High Dose Intranasal Desmopressin (DDAVP) Therapy in Type 2M Von Willebrand Disease (VWD): A Prospective Open Label Trial.

DDAVP is effective treatment for VWD patients with adequate biologic response to administration of a trial dose. Intranasal therapy offers the advantage of ease of administration. Few prospective data evaluating response to intranasal DDAVP exist, especially in less common types such as type 2M VWD. As part of a study of a large Amish kindred of VWD in Northern Indiana, we conducted a prospective open label trial to assess response rate to a single dose of high concentration intranasal DDAVP in 11 affected individuals. Stimate® Nasal Spray (1.5 mg/ml) with weight based dosing was used. Laboratory parameters obtained prior to and 90 minutes after administration of Stimate® to assess for response included ristocetin cofactor activity (VWF:RCo), factor VIII activity(VIII:C), and VWF antigen (VWF:Ag) values. VWF:RCo ≥ 40% at 90 minutes post Stimate® administration was defined as adequate response. Of 212 evaluated members, 54 affected members were identified as defined by abnormally low VWF levels (VWF:RCo levels <35%) and confirmed by presence of C-to-T transition at nucleotide 4120 in exon 28 of the VWF gene. Multimer analysis in a subset of the affected individuals showed a normal pattern. Eleven adult Amish patients (5 males, 6 females), ranging in age from 20 to 56 years, were enrolled. Baseline VWF:RCo values ranged from 10% to 14%. Ten patients reported no active bleeding symptoms at the time of initiation of the trial, while one had ongoing problems with gingival bleeding. All patients weighed >50 kg; hence two intranasal Stimate® spray puffs were administered to each patient. Five of eleven patients had response to intranasal DDAVP as evidenced by ≥ 40% VWF:RCo levels 90 minutes after receiving Stimate® (Response range: 4.0 fold to 4.86 fold rise). The remaining patients did not meet definition of response (Response range: 1.6 fold to 3.8 fold rise). There were no major adverse effects. Nine patients had mild facial flushing alone; one patient had flushing and headache; one patient was asymptomatic. After Stimate® administration, the patient with gingival bleeding reported complete cessation of bleeding sustained for 24 hours. This is the first and largest report to date assessing response to intranasal DDAVP therapy in 2M VWD patients. High concentration intranasal DDAVP may be used for minor bleeding episodes in those patients with adequate response to a trial dose. It is easily self administered as home based first line hemostatic therapy. Intranasal DDAVP is well tolerated with minimal adverse effects. Prospective clinical correlation of efficacy is underway in this population.