Response of neonatal platelets to nitric oxide in vitro.

OBJECTIVES

Several studies have demonstrated altered platelet function during nitric oxide inhalation (iNO) in adults and neonates. In vitro NO inhibits activation of fibrinogen receptor glycoprotein (GP) IIb/IIIa in a dose-dependent manner. In neonates GPIIb/IIIa response to stimulation is physiologically attenuated during the first days after birth in comparison to adults; the effects of NO on GPIIb/IIIa in neonates, however, are less established. 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 was stimulated in vitro with 10 microM ADP or 0.05 U/ml thrombin in the presence or absence of 10 microM SIN-1. GPIIb/IIIa activation was determined by two-color flow cytometry.

SETTING

Delivery department of an university hospital.

PATIENTS AND PARTICIPANTS

Ten healthy term neonates, their mothers and nonpregnant 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 the relative response to SIN-1 was similar in all three groups (70 +/- 5 %).

CONCLUSIONS

The relative amount of NO-induced inhibition of GPIIb/ IIIa activation in neonates is thus similar to that of adults. However, due to the intrinsic hyporesponsiveness of neonatal platelets and NO-synergistic pharmacodynamic profiles of other drugs (e.g., prostacyclin), possible adverse effects of iNO must be considered.