PB0626 - Intravenous direct thrombin inhibitors for acute thromboembolism or heparin-induced thrombocytopenia with thrombus in children: A systematic review

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Amy Kiskaddon, PharmD, MBA

Assistant Professor of Pediatrics
Johns Hopkins University, Florida, United States

Co-Author(s)

JB

Joshua Branstetter

Clinical Pharmacy Specialist
Children's Hospital of Atlanta
Atlanta, Georgia, United States
PW

Pamela Williams

Medical Librarian
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Vera Ignjatovic, PhD, MBA

Professor of Pediatrics
Johns Hopkins All Children's Institute for Clinical and Translational Research; Department of Pediatrics, School of Medicine, Johns Hopkins University, United States
St Petersburg, Florida, United States
KW

Kristopher Wilhoit

Student
University of South Florida
Tampa, Florida, United States
Neil Goldenberg, MD,PhD

Departments of Pediatrics and Medicine
Johns Hopkins University School of Medicine, Baltimore, MD; Clinical and Data Coordinating Center for Pediatric Multicenter Studies, Johns Hopkins All Children’s Institute for Clinical and Translational Research, St. Petersburg, FL
Saint Petersburg, Florida, United States

Background: Intravenous (IV) direct thrombin inhibitors (DTI) are used for the prothrombotic state of heparin-induced thrombocytopenia with thrombus (HITT). There is increasing interest in their use for acute thromboembolism (TE). However, data are limited data regarding agent selection, dosing, and clinical outcomes in children.

Aims: To characterize IV DTI agents, dosing, and monitoring employed, bleeding, and mortality outcomes, in pediatric patients with TE or HITT.

Methods: MEDLINE, Embase, and Cochrane’s CENTRAL were searched from inception through July 2023. Case series, retrospective studies, and prospective studies providing per-patients or summary data for patients < 18 years of age with thromboembolism treated with an IV DTI were included. Selection and data extraction were conducted independently by two reviewers.

Results: A total of 17 studies ( 10 case series, 4 retrospective cohort, 3 prospective cohort studies), were included, totaling 87 patients. Indications included acute TE in 54 patients (62%) and HITT in 33 (38%). IV DTIs employed were bivalirudin, lepirudin, and argatroban in 58 (67%), 23 (26%), and 6 (7%) patients, respectively. Only 47 (54%) patients received a bolus dose, and average infusion doses for bivalirudin, lepirudin, and argatroban were 0.2 mg/kg/hr, 0.15 mg/kg/hr, and 1.2 mcg/kg/min, respectively. Laboratory monitoring included aPTT in 57/87 (65%) and ACT in 8/27 (30%). The resolution of TE was 53/69 (77%). Mortality was 8% (6/79). Bleeding was 17% (14/83). ISTH bleeding severity was not routinely reported among studies.

Conclusion(s): In this systematic review involving nearly 90 pediatric patients treated with IV DTI for acute TE or HITT, bivalirudin was most commonly employed, and the rate of resolution was high, despite a high acuity of the indication and high mortality in the population studied. Prospective collaborative studies are warranted to establish optimal dosing and more fully characterize TE and bleeding outcomes in pediatric patients receiving IV DTI for acute TE or HITT.