Response of neonatal platelets to nitric oxide in vitro

Objectives:Several studies have demonstrated altered platelet function duri ng nitric oxide inhalation (iNO) in adults and neonates. In vitro NO inhibi ts activation of fibrinogen receptor glycoprotein (GP) IIb/IIIa in a dose-d ependent manner. In neonates GPIIb/IIIa response to stimulation is physiolo gically attenuated during the first days after birth in comparison to adult s; the effects of NO on GPIIb/IIIa in neonates, however, are less establish ed. We investigated the response of platelets from neonates, their mothers, and nonpregnant controls to the NO donor SIN-1 in vitro. Design: Umbilical cord and venous (mother, controls) platelet-rich plasma w as stimulated in vitro with 10 muM ADP or 0.05 U/ml thrombin in the presenc e or absence of 10 muM SIN-1. GPIIb/IIIa activation was determined by two-c olor flow cytometry. Setting: Delivery department of an university hospital. Patients and participants: Ten healthy term neonates, their mothers and non pregnant controls. Measurements and results: NO significantly reduced GPIIb/IIIa activation in thrombin- and ADP-stimulated platelets in all groups (p < 0.001). Neonatal platelets were significantly hyporeactive to stimulation (p < 0.05), but t he relative response to SIN-1 was similar in all three groups (70 +/- 5%). Conclusions: The relative amount of NO-induced inhibition of GPIIb/ IIIa ac tivation in neonates is thus similar to that of adults. However, due to the intrinsic hyporesponsiveness of neonatal platelets and NO-synergistic phar macodynamic profiles of other drugs (e.g., prostacyclin), possible adverse effects of iNO must be considered.