Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy

Abstract

Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed in severe haemophilia A, may also be observed. The bleeding patterns of VWD can affect quality of life, and may be life-threatening. The von Willebrand Disease Prophylaxis Network is an international study group formed with the goal of investigating the role of prophylaxis in clinically severe VWD. The objective of the present study is to investigate the response to prophylaxis focusing primarily on epistaxis, joint bleeding, gastrointestinal bleeding, and heavy bleeding associated with menses. Data from 105 subjects, 10 enrolled in a prospective study and 95 in a retrospective study between 2008 and 2013, were available for analysis. The median annualized rate reductions in bleeding were significant for epistaxis (P < 0.0001), gastrointestinal bleeding (P = 0.0003), joint bleeding (P < 0.0001), and menorrhagia (P = 0.008). Doses on a group level were approximately the same prior to and during prophylaxis, but more patients with gastrointestinal bleeding had prophylaxis three or more times per week as well as higher dosages. Our study, which primarily used retrospective data, indicates that prospective studies are needed to better delineate the doses and dose intervals that should be used for prophylactic treatment of VWD.

Bleeding‐related hospitalization in patients with von Willebrand disease and the impact of prophylaxis: Results from national registers in Sweden compared with normal controls and participants in the von Willebrand Disease Prophylaxis Network

“…The von Willebrand Disease Prophylaxis Network (VWD PN) is an international study group formed with the goal of evaluating prophylactic regimens for people with clinically severe VWD. Retrospective and prospective studies from the VWD PN showed that prophylactic treatment of severe forms of VWD is efficacious and a significant overall reduction in haemorrhages occurred after initiation of prophylaxis …”

Von Willebrand Disease in the elderly: clinical perspectives

“…The strategy is similar to hemophilia treatment, where factor concentrates are regularly administered to reduce joint bleeding and its associated long-term morbidity 42,43. Symptomatology in VWD is more variable than hemophilia; joint bleeding is less common and mucosal surface bleeding can be the predominant bleeding pattern 44. Prophylaxis with VWF concentrates significantly reduces mucosal and joint bleeding rates 44–46.…”

“…Symptomatology in VWD is more variable than hemophilia; joint bleeding is less common and mucosal surface bleeding can be the predominant bleeding pattern 44. Prophylaxis with VWF concentrates significantly reduces mucosal and joint bleeding rates 44–46. A recombinant VWF concentrate has also been developed that is effective at stabilizing FVIII47 and controlling bleeding events 48…”

Current controversies in the diagnosis and management of von Willebrand disease

“…What is the optimal dosing regimen? Further research is needed and a prospective trial is ongoing in the VWD PN [Holm et al 2015].…”

“…A recent update of this study reported continued success with a total of 105 patients. A total of 10 of these patients are enrolled in a prospective study to help ascertain the most appropriate dosing regimen using a dose-escalation strategy [Holm et al 2015].…”