T Abshire1, J Cox-Gill2, C L Kempton3,4, F W G Leebeek5, M Carcao6, P Kouides7, S Donfield8, E Berntorp9. 1. Blood Research Institute and Departments of Pediatrics and Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. 2. Pediatric Hematology, Medical College of Wisconsin, Comprehensive Center for Bleeding Disorders, BloodCenter of Wisconsin, Milwaukee, WI, USA. 3. Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA. 4. Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. 5. Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands. 6. Department of Paediatrics, Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada. 7. Department of Medicine, Rochester General Hospital, Rochester, NY, USA. 8. Department of Biostatistics, Rho, Inc., Chapel Hill, NC, USA. 9. Malmö Centre for Thrombosis and Haemostasis, Skåne University Hospital, Lund University, Malmö, Sweden.
Abstract
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: -51.6 to -1.7), and the median annualized bleeding rate was even lower (4.0; 95% confidence interval: -57.5 to -5.3) 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.
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: -51.6 to -1.7), and the median annualized bleeding rate was even lower (4.0; 95% confidence interval: -57.5 to -5.3) 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.
Authors: Nathan T Connell; Veronica H Flood; Romina Brignardello-Petersen; Rezan Abdul-Kadir; Alice Arapshian; Susie Couper; Jean M Grow; Peter Kouides; Michael Laffan; Michelle Lavin; Frank W G Leebeek; Sarah H O'Brien; Margareth C Ozelo; Alberto Tosetto; Angela C Weyand; Paula D James; Mohamad A Kalot; Nedaa Husainat; Reem A Mustafa Journal: Blood Adv Date: 2021-01-12