DESMOPRESSIN STIMULATES THE EXPRESSION OF P-SELECTIN ON HUMAN PLATELETS IN-VITRO

Desmopressin (1-desamino-8-D-arginine vasopressin (DDAVP)) is a synthe tic analog of arginine vasopressin (AVP) and is useful in the treatmen t of some bleeding disorders. The mechanism of improved hemostasis in patients with platelet dysfunction is uncertain. Platelet-rich plasma samples from 35 normal subjects were incubated with serial dilutions o f DDAVP, AVP, and adenosine diphosphate. The expression of the platele t activation-dependent antigen CD62 (P-selectin) was measured by fluor escent-labeled monoclonal antibody and flow cytometry. DDAVP at concen trations of 1.0 to 1000 nmol/L stimulated significant expression of CD 62 on normal platelets in vitro. At a pharmacologic concentration of D DAVP (1 nmol/L), 14.1% (0.6% to 45.4%) (median and range) of platelets expressed CD62. There was a strong correlation between DDAVP-induced and AVP-induced CD62 expression (r(s) = 0.62, p = 0.0008) but not betw een DDAVP-induced and ADP-induced expression, suggesting a V-1 recepto r-mediated mechanism. Preincubation of platelets with a vasopressin V- 1 receptor antagonist completely inhibited CD62 expression in response to DDAVP. We conclude that DDAVP directly activates platelets by inte raction with the platelet V-1 receptor in vitro. This finding may part ially explain in vivo effects of DDAVP on hemostasis.