Abstract

Extracorporeal membrane oxygenation (ECMO) is a valuable modality used to support neonates, children, and adults with cardiorespiratory failure refractory to conventional therapy. It requires use of anticoagulation to prevent clotting in the extracorporeal circuit. Balancing bleeding from excessive anticoagulation with thrombotic risk remains a difficult aspect of ECMO care. Despite many advances in ECMO technology, better understanding of the coagulation cascade and new monitoring schemes to adjust anticoagulation, bleeding and thrombosis remain the most frequent complications in ECMO and are associated with morbidity and mortality. In neonates, ECMO is also complicated by the immature hemostatic system, laboratory testing norms which are not specific for neonates, lack of uniformity in management, and paucity of high-quality evidence to determine best practices. Traditional anticoagulation focuses on the use of unfractionated heparin. Direct thrombin inhibitors are also used but have not been well-studied in the neonatal ECMO population. Anticoagulation monitoring is complex and currently available assays do not take into account thrombin generation or platelet contribution to clot formation. Global assays may add valuable information to guide therapy. This review provides an overview of hemostatic alterations, anticoagulation, monitoring and management, novel anticoagulant use, and circuit modifications for neonatal ECMO. Future considerations are also presented.

Highlights

  • Extracorporeal membrane oxygenation (ECMO) is a valuable modality used to support neonates, children, and adults with cardiorespiratory failure refractory to conventional therapy

  • The developmental hemostatic system, increased risk for hemorrhage in the developing brain, heterogeneous disease processes that lead to initiation of ECMO, variability in anticoagulation strategies and lack of high-quality evidence to direct practice all contribute to the challenges in managing anticoagulation in the neonatal population

  • We provide an overview of developmental hemostasis, hemostatic alterations, anticoagulation, monitoring, management, and novel anticoagulant use as well as circuit modifications for neonatal ECMO

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Summary

INTRODUCTION

Extracorporeal membrane oxygenation (ECMO) is a valuable modality used to support neonates, children, and adults with cardiorespiratory failure refractory to conventional therapy. In the BATE study, 60– 77% of neonates placed on ECMO for respiratory or cardiac indications suffered from bleeding events and 19–23% of these consisted of intracranial hemorrhage. In the BATE study, 4– 13% of these thrombotic events were patient-related (intracranial infarction, limb ischemia, aortopulmonary shunt clot, and other) and 25–40% were circuit-related. Both bleeding and thrombosis increased morbidity and mortality [3]. The developmental hemostatic system, increased risk for hemorrhage in the developing brain, heterogeneous disease processes that lead to initiation of ECMO, variability in anticoagulation strategies and lack of high-quality evidence to direct practice all contribute to the challenges in managing anticoagulation in the neonatal population. We provide an overview of developmental hemostasis, hemostatic alterations, anticoagulation, monitoring, management, and novel anticoagulant use as well as circuit modifications for neonatal ECMO

DEVELOPMENTAL HEMOSTASIS
Thrombin Generation
Platelet Activation and Von Willebrand Factor
Additional Considerations
Unfractionated Heparin
Direct Thrombin Inhibitors
Antiplatelet Agents
Circuit Modifications
Mediates coronary vasodilation
ANTICOAGULATION MONITORING
TEG or ROTEM Guided Algorithm
Novel Global Assays
Transfusion Thresholds
Additional Circuit Modifications
Targeted Animal Studies
Phenotyping and Genomics
Findings
CONCLUSION
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