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


CONCLUSIONS
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.
Blood Research Institute and Departments of Pediatrics and Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
T
T
Abshire
Pediatric Hematology, Medical College of Wisconsin, Comprehensive Center for Bleeding Disorders, BloodCenter of Wisconsin, Milwaukee, WI, USA.
J
J
Cox-Gill
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA.|Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
C L
CL
Kempton
Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
F W G
FW
Leebeek
Department of Paediatrics, Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
M
M
Carcao
Department of Medicine, Rochester General Hospital, Rochester, NY, USA.
P
P
Kouides
Department of Biostatistics, Rho, Inc., Chapel Hill, NC, USA.
S
S
Donfield
Malmö Centre for Thrombosis and Haemostasis, Skåne University Hospital, Lund University, Malmö, Sweden.
E
E
Berntorp
D016063:Blood Loss, Surgical / Q000517:prevention & control; D001803:Blood Transfusion; D002986:Clinical Trials as Topic; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000627:therapeutic use; D005260:Female; D006395:Hemarthrosis / Q000209:etiology / Q000517:prevention & control; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008595:Menorrhagia / Q000209:etiology / Q000517:prevention & control; D015337:Multicenter Studies as Topic; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D014842:von Willebrand Diseases / Q000150:complications* / Q000188:drug therapy; D014841:von Willebrand Factor / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014841:von Willebrand Factor; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin
epistaxis; gastrointestinal hemorrhage; hemarthrosis; prophylaxis; von Willebrand disease