ECMO and Coagulation Test Correlation

Extracorporeal membrane oxygenation (ECMO) for respiratory failure, cardiogenic shock, and refractory cardiac arrest has become increasingly common since 2009.¹ ECMO therapy presents the unique challenge of balancing the risk of both bleeding and thrombotic complications. The Extracorporeal Life Support Organization (ELSO) recommends anticoagulation for most patients on ECMO but does not offer a preferred anticoagulant or monitoring strategy.²

Critically ill patients requiring ECMO are complex and predisposed to mechanical hemolysis, which increases plasma-free hemoglobin and bilirubin levels, which in turn may interfere with anticoagulation monitoring. Also, because coagulation tests are performed in vitro, they cannot account for the endothelial-cannula interaction on the coagulation cascade and response to anticoagulation in vivo during ECMO.

The correlation among activated partial thromboplastin time (aPTT), anti-Xa activity, and R-time measured with thromboelastography in response to treatment with unfractionated heparin is poorly described. It is unknown how values above and below the target range for these coagulation parameters are associated with mortality, bleeding events, and thrombotic complications.

Reisinger et al conducted a retrospective review of adults treated with ECMO in either the medical or cardiac ICU of a single center over a 5-year period.³ Patients were excluded if they were treated with ECMO for less than 6 hours, received anticoagulation with only argatroban or low-molecular-weight heparin, or did not have multiple simultaneous coagulation tests.

Among the study population, 41 patients were treated with venovenous ECMO (VV ECMO), 42 with venoarterial ECMO (VA ECMO), and 2 with venoarterial-venous ECMO (VAV ECMO). Of the 85 total ECMO patients who had clustered anticoagulation tests, the investigators analyzed 671 clusters with a median of 6 clusters per patient. They found poor correlation among all three coagulation tests, but the presence of discordant values was not associated with ICU mortality.

There were 57 bleeding events in this cohort, with most events being classified as minor bleeding and only seven major bleeding events. Prior to a bleeding event, proportions above the target range were not associated with bleeding for anti-Xa, aPTT, or R-time. When stratified to patients on VA ECMO, elevated anti-Xa level was associated with bleeding events, while aPTT and R-time were not. For those on VV ECMO, aPTT was associated with bleeding events while anti-Xa and R-time were not. Based on the discordance among values for anticoagulation monitoring strategies and the complex metabolic milieu of patients treated with ECMO, choice of anticoagulation monitoring should be individualized and multiple tests should be used to better characterize anticoagulation status.³

This study had many limitations, largely related to its retrospective nature. A major limitation was that treating physicians were not required to target any specific ranges for anticoagulation. Thus, the chosen target range represents a generally accepted target range for ECMO patients at this institution that may not be representative of the goals of the treating physicians. Since eligible patients were those who had clustered anticoagulation tests, this study is predisposed to bias with a patient population whose anticoagulation status was difficult to determine by treating clinicians. The results may not be applicable to all patients who are treated with ECMO.

Despite its limitations, this study highlights the risks associated with ECMO. Anticoagulation in this patient population is complex and may require monitoring of multiple coagulation tests versus monitoring a single test. Further research is needed to compare bleeding and thrombotic risk between different aPTT, anti-Xa, and R-time ranges for patients being treated with unfractionated heparin and direct thrombin inhibitors.

References

1. Tonna JE, Boonstra PS, MacLaren G, et al; Extracorporeal Life Support Organization (ELSO) Member Centers Group. Extracorporeal Life Support Organization Registry International Report 2022: 100,000 survivors. ASAIO J. 2024 Feb 1;70(2):131-143.
2. McMichael ABV, Ryerson LM, Ratano D, Fan E, Faraoni D, Annich GM. 2021 ELSO adult and pediatric anticoagulation guidelines. ASAIO J. 2022 Mar 1;68(3):303-310.
3. Reisinger AC, Schneider N, Koellinger M, et al. Anticoagulation monitoring strategies during extracorporeal membrane oxygenation (ECMO) therapy: differences between simultaneously obtained coagulation tests: a retrospective single-center cohort study. J Intensive Care Med. 2025 Feb 6:8850666241313357. Online ahead of print.