Response of factor VIII/von Willebrand factor to DDAVP in healthy subjects and patients with haemophilia A and von Willebrand's disease

Abstract

These studies were designed with the purpose of providing clinico-pharmacological information relevant to the use of DDAVP in the management of mild haemophilia and von Willebrand's disease (VWD). In healthy subjects, intravenous DDAVP produced its maximal response at a dose of 0.3 micrograms/kg. The extent of the increase in factor VIII coagulant activity (VIII:C) and factor VIII related antigen (VIIIR:Ag) induced by this dose was not significantly different from that observed with the same dose in haemophiliacs and VWD patients. In these, the bleeding time was not shortened. DDAVP given intranasally was followed by a two-fold increase of VIII:C. This route of administration might be adopted to provide an emergency aid in bleeding patients and to yield higher VIII:C levels in blood donors. In healthy subjects, the half-disappearance time of autologous VIII:C after increase induced by i.v. DDAVP is similar to that observed in patients with VWD treated in the same conditions, whereas the response appears to be more prolonged in haemophiliacs. This study shows that the consistency of the VIII:C response tends to decrease when repeated doses are given to healthy subjects. Repeatedly-treated haemophiliacs and VWD patients showed varied patterns, ranging from no change of the response to its early abolishment.