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Pharmacokinetics and Pharmacodynamics of Anticoagulants in Paediatric Patients

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Abstract

Given the rising incidence of thrombotic complications in paediatric patients, understanding of the pharmacologic behaviour of anticoagulant drugs in children has gained importance. Significant developmental differences between children and adults in the haemostatic system and pharmacologic parameters for individual drugs highlight potentially unique aspects of anticoagulant pharmacology in this special and vulnerable population. This review focuses on pharmacologic information relevant to the dosing of unfractionated heparin, low molecular weight heparin, warfarin, bivalirudin, argatroban and fondaparinux in paediatric patients. The bulk of clinical experience with paediatric anticoagulation rests with the first three of these agents, each of which requires higher bodyweight-based dosing for the youngest patients, compared with adults, in order to achieve comparable pharmacodynamic effects, likely related to an inverse correlation between age and bodyweight-normalized clearance of these drugs. Whether extrapolation of therapeutic ranges targeted for adult patients prescribed these agents is valid for children, however, is unknown and a high priority for future research. Novel oral anticoagulants, such as dabigatran, rivaroxaban and apixaban, hold promise for future use in paediatrics but require further pharmacologic study in infants, children and adolescents.

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Acknowledgments

The authors thank Linda DeMuro, MLS, and Susi Miller, MLIS, AHIP, from the Grant Morrow III, MD Medical Library at Nationwide Children’s Hospital (Columbus, OH, USA) for their assistance in designing the search strategy and performing the initial literature search. Drs Yee and Young have no financial conflicts of interest to disclose. Dr O’Brien is a member of a Bristol-Myers Squibb advisory board for paediatric apixaban studies.

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Authors and Affiliations

  1. Texas Children’s Hospital, Baylor College of Medicine, 6701 Fannin Street, Suite 1580, Houston, TX, 77030, USA

    Donald L. Yee

  2. Center for Innovation in Pediatric Practice, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    Sarah H. O’Brien

  3. Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Guy Young

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  1. Donald L. Yee
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Correspondence to Donald L. Yee.

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Yee, D.L., O’Brien, S.H. & Young, G. Pharmacokinetics and Pharmacodynamics of Anticoagulants in Paediatric Patients. Clin Pharmacokinet 52, 967–980 (2013). https://doi.org/10.1007/s40262-013-0094-1

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  • DOI: https://doi.org/10.1007/s40262-013-0094-1

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