Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

Abstract

Objective: Ibuprofen might have advantages over indomethacin, when used to effectuate closure of a neonate's patent ductus arteriosus (PDA). Several previous studies indicate that platelet plug formation is impaired after administration of indomethacin, but it is not clear whether a similar impairment occurs following ibuprofen dosing.Study Design: We performed template bleeding times and PFA-100 tests (platelet function analyzer) on 20 neonates who had a PDA, before and again at various preset intervals following ibuprofen dosing.Result: Patients ranged from 23 to 40 weeks gestation and weighed 511 to 2566 g. Their first dose of ibuprofen was administered at 72 h (18 to 363 h) after birth (median, range). None of the subjects had clinical bleeding problems noted during the days they received ibuprofen dosing. The template bleeding times before dosing ranged from 135 to 450 s. Repeat tests were performed in groups of four, at 2 h, 4 to 6 h, 12 to 18 h, 24 h after the first dose, and at 2 h after the third dose of ibuprofen. No changes in bleeding times were detected. (P ¼ 0.299) A PFA-100 time was performed on all 20 patients before and again after the ibuprofen administration. However, 3 of the 40 tests were unsuccessful, because of microclots in the blood sample (n ¼ 1) or failure of the analyzer for an unspecified reason (n ¼ 2). Before the dosing the PFA-100 time ranged from 52 to 300 s. A paired t-test showed a slight but statistically significant lengthening in PFA-100 time after the ibuprofen administration (P ¼ 0.019). The correlation between the bleeding time and the PFA-100 was poor (R 2 ¼ 0.212, P ¼ 0.576). Conclusion:On the basis of our present studies, we speculate that ibuprofen lysine administration to neonates with a PDA, when used according to the manufacturer's recommendations, has little adverse effect on platelet plug formation. This information might be a factor to consider when deciding whether to select indomethacin or ibuprofen for PDA closure.

Effect of ampicillin on the bleeding time of neonatal intensive care unit patients

“…The bleeding times we measured in this study were shorter than those we reported in a recent study of ibuprofen lysine. 1 In fact, the longer bleeding times we observed after three or four doses of ampicillin were similar to the pre-ibuprofen bleeding times we reported earlier. This apparent discrepancy might be because all neonates in our ibuprofen study had already received several doses of ampicillin, and thus they already had some degree of platelet impairment before the ibuprofen doses were begun.…”

“…A template bleeding time was performed (by MJS or RDC) using methods described earlier. 1,[10][11][12] The before and after ampicillin bleeding time pairs were always performed by the same technician. Briefly, a bloodpressure cuff appropriate for the infant's size was placed on an upper extremity and set at a pressure equal to the last measured mean blood pressure.…”

“…As two PFA-100 tests were performed on each patient (one before and one after ampicillin) eliminating the adenosine diphosphate cartridge resulted in 1.8 ml less blood than would otherwise be needed. 1 Groups of patients were to receive the studies 2 to 6 h after the first dose of ampicillin, 8 to 12 h after the third dose or 8 to 12 h after the fourth dose of ampicillin. Descriptive statistics were calculated using Statit (Corvallis, OR, USA).…”

“…[1][2][3] Ampicillin is one of the antibiotics best known to damage platelet function 4-9 but we are unaware of any studies of this effect of ampicillin in neonates.…”

Learning to live with patency of the ductus arteriosus in preterm infants

“…67 However, ibuprofen does not appear to prolong bleeding times in preterm infants, leading to speculation that it may be preferable to indomethacin for this indication. 68 Although these observations are not definitive, they raise concern that treatment with indomethacin (and possibly with other COX inhibitors) could ultimately increase the number of infants who require ductal ligation, despite inducing early ductal constriction.…”