DDAVP at a Maximal Dose of 15 ug Administered Subcutaneously Is a Safe and Effective Alternative to 20 ug IV for Patients > 50 kg with von Willebrand Disease or Mild Hemophilia A.

Background: DDAVP (desmopressin) is commonly used for the prophylaxis and treatment of bleeding in patients with mild forms of von Willebrand disease (VWD) and Hemophilia A (HemA). The standard dose is 0.3 ug/kg IV, to a maximum of 20 ug. In 1995, our Bleeding Disorders Program began to use a maximum dose of 15 ug both for DDAVP challenges and for therapeutic purposes. This dosing change was triggered by the new availability of 15 ug (1 ml) vials of DDAVP. We also switched to subcutaneous administration rather than intravenous, given the smaller volume (1 ml), and the body of evidence supporting this route of administration (

Method: In order to evaluate this new dosing regimen, a retrospective review was performed of 62 patients with VWD (n=36) or mild hemophilia (n=26) weighing ≥ 50kg who underwent DDAVP challenges using a 15 ug s/c dose of DDAVP. Data was also collected on the 9 patients (5 VWD, 4 HemA) tested prior to 1995 who received 20 ug IV of DDAVP.

Results: Levels of von Willebrand factor antigen (vWFag), ristocetin cofactor activity (RCof) and factor VIII (FVIII) were measured immediately prior to and 1 hour after administration of DDAVP. In the VWD patients (14M, 22F), median baseline levels of vWFag, RCof and FVIII were 31, 27 and 45 U/ml respectively, and rose to a median of 93, 90 and 177 U/ml following a 15 ug dose of DDAVP. This resulted in a median increase of 64 for vWFag (range 0–180), 55 for RCof (24–191) and 121 for FVIII (21–237). Results were comparable in the 5 pts who received 20 ug doses of DDAVP, achieving median increases of 77 (range 17–125), 53 (40–91) and 98 (79–184) respectively. In the HemA patients (19M, 7F), median baseline level of FVIII was 23 U/ml, and rose to a median of 57 U/ml following 15 ug DDAVP. Median increase in FVIII levels was 33 U/ml (range 2–108). These results compare favorably to the 4 patients who received 20 ug DDAVP and achieved a median FVIII increase of 19 U/ml (range 9–60). Chart review identified 26 patients (14 VWD, 12 HemA) who successfully received 15 ug doses of DDAVP in 44 clinical settings, either for the treatment of an acute bleeding episode or as prophylaxis prior to a planned surgical or dental procedure.

Conclusions: DDAVP given subcutaneously to a maximum dose of 15 ug appears to be a safe and effective alternative to 20 ug IV for pts > 50 kg with VWD or mild hemophilia A.