Semin Thromb Hemost 2023; 49(07): 756-763
DOI: 10.1055/s-0043-1772838
Review Article

Anticoagulation with Intravenous Direct Thrombin Inhibitors in Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review of the Literature

Amy L. Kiskaddon
1   Department of Pharmacy, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
2   Department of Pediatrics, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Nhue L. Do
3   Division of Pediatric Cardiac Surgery, Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee
4   Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee
Pamela Williams
5   Medical Library, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
Marisol Betensky
6   Department of Pediatrics, Division of Hematology, Johns Hopkins School of Medicine, Baltimore, Maryland
7   Johns Hopkins All Children's Institute for Clinical and Translational Research, St. Petersburg, Florida
Neil A. Goldenberg
6   Department of Pediatrics, Division of Hematology, Johns Hopkins School of Medicine, Baltimore, Maryland
7   Johns Hopkins All Children's Institute for Clinical and Translational Research, St. Petersburg, Florida
8   Departments of Pediatrics and Medicine, Division of Hematology, Johns Hopkins School of Medicine, Baltimore, Maryland
› Author Affiliations


Although intravenous (IV) direct thrombin inhibitors (DTI) have gained interest in pediatric extracorporeal membrane oxygenation (ECMO), dosing and safety information is limited. The objective of this systematic review was to characterize DTI types, dosing, monitoring, and outcomes (bleeding and thromboembolic) in pediatric ECMO patients managed with IV DTIs. We conducted searches of MEDLINE (Ovid) and Embase (Elsevier) from inception through December 2022. Case reports, retrospective studies, and prospective studies providing per-patients or summary data for patient(s) <18 years of age receiving IV DTI for ECMO anticoagulation were included. Study selection and data extraction were conducted independently by two reviewers. A total of 28 studies: 14 case reports, 13 retrospective studies, and 1 prospective study were included, totaling 329 patients. Bivalirudin was utilized in 318 (96.7%), argatroban in 9 (2.7%), and lepirudin in 2 (0.6%) patients. Infusion dosing included: bivalirudin 0.14 ± 0.37 mg/kg/h, argatroban 0.69 ± 0.73 µg/kg/min, lepirudin 0.14 ± 0.02 mg/kg/h. Laboratory monitoring tests utilized were the activated clotting time, activated partial thromboplastin time (aPTT), diluted thrombin time, and thromboelastography measures. The aPTT was utilized in most patients (95%). Thromboembolism, bleeding, or death were observed in 17%, 17%, and 23% of bivalirudin, argatroban, and lepirudin patients, respectively. Bivalirudin appears to be the most frequently used DTI in pediatric ECMO. Dosing and laboratory monitoring varied, and bleeding and thromboembolic events were reported in 17% of patients. Prospective studies are warranted to establish dosing, monitoring, safety, and efficacy of bivalirudin and other IV DTI in pediatric ECMO.

Supplementary Material

Publication History

Article published online:
29 August 2023

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