A Prospective Comparision of Intranasal (I.N.) and Subcutaneous (S.C.) Desmopressin (DDAVP) Therapy in Type 2M Von Willebrand Disease (VWD).

DDAVP is effective therapy for VWD patients with documented adequate biologic response. Few data evaluating DDAVP exist in the less common type 2M VWD Seventy one members of an Amish kindred diagnosed with type 2 M VWD with abnormal VWF:Rco <35% and C-to-T transition at nucleotide 4120 in exon 28 of the VWF gene have been identified; 11 previously participated in an evaluation of weight-based trial dose of I.N. DDAVP(Stimate® Nasal Spray: 1.5 mg/ml concentration, 2 puffs weight >50 kg); 9/11 were further evaluated for response to S.C. DDAVP (0.3 microgram/kg). These 9 patients included 5 males, 4 females; age range: 21 to 58 years; weight range: 59–101.8 kg. Response utilizing ristocetin cofactor activity (VWF:Rco), factor VIII activity (VIII:C), and VWF antigen (VWF:Ag). Was assessed at 90 minutes post Stimate® administration and at 60 and 120 minutes post S.C. administration; values were also obtained at 4 and 6 hours post S.C. DDAVP to assess pharmacokinetics. Response to DDAVP was defined as VWF:Rco >40%. Five people (55%) responded to Stimate®; three (33%) responded to S.C. DDAVP. There were no major adverse effects. Two males who had responded to I.N. route did not respond to S.C. route; one female who responded to S.C. DDAVP did not respond to Stimate®. Responses fell below 40% at 4 and 6 hours post-dose. Responses to DDAVP are thus observed in a subset of individuals with type 2M VWD. Although all individuals tested exhibit the 4120C>T mutation, the response to DDAVP as measured by VWF: Rco levels varied from 1.7 to 4.9 fold. Therefore response to DDAVP in these patients appears not to be solely based upon the mutation causing the VWD phenotype but may be modified by other environmental and genetic factors. DDAVP responsiveness is an interesting phenotypic trait to be studied. Response may vary based on route of administration; this report highlights the necessity of assessing response to a trial dose by the intended route of administration prior to clinical use. Both I.N. and S.C. DDAVP may be used for minor bleeding episodes in those patients with type 2M VWD with adequate response to a trial dose. Both may be self administered as home based first line hemostatic therapy and are well tolerated.