Laboratory Response to Desmopressin in Children with Von Willebrand Disease: Results of a Multicenter Survey

Background: Desmopressin (DDAVP, 1-deamino-8-D-arginin vasopressin) as synthetic analogue of the pituitary hormone vasopressin affects hemostasis by the release of von Willebrand factor (VWF) and coagulation factor VIII from endothelium. The necessity of DDAVP testing prior to the first therapeutic use is a matter of controversial discussion. Aim of this retrospective study was to evaluate the results of DDAVP testing in children with von Willebrand disease (VWD) in seven pediatric hemostaseologic centers.

Patients and Methods: Data from DDAVP tests carried out between 2000 to 2007 were included and obtained using a standardised protocol by personel visits of the centers. DDAVP response criteria matched with those of a recently published multicenter study (Castaman et al., Blood 2008, 3531-9). Complete response to DDAVP after administration was defined as an increase in von Willebrand factor antigen (VWF:Ag), collagen-binding activity (VWF:CB) or ristocetin cofactor activity (VWF:RCo) and factor VIII procoagulant activity (FVIII:C) to 50% or higher. In partial responders VWF:Ag, VWF:CB/VWF:RCo or FVIII:C were lower than 50% but increased at least 3-fold from baseline while in non-responders neither of the before-mentioned criteria were fulfilled. Patients with VWF:Ag, VWF:CB/VWF:RCo or FVIII:C of 50% or higher at time of testing before DDAVP infusion were considered as complete responders if a level of 100% or higher were reached for all parameters. Data from 114 children (each 57 boys and girls, median age: 6.2 years, range: 1.4 to 17.8 years) were evaluated. In 99 patients DDAVP was given intravenously at a dosage ranging from 0.25 to 0.41 μg/kg (mean: 0.32 μg/kg) and in 15 intranasaly at an absolute dosage of 40 to 300 μg. The times for determination of the coagulation parameters after DDAVP infusion varied among the centers and ranged from 30 min to 12 hours.

Results: The VWD of type 1 was present in 98 children. Before DDAVP administration the VWF:Ag ranged from 11% to 77% (mean: 51%), VWF:CB from 7% to 99% (mean: 46%), VWF:RCo from 15% to 97% (mean: 53%) and FVIII:C from 27% to 116% (mean: 67%). A complete response was detected in 84 children (86%), a partial response in ten (10%) and a non-response in four (4%) patients. Twelve patients suffered from VWD of type 2A. The range of baseline values was as follows: VWF:Ag 8% to 66% (mean: 34%), VWF:CB 9% to 48% (mean: 25%), VWF:RCo from 5% to 71% (mean: 26%) and FVIII:C from 19% to 90% (mean: 51%). A complete response was observed in five children (42%), a partial response in four (33%) and a non-response in three (25%) patients. In the two patients with VWD of type 2M one showed a complete and the other one a partial response. In both children with VWD of type 2N a complete response was detected. DDAVP side effects were observed only in two out of 114 patients (1.8%) who suffered from nausea, vomiting, headaches and fatigue.

Conclusion: DDAVP testing prior to therapeutic administration is recommended to determine its efficiency and the individual response on hemostasis. The non-response in seven (6%) and the partial reponse in 15 (13%) out of a total cohort of 114 children with VWD underlines the necessity of this recommendation in pediatrics. However, a standardisation of the test procedure is needed.