Effectiveness of DDAVP in Von Willebrand’s Disease.

Objective: Of the inherited bleeding disorders von Willebrand’s disease (VWD) is the most common, with a prevalence of one in 10,000. Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]) and a variety of plasma-derived concentrates of Factor VIII (FVIII) and von Willebrand factor (VWF) have been used to treat VWD. A prospective multicenter European study recently reported the effectiveness of DDAVP to be 27% in type 1 VWD and 18% in all type 2, which suggests that DDAVP is less effective than previously thought. Here we report our experience in a retrospective analysis of patients with known VWD challenged with DDAVP.

Methods: Intranasal DDAVP was administered to 20 patients with known VWD who were studied before and 2 hours after dosing. A response to DDAVP was defined by a 2-fold increase in both FVIII concentration and ristocetin cofactor activity (VWF:RCo) as well as attainment of a level of at least 30 IU/dL. In addition, 6 subjects had bleeding time (BT) tests performed. Statistical analysis was performed using one-tailed multivariate Student’s t-test.

Results: Three of the 20 patients were excluded from the study: 2 had acquired VWD and 1 inadequate data. Of the 17 evaluable patients, 13 were type 1 and four type 2 (confirmed by multimer analyses). Overall response in the 17 patients was 59% (p<0.001); 13 subjects had FVIII levels that increased to more than 80 IU/dl, and 9 subjects had VWF:RCo levels of more than 50 IU/dl. Responses were observed in 8 of the 13 (62%, p<0.001) subjects with type 1 disorder and 2 of the 4 with type 2. The BT was >10 min prior to DDAVP and decreased significantly, to ≤7.5 min, in 5 of the 6 patients after DDAVP. Even when more stringent requirements for defining a response were used (a 3 fold increase and a level of at least 30 IU/dL of both FVIII and VWF:RCo activity, as used by the European multicenter study), 5 of 13 (39%, p=0.01) of the type 1 patients had a response. The average increase in responders in VWF:RCo was 3.33 fold and FVIII, 4.43 fold.

Conclusions: The majority of patients with VWD have a significant biological response to intranasal DDAVP; a challenge test with intranasal drug identifies responders who should be considered for treatment with this agent.