majority of case series, despite using different schedules of administration. [47][48][49] However, prospective trials are needed to better evaluate the cost-effectiveness of this approach and the impact on patient's quality of life in comparison with on-demand therapy.…”