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A systematic review of the evidence supporting post-operative antithrombotic use following cardiopulmonary bypass in children with CHD

Part of: Surgery

Published online by Cambridge University Press:  06 January 2022

Elizabeth J. Thompson
Affiliation:
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
Henry P. Foote
Affiliation:
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
Jennifer S. Li
Affiliation:
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
Alexandre T. Rotta
Affiliation:
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
Neil A. Goldenberg
Affiliation:
Department of Pediatrics and Medicine, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Institute for Clinical and Translational Research, Cancer and Blood Disorders Institute, and Heart Institute, Johns Hopkins All Children’s Hospital, St. Petersburg, FL, USA
Christoph P. Hornik*
Affiliation:
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
*
Author for correspondence: C. Hornik, MD, PhD, MPH, Department of Pediatrics, Duke University School of Medicine, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715 USA. Tel: 919-357-8145; Fax: 919-681-9457. E-mail: christoph.hornik@duke.edu

Abstract

Objectives:

To determine the optimal antithrombotic agent choice, timing of initiation, dosing and duration of therapy for paediatric patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods:

We used PubMed and EMBASE to systematically review the existing literature of clinical trials involving antithrombotics following cardiac surgery from 2000 to 2020 in children 0–18 years. Studies were assessed by two reviewers to ensure they met eligibility criteria.

Results:

We identified 10 studies in 1929 children across three medications classes: vitamin K antagonists, cyclooxygenase inhibitors and indirect thrombin inhibitors. Four studies were retrospective, five were prospective observational cohorts (one of which used historical controls) and one was a prospective, randomised, placebo-controlled, double-blind trial. All included were single-centre studies. Eight studies used surrogate biomarkers and two used clinical endpoints as the primary endpoint. There was substantive variability in response to antithrombotics in the immediate post-operative period. Studies of warfarin and aspirin showed that laboratory monitoring levels were frequently out of therapeutic range (variably defined), and findings were mixed on the association of these derangements with bleeding or thrombotic events. Heparin was found to be safe at low doses, but breakthrough thromboembolic events were common.

Conclusion:

There are few paediatric prospective randomised clinical trials evaluating antithrombotic therapeutics post-cardiac surgery; most studies have been observational and seldom employed clinical endpoints. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal drug, timing of initiation, dosing and duration to improve outcomes by limiting post-operative morbidity and mortality related to bleeding or thrombotic events.

Type
Review
Copyright
© The Author(s), 2022. Published by Cambridge University Press

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