P2.017: Rethinking Anticoagulation in Pediatric ECMO: Insights from Bivalirudin Use

Background: Choice of anticoagulation medication in Pediatric ECMO remains controversial. There is limited data on the subject that is often extrapolated from adult studies which creates challenges in interpretation due to children’s differing pharmacokinetics, causes of thromboembolism, and anticoagulation administration and monitoring.

Methods: This systematic review was conducted per PRISMA guidelines, searching Medline via PubMed, Cochrane Central, Scopus, and ClinicalTrials.gov.Key search terms were ECMO and anticoagulants, particularly bivalirudin compared with heparin in pediatric ECMO

Results: In this systematic review, eight studies were selected from an initial pool of 214, focusing on the use of anticoagulants in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO). Collectively, these studies encompassed a total of 446 participants and provided insights into the efficacy and feasibility of bivalirudin as an alternative to heparin, particularly for patients with contraindications to heparin.
Efficacy and Therapeutic Goals: Bivalirudin was consistently reported as an effective alternative to heparin. One study noted that patients reached their therapeutic activated partial thromboplastin time (aPTT) goal in a median of 6.1 hours, maintaining the therapeutic range for an average of 61.9% of the time. Another study highlighted a significantly shorter time to reach therapeutic anticoagulation levels with bivalirudin (11 hours) compared to heparin (29 hours, p = 0.01).
Dosage and Therapeutic Range: A study detailed the median bivalirudin dose as 0.37 mg/kg/h, with an interquartile range of 0.21-0.56 mg/kg/h, noting that ventricular assist device (VAD) patients required higher doses than ECMO patients. The bivalirudin group also had a higher percentage of aPTT values within the therapeutic range during the first week (65% vs. 44% for heparin).
Complications and Safety: While bivalirudin demonstrated fewer bleeding events and required fewer transfusions than heparin, some studies reported higher thrombotic complications, with a notable proportion of patients requiring circuit changes. However, a multi-centric study found that bivalirudin was associated with significantly lower odds of bleeding and thrombotic events, as well as transfusion requirements.
Cost and Resource Utilization: The comprehensive cost analysis showed that the daily cost of bivalirudin was significantly lower than that of heparin ($494 vs. $1,184; p = 0.03). Furthermore, the rate of circuit interventions was lower in patients on bivalirudin.
Clinical Outcomes: Bivalirudin was linked to a 50% reduction in hospital mortality and higher odds of intact neurological outcomes at discharge compared to unfractionated heparin (UFH). Additionally, significant correlations were observed between bivalirudin dose and coagulation parameters such as PTT, INR, and ACT.

Conclusion: Bivalirudin is a feasible alternative to heparin in pediatric ECMO especially in patients with contraindications to Heparin, offering faster therapeutic levels, reduced bleeding, and cost savings. Further research is needed to optimize dosing and validate long-term benefits.