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

Platelets. 2012;23(6):430-8. doi: 10.3109/09537104.2011.650244. Epub 2012 Feb 6.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adult
  • Arteries / drug effects
  • Arteries / pathology
  • Blood Platelets / drug effects
  • Child, Preschool
  • Clopidogrel
  • Double-Blind Method
  • Female
  • Fetal Blood / drug effects
  • Heart / drug effects
  • Heart Diseases / etiology
  • Heart Diseases / pathology
  • Heart Diseases / prevention & control*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Peptide Fragments / pharmacology
  • Placebos
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Thrombosis / complications
  • Thrombosis / drug therapy*
  • Thrombosis / pathology
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*


  • Peptide Fragments
  • Placebos
  • Platelet Aggregation Inhibitors
  • thrombin receptor peptide SFLLRNP
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine