Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP).
The synthetic analog of vasopressin desmopressin (DDAVP) is widely used for the treatment of patients with von Willebrand disease (VWD), hemophilia A, several platelet disorders, and uremic bleeding. DDAVP induces an increase in plasma levels of von Willebrand factor (VWF), coagulation factor VIII (FVIII), and tissue plasminogen activator (t-PA). It also has a vasodilatory action. In spite of its extensive clinical use, its cellular mechanism of action remains incompletely understood. Its effect on VWF and t-PA as well as its vasodilatory effect are likely explained by a direct action on the endothelium, via activation of endothelial vasopressin V2R receptor and cAMP-mediated signaling. This leads to exocytosis from Weibel Palade bodies where both VWF and t-PA are stored, as well as to nitric oxide (NO) production via activation of endothelial NO synthase. The mechanism of action of DDAVP on FVIII plasma levels remains to be elucidated. The hemostatic effect of DDAVP likely involves additional cellular effects that remain to be discovered.
Kaufmann
J E
JE
Division of Clinical Biochemistry, Geneva, Switzerland.
Vischer
U M
UM
D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005169:Factor VIII / Q000187:drug effects / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D006490:Hemostatics; D014841:von Willebrand Factor; D005169:Factor VIII; D010959:Tissue Plasminogen Activator; D003894:Deamino Arginine Vasopressin