Age-specific differences in the in vitro anticoagulant effect of Bivalirudin in healthy neonates and children compared to adults

Abstract

Bivalirudin is a reversible direct thrombin inhibitor that inhibits both bound and free thrombin and binds to the active (catalytic) and fibrinogen-binding sites of thrombin, with high affinity and specificity. Off-label use of bivalirudin in the paediatric population has increased, as an alternative to heparin, particularly in the setting of anticoagulation for patients undergoing coronary bypass surgery (CPB), extracorporeal life support (ECLS) and those on ventricular assist devices (VAD). This study aimed to determine the age-specific in vitro effect of bivalirudin in children compared to adults. Age-specific pools (neonates, ≤2 years, >2 to 5 years, 6 to 10 years, 11 to 17 years and Adults) were prepared using platelet poor plasma samples from 20 individuals per age group. Pooled plasma was spiked with increasing concentrations of Bivalirudin (from 0 g/mL to 10μg/mL), and thrombin inhibition was measured using standard coagulation assays. There was a significantly increased response to bivalirudin across all paediatric age groups as compared to adults. The age-specific difference in response to bivalirudin was specifically evident in neonates, where the potential to generate thrombin was decreased 2-fold compared to adults (p < 0.001). Our findings support the concept of age-specific pharmaco-dynamic responses to Bivalirudin and support the need for further ex vivo studies in hospitalised children to determine accurate clinical dosing recommendations.