A narrative review of antithrombin use during veno-venous extracorporeal membrane oxygenation in adults: rationale, current use, effects on anticoagulation, and outcomes

Abstract

Background: During extracorporeal membrane oxygenation, the large contact surface between the blood and the extracorporeal circuit causes a continuous activation of coagulation and inflammation. Unfractionated heparin, a glycosaminoglycan that must bind to antithrombin as a cofactor, is currently the standard anticoagulant adopted during extracorporeal membrane oxygenation. Antithrombin, beyond being a potent natural anticoagulant, acts in the cross-talk between coagulation and inflammatory system through anticoagulation and coagulation-independent effects. Objectives: In this review, we describe, in the adult setting of veno-venous extracorporeal membrane oxygenation, the pathophysiological rationale for antithrombin use, the current practice of administration, and the effects of antithrombin on anticoagulation, bleeding, and outcomes. Data sources: Studies on adults (18 years or older) on veno-venous extracorporeal membrane oxygenation published from 1995 to 2018 in order to evaluate the use of antithrombin. Results: In adults on veno-venous extracorporeal membrane oxygenation, antithrombin supplementation has a highly pathophysiological rationale since coagulation factor consumption, systemic inflammatory response syndrome, and endothelial activation are triggered by extracorporeal membrane oxygenation. Eleven articles are focused on the topic but among the authors there is no consensus on the threshold for supplementation (ranging from 70% to 80%) as well as on the dose (rarely standardized) and time of administration (bolus vs continuous infusion). Consistently, antithrombin is considered able to achieve better anticoagulation targets in or not in the presence of heparin resistance. The impact of antithrombin administration on bleeding still shows contrasting results. Conclusion: Antithrombin use in veno-venous extracorporeal membrane oxygenation should be investigated on the threshold for supplementation, dose, and time of administration.

Circulating miRNAs as Promising Biomarkers to Evaluate ECMO Treatment Responses in ARDS Patients

“…The analysis also revealed that crucial proteins regulating the aforementioned pathways are targeted by eight deregulated miRNAs ( Figure 4 bottom). During ECMO, due to both ARDS pathogenesis [ 17 , 41 ] and the continuous contact surface between the blood and the ECMO circuit [ 18 ], different coagulative pathways were also regulated by F2, FN1, MPL, and TBXA2R protein (which are known as positive regulators of these pathways) [ 18 , 42 , 43 , 44 ] and tissue factor pathway inhibitor (TFPI) (a negative regulator of coagulation processes) [ 45 ]. We found that let-7f, miR-25, miR-200b and miR-566 were up-regulated after 14 days of ECMO treatment in group B patients, and those miRNAs target the aforementioned positive regulators.…”

“…Moreover, during ECMO, several coagulative and inflammatory cascades similar to systemic inflammatory response syndrome (SIRS) are activated when the patient’s blood is exposed to the surface of the ECMO circuit [ 17 ]. Different miRNAs are able to regulate both platelet activation and crucial proteins involved in the regulation of hemostatic processes [ 18 , 19 ]. miRNA biomolecules also seem to play an important role in the regulation of gene expression during the pathogenesis of ARDS, being deregulated in pulmonary and extrapulmonary ARDS patients [ 20 ], as well as in patients with different severity status of ARDS [ 21 ].…”

Thromboembolic disease in COVID-19 patients: A brief narrative review

“…Acquired von Willebrand disease, thrombocytopenia, and bleeding are known complications in patients on ECMO [97][98][99][100]. Studies have described the use of VV ECMO without anticoagulation to reduce bleeding risks, however, the artificial contact surface of ECMO circuit itself causes continuous activation of coagulation, creating a prothrombotic environment [101,102]. The thrombotic risk is further accentuated in the presence of uninhibited COVID-19 diseases.…”

Thromboembolische Erkrankung bei COVID-19-Patienten: Eine kurze narrative Übersichtsarbeit

“…In einigen Studien wurde über die Anwendung einer veno-venösen ECMO ohne Antikoagulation zur Verringerung des Blutungsrisikos berichtet. Allerdings führt die künstliche Kontaktoberfläche des ECMO-Kreislaufs selbst zu einer anhaltenden kontinuierlichen Aktivierung der Koagulation, wodurch ein prothrombotisches Milieu entsteht [101, 102]. Das Thromboserisiko wird durch das Vorliegen einer ungehemmten COVID-19-Erkrankung weiter verstärkt.…”