Anticoagulation with Intravenous Direct Thrombin Inhibitors in Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review of the Literature
Systematic review published in Semin Thromb Hemost (2023)
Abstract
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Systematic review of 28 studies (329 patients) of DTIs in pediatric ECMO. Bivalirudin used in 96.7% of patients, argatroban 2.7%, lepirudin 0.6%; thromboembolism, bleeding, death in 17%, 17%, 23% by drug.
Why This Matters for Hirudotherapy
This systematic review of 28 studies (14 case reports, 13 retrospective, 1 prospective; 329 patients under 18 years) characterized intravenous direct thrombin inhibitors used for anticoagulation in pediatric ECMO, finding bivalirudin in 96.7% of patients, argatroban in 2.7%, and lepirudin in 0.6%; bleeding and thromboembolic events were each reported in 17% of patients. For ASH, this review carries defensible relevance because lepirudin is recombinant hirudin derived from the medicinal leech (Hirudo medicinalis), placing a leech-secretome product within the spectrum of DTIs evaluated in this high-acuity population, and the reported lepirudin infusion dose (0.14 ± 0.02 mg/kg/h) with laboratory monitoring data adds translational context for clinicians interested in hirudin-based anticoagulation. An honest caveat is that the included evidence is predominantly observational, and the abstract explicitly states that prospective studies are warranted to establish dosing, monitoring, safety, and efficacy of these agents in pediatric ECMO.
Citation
Anticoagulation with Intravenous Direct Thrombin Inhibitors in Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review of the Literature.
Kiskaddon AL et al. · Seminars in thrombosis and hemostasis, 2023
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