Repeated infusions of DDAVP induce low response of FVIII and vWF but not of plasminogen activators.

Although the vasopressin analogue desamino-d-arginine vasopressin (DDAVP) induces a very well characterized increase in factor VIII (FVIII), von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), the mechanism(s) by which DDAVP enhances the plasma levels of these proteins is poorly understood. Some clinical evidence suggests that certain patients repeatedly treated with DDAVP at closely spaced intervals become progressively unresponsive (tachyphylaxis). In order to investigate the effect of repeated DDAVP infusion on the behaviour of FVIII, vWF, t-PA and u-PA, we infused three different doses of DDAVP (0.3 microgram/Kg) to six healthy volunteers (19-26 years old, mean 22) at 12-hour intervals. Blood samples were collected immediately before and after DDAVP. The second and third infusion of DDAVP induced a low response of FVIII and vWF. In contrast, t-PA and u-PA exhibited a consistent response after each DDAVP infusion. If the progressive decrease of FVIII and vFW response observed in healthy subjects after repeated doses of DDAVP at 12-hour intervals is extended to haemophiliacs and von Willebrand's patients, the usefulness of desmopressin may be limited when these proteins must be raised therapeutically for a prolonged period of time. Finally, our results suggest that the mechanism for regulating the release of vWF and plasminogen activators in the conditions of our study are not dependent.