Abstract 1107 Poster Session IV, Tuesday, 5/4 (poster 228)

Indomethacin, a cyclooxygenase inhibitor, is currently being used to close patent ductus arteriosus' in premature neonates, but its effect on platelet aggregatory function has never been systematically studied. Inhaled nitric oxide (INO), a pulmonary vasodilator, has been recently introduced to treat infants with severe hypoxemic respiratory failure. As both agents are known to inhibit platelet aggregation, we here compared the magnitude and time-course of these effects in neonates.

Methods: From October 1997 to September 1998, we prospectively examined the collagen-induced platelet aggregatory function (Whole blood platelet-ionized calcium Lumi-aggrometer, Chrono-Log) in premature infants treated with indomethacin and compared that with critically ill infants treated with INO and mechanically ventilated neonates. Nineteen premature infants (birth weight 1020 ± 290 g, gestation 26 ± 3 weeks) treated with indomethacin were enrolled into the study. Eight critically ill infants (birth weight 2550 ± 1210 g, gestation 36 ± 6 weeks) treated with INO, and 10 mechanically ventilated neonates (birth weight 2430 ± 1220 g, gestation 35 ± 5 weeks) were recruited for comparison.

Results: Collagen (5 µg/mL) caused platelet aggregation of 24 ± 11 ohms in 19 premature infants before starting indomethacin (pretreatment baseline), which was not different from pretreatment baseline of 8 INO-treated infants (24 ± 9 ohms), and the aggregation response of 10 mechanically ventilated neonates (24 ± 8 ohms)(ANOVA). Indomethacin, given in 3 intravenous doses (0.2 mg/kg followed by 0.1 mg/kg at 12 and 36 hours later), significantly inhibited the ex-vivo platelet aggregatory response (26% of pretreatment baseline) (versus its pretreatment baseline and mechanically ventilated neonates, ANOVA). Indomethacin therapy caused persistent inhibition of platelet function for at least 24 hours after the third intravenous dose (54% of pretreatment baseline), and full normalization of platelet function occurred 3 to 7 days later. In contrast, critically ill infants treated with INO showed inhibited platelet function during INO (67% of pretreatment baseline) and normalized platelet function by 24 hours after discontinuation of INO.

Conclusion: We conclude that both agents cause reversible inhibition of platelet function, however, the effect of indomethacin is longer lasting than that of INO.