Concordance of DDAVP Response in Siblings with Von Willebrand Disease or Hemophilia a

Background: Von Willebrand disease (VWD) is the most common congenital bleeding disorder, affecting 1 in 5,000 individuals. Von Willebrand factor (VWF) is an important component in platelet binding to form a primary hemostatic plug. Individuals with VWD have difficulty forming a platelet plug and thus have symptoms such as spontaneous bleeding from mucous membranes, epistaxis, excessive bleeding from wounds, and menorrhagia. DDAVP is a synthetic derivative of the antidiuretic hormone, vasopressin, and is currently used as a mainstay of therapy in VWD. The mechanism of action is thought to be a release of VWF from endothelial cell Weibel-Palade bodies through DDAVP's agonist effect on vasopressin V2 receptors, which, in effect increases plasma concentrations of VWF. Not every patient will respond to treatment, so DDAVP challenge tests are recommended in children with newly diagnosed VWD to identify responders in whom DDAVP may be used for the prevention or treatment of bleeding. Von Willebrand disease is inherited in an autosomal dominant pattern, so multiple members are commonly affected within a family. Siblings are likely to carry the same mutation and may or may not have a similar response to treatment. Our study is aimed at addressing the question of whether siblings of responders or non-responders in DDAVP trials have concordant results and therefore do not need DDAVP trial. Methods: With Human Investigation Committee and IRB approval we performed a retrospective chart review of patients who have undergone DDAVP trial at Children's Hospital of Michigan. Levels of VWF were measured at baseline and then at one, two and four hours. A positive response was defined as an increase in VWF of twofold over baseline, to at least 50 IU/dL. Results were then compared among sibling pairs to see if there was a similar response. Results: We examined 57 patients and had 2 related pairs. Before administering DDAVP, the average baseline of VWF activity, VWF antigen, and Factor VIII were 62.71, 60.95, and 73.58 respectively. 55 patients showed full response to trial with DDAVP. In each of our 2 sibling pairs, both family members showed full response. Discussion: Performing DDAVP trials in every child with symptomatic bleeding is not only costly, but also time consuming. In addition, the IV line placements, infusions, and blood draws involved can be a stressful and painful experience for the child. In a study by Archer et al, later published in BJH (2015), they tested response to DDAVP trial in children with low VWF, and had a 95% response rate. They concluded that, given the high response rate, the use of DDAVP challenge tests in pediatric patients with low VWF should be reduced. Conclusion: In our study, we found that in both sets of siblings, each member showed full response to trial with DDAVP. If there is a genetic correlation to whether or not one responds, these siblings may have benefited from not having to each undergo testing. We would like to further our investigation with a larger data set, and plan to look at a large multicenter cohort. Additionally, although not a primary endpoint of our study our data confirm the findings from the study by Archer et. al.. All of our patients with low VWF activity (>30%<50%) responded to DDAVP and DDAVP trials may not be needed in this group. Disclosures No relevant conflicts of interest to declare.