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

Abstract

Objective: Studies in adults indicate that ampicillin, in a dose-dependent manner, impairs platelet function and moderately prolongs the bleeding time (generally by 60 to 90 s). Unlike aspirin, the inhibition induced by ampicillin involves both reversible and irreversible mechanisms and is not observed immediately after initial dosing (generally requiring approximately 24 h). Ampicillin is administered commonly to neonatal intensive care unit (NICU) patients, but its effect on bleeding time in this population has not been reported earlier.Study Design: We performed neonatal template bleeding times and platelet function analyzer (PFA)-100 tests on 15 NICU patients before and at various intervals after intravenous ampicillin dosing.Result: Neonates were only studied if no beta-lactam antibiotics were administered to their mother during labor, and if they had ampicillin ordered by the clinician at a dose of 50 to 100 mg kg -1 every 12 h. Subjects ranged from 33 to 41 weeks gestation and weighed 1760 to 3835 g. Bleeding times before the first ampicillin dose (n ¼ 15) averaged 134 s (95% confidence interval (CI), 120 to 148 s) and PFA-100 times averaged 123 s (95% CI, 96 to 149 s). After the first dose of ampicillin (n ¼ 5), bleeding times and PFA-100 times did not increase, but after the third (n ¼ 5) and fourth doses (n ¼ 4) bleeding times lengthened by an average of 60 s (95% CI, 37 to 83 s, P<0.001) and PFA-100 times lengthened by an average of 20 s (95% CI, À20 to 60 s, P ¼ 0.15).Conclusion: Ampicillin administered intravenously to NICU patients prolongs the bleeding time, with a magnitude-of-effect and time-to-effect similar to that shown earlier in adults.

Effect of ampicillin on bleeding time in very low birth-weight neonates during the first week after birth

“…As we previously reported, we slightly modified the PFA-100 method in order to reduce the amount of blood needed. 5,9 Specifically, only the epinephrine cartridge (not the adenosine diphosphate cartridge) was used. To maintain the recommended ratio of blood to citrate (9:1), 90 ml of citrate was removed from each blood collection tube (BD Diagnostics, Franklin Lakes, NJ, USA) using a micropipetter (Finnpipettte, Thermo Fisher Scientific, Waltham, MA, USA).…”

“…A template bleeding time was performed (by MJS or RDC) using methods previously described. 3,5,9 The Intermountain Healthcare Clinical Hematology Laboratory performed the PFA-100 using the manufacture's recommendations (Dade Schering, Miami, FL, USA). Samples for PFA were drawn from a central line (UAC or UVC) when available, otherwise by venipuncture.…”

“…1,2 In contrast, very low birth-weight (VLBW, <1500 g) neonates often have subnormal platelet function, and bleeding times that are prolonged, inversely proportionate to their gestational age. [3][4][5] However, over the first 7 to 10 days following birth, the bleeding times of VLBW neonates generally improve (shorten) to about that of term neonates. 3,4 It is not clear whether ampicillin, which can impair platelet function in adults [6][7][8] and in term and late preterm neonates, 5 further lengthens the already prolonged bleeding times of VLBW neonates.…”

“…We measured platelet function in two ways, template bleeding time [1][2][3][4][5] and PFA-100 time. [9][10][11][12][13] As was the case in our previous study of ampicillin dosing to late preterm and term neonates, 5 we hypothesized that a few doses of ampicillin would have little effect on platelet function, but that ampicillin treatment for the entire first week would prolong the bleeding time.…”

Characterization of the Population Pharmacokinetics of Ampicillin in Neonates Using an Opportunistic Study Design

“…The PK of ampicillin have been studied in children and adults (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), but data on dosing in the neonatal population are sparse. Current dosing regimens take into account the gestational age (GA)-and postmenstrual age (PMA)-related variation in renal drug clearance and recommend lower doses and less frequent dosing in the most premature neonates (1).…”