Challenges in Maintaining the Hemostatic Balance in Children Undergoing Extracorporeal Membrane Oxygenation: A Systematic Literature Review

Abstract

Background: Despite advances in technology and clinical experience, the incidence of hemostatic complications, including bleeding and thrombosis, remains high in children supported with extracorporeal membrane oxygenation (ECMO). These hemostatic complications are important to prevent, since they are associated with increased morbidity and mortality. This systematic literature review aims to outline the most important risk factors for hemostatic complications in children undergoing ECMO treatment, to summarize the reported alternative anticoagulant drugs used in pediatric ECMO and to describe studied associations between coagulation tests and hemostatic complications.Methods: A literature search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar in February 2020. Included studies were studies evaluating children (<18 years old) treated with ECMO, and studies evaluating risk factors for hemostatic complications, alternative anticoagulants, or the association between coagulation tests and hemostatic complications.Results: Out of 1,152 articles, 35 studies were included. Thirteen out of 49 risk factors were investigated in three or more studies. Most consistent results were found regarding ECMO duration and pH. However, evidence for risk factors was equivocal in the majority of studies, which is explained by the variability of populations studied, definitions of hemostatic complications, ECMO circuits, anticoagulation protocols, transfusion triggers and monitoring of anticoagulation. Five studies described alternative anticoagulants, including bivalirudin (n = 3), argatroban (n = 1) and FUT (n = 1). Higher anti-factor Xa levels were associated with less clotting events in one of nine studies, investigating the association between tests and hemostatic complications. Two studies revealed an association between anti-factor Xa assay-based protocols and a decreased number of transfusions, bleedings and need for circuit change.Conclusion: Studies regarding risk factors showed conflicting results and a few retrospective studies reported the use of new anticoagulants and data on coagulation tests in relation to hemostatic complications. To decrease hemostatic complications in ECMO children, prospective multicenter studies are needed with clear bleeding and thrombotic definitions, and the best possible standardization of ECMO circuits used, anticoagulation protocols, and transfusion triggers.

Is bivalirudin an alternative anticoagulant for extracorporeal membrane oxygenation (ECMO) patients? A systematic review and meta-analysis

“…However, the sample (58 patients) they included was too small, and most studies were case reports that could not compare the efficacy of bivalirudin and heparin. Drop JGF et al [8] conducted a systematic review to summarize the reported alternative anticoagulant drugs used in pediatric ECMO, and three studies described bivalirudin. Pharmacokinetic data, precise dosing, and monitoring guidelines are lacking.…”

Coagulation in pediatric extracorporeal membrane oxygenation: A systematic review of studies shows lack of standardized reporting

“…Many factors influence the risk for hemostatic complications, such as ECMO indications, ECMO circuitry, infections, surgery, underlying diseases, ECMO duration, and anticoagulation and transfusion management. 5 This review shows that the existing pediatric ECMO literature describing hemostatic tests and/or hemostatic outcomes does not clearly describe many essential factors that influence the hemostatic balance and, consequently, patient outcomes. To assess the contribution of individual components on outcome and to define best practice, it is important to be able to compare practices and results internationally.…”

“…Broman et al have made a first step toward a standardized approach to defining cannula practices in ECMO patients 15 . Pump type, mode, and location of cannulation have been associated with bleeding and thrombotic complications in several studies and are important to describe 5 . Given the increase in available technology for ECMO support, specific description of circuitry is essential to identify potential variances in technology performance and affect factors such as hemolysis and thrombosis.…”

“…14 15 Pump type, mode, and location of cannulation have been associated with bleeding and thrombotic complications in several studies and are important to describe. 5 Given the increase in available technology for ECMO support, specific description of circuitry is essential to identify potential variances in technology performance and affect factors such as hemolysis and thrombosis. Matching centers with similar circuitry and practice may limit variability and help provide scientifically valid results that can be extrapolated to the field.…”

“… 4 Research describing hemostatic tests and/or outcome in ECMO patients has primarily focused on the association between coagulation tests and hemostatic complications, identification of clinically relevant anticoagulation monitoring targets, the efficacy and safety of anticoagulant drugs, and the identification of clinically relevant thresholds for red blood cell and platelet transfusions. 5 In most studies, however, the population size is limited or comprises a specific group of patients. Moreover, there is a large variability in ECMO indications, coagulation protocols, ECMO circuitry, cannulation techniques, and transfusion thresholds.…”