Prophylaxis escalation in severe von Willebrand disease: a prospective study from the von Willebrand Disease Prophylaxis Network

Abstract

Summary. Background: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may require von Willebrand factor (VWF) replacement therapy. There are little data on the use of prophylaxis in VWD, and none have been applied in a prospective, treatment escalation design. Objective: Evaluate the effect of escalating dose prophylaxis in severe VWD. Methods: Patients eligible for enrollment in this prospective study included those with type 1 VWD with VW factor activity-ristocetin cofactor ratio ≤ 20% and unresponsive to desmopressin, patients with type 2 VWD not responsive to desmopressin and all subjects with type 2B and type 3 VWD. Entry criteria were strictly defined, as were therapy escalation parameters and clinical data collection. Results: Eleven subjects completed the study. Six had type 2A, and five had type 3 VWD. Six patients presented with epistaxis, three with GI bleeding, and two with joint bleeding. Seven had dose escalation above the first level. Among the 10 subjects with evaluable bleeding log data, use of prophylaxis decreased the median annualized bleeding rate from 25 to 6.1 (95% confidence interval of the rate difference: À51.6 to À1.7), and the median annualized bleeding rate was even lower (4.0; 95% confidence interval: À57.5 to À5.3) when the subjects reached their final dosing level. Conclusion: This is the first prospective study to demonstrate that prophylaxis with VW factor concentrates is highly effective in reducing mucosal and joint bleeding rates in clinically severe 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

“…In the second segment of this study, subjects were enrolled in prospective or retrospective studies as detailed in . The VWD PN studies are designed and supervised by an international network (see Appendix ).…”

“…In the second segment of this study, subjects were enrolled in prospective or retrospective studies as detailed in. 3,4,6 The VWD PN studies are designed and supervised by an international network (see Appendix S1). The objectives were to describe demographics of the use of prophylaxis in VWD and to develop evidencebased guidelines for prophylaxis in VWD.…”

“…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 …”

“…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. [3][4][5][6] Hospitalization due to bleeding in patients with VWD is demanding for both the individuals and the healthcare system-being hospitalized is stressful and affects quality of life for patients and is costly for society. Therefore, prophylactic treatment in VWD constitutes an approach which addresses both problems.…”

Von Willebrand Disease in the elderly: clinical perspectives

“…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…”