Pharmacodynamic effects of clopidogrel in pediatric cardiac patients: a comparative study of platelet aggregation response.

Published

Journal Article

Little data on pediatric percent platelet aggregation (%PA) exist in the literature, particularly in cardiac patients and in response to clopidogrel. The objectives were to estimate the %PA range expected in pediatric patients and to measure the clopidogrel effect on %PA in the PICOLO (Platelet Inhibition in Children on Clopidogrel) trial. To estimate a neonatal/infant %PA response range, %PA induced by 5 µM adenosine diphosphate (ADP) was assessed using light transmission aggregometry in 16 cord and 11 normal adult blood samples and prior to clopidogrel therapy in 49 neonatal and 49 infant/toddler cardiac patients enrolled in PICOLO. The %PA induced by 5 µM thrombin receptor-activating peptide (TRAP) was also assessed for 10 neonates and 21 infants/toddlers enrolled in PICOLO and compared with 11 adult samples. Percent inhibition of platelet aggregation (%IPA) induced by 5 µM ADP at steady-state clopidogrel levels was assessed in 33 neonates and 39 infants/toddlers. ADP-induced %PA was lowest in cord blood samples, intermediate in study neonates and infants/toddlers, and highest in adults. Similarly, TRAP-induced platelet aggregation was lower in neonates and infants/toddlers than adults. For all groups, %PA and %IPA were highly variable, with 11% of neonates and 13% of infants/toddlers showing <10% IPA. In conclusion, ADP- and TRAP-induced %PA is lower in pediatric cardiac patients than normal adults, but highly variable in both. The lower baseline %PA may explain why the pediatric clopidogrel dose providing 30-50% IPA (0.20 mg/kg/day) is lower than a simple weight-based extrapolation of the adult dose (75 mg/day) providing similar inhibition.

Full Text

Duke Authors

Cited Authors

  • Jennings, LK; Michelson, AD; Jacoski, MV; Tyagi, A; Grgurevich, S; Li, JS; Picolo Investigators,

Published Date

  • 2012

Published In

Volume / Issue

  • 23 / 6

Start / End Page

  • 430 - 438

PubMed ID

  • 22309046

Pubmed Central ID

  • 22309046

Electronic International Standard Serial Number (EISSN)

  • 1369-1635

Digital Object Identifier (DOI)

  • 10.3109/09537104.2011.650244

Language

  • eng

Conference Location

  • England