Comparing the Desmopressin (DDAVP) Challenge Test to DDAVP Clinical Response in Pediatric Patients with Von Willebrand's Disease: A Single Center Experience

Introduction

Von Willebrand's disease (VWD) is the most common inherited bleeding disorder. It is characterized by both quantitative and qualitative defects of the von Willebrand Factor (VWF) and generally manifests as menorrhagia, epistaxis and easy bruising. Initial treatment involves the use of desmopressin (DDAVP) that induces the release of VWF from the endothelium. Patients undergo a DDAVP challenge test that involves intravenous DDAVP (IV-DDAVP) infusion with multiple blood draws to determine an increase in the VWD panel. Due to the DDAVP challenge test being a costly and lengthy process, we sought to evaluate the prognostic utility of the challenge test in patients who responded favorably.

Methods

A retrospective cohort study was conducted in pediatric patients aged 18 years or younger with a laboratory diagnosis of VWD who underwent the DDAVP challenge test between 2005 and 2015 at our institution. VWD panel results pre and post DDAVP challenge test were obtained from clinical records. A complete response was defined as a 2-fold increase at 1-3 hours or at least 1.5-fold increase at 4-6 hours post-infusion. Patients' clinical records were reviewed for initial presentation and response to DDAVP. SPSS version 23.0.0 was used to analyze demographic and laboratory data, with frequencies and paired t-tests performed for comparison where appropriate.

Results

Seventy two pediatric patients were identified with a diagnosis of VWD: 34 (47%) were VW type 1, 51 (72%) were females and 50 (69%) were Caucasian. Challenge results were available for 48 patients (66%): Post-DDAVP levels were significantly higher than baseline (p = <0.001) in the VWD panel for either times (1-3 or 4-6 hours). Thirty-seven patients (51%) had both challenge results and clinical symptoms reported with 78% (29/37) considered responders and 22% (8/37) considered non-responders to IV-DDAVP. 86% (25/29) of responders were initially placed on intranasal DDAVP (IN-DDAVP) alone while the others received combined therapy with addition of a plasma derived product (PDP). All non-responders initially received DDAVP therapy with some improvement in their clinical symptoms. Eleven (38% of responders) and four (50% of non-responders) were switched to a PDP, mostly for better symptom control. Six responders (16%) had side-effects with DDAVP.

Conclusion

A high proportion of our patients with VWD responded to the DDAVP challenge test, but subsequently required therapy with a PDP; and half of non-responders were able to use DDAVP. In our pediatric patient population, an initial IV-DDAVP challenge test did not identify those that would respond clinically to IN-DDAVP therapy long-term. Thus, more studies addressing the utility of the challenge test in VWD would be needed before drawing further conclusions on its prognostic value.