Anticoagulation for ECMO: Indications, Challenges and Future Directions

by Alessandra Riccio, MD
Resident Member, SOCCA
Weill Cornell Medical Center, New York, NY

Ankur Srivastava, MD
Member, SOCCA
Weill Cornell Medical Center, New York, NY

Margo Hoyler, MD
Member, SOCCA Communications Cmte
Member, SOCCA CPC MCS Subcommittee
Weill Cornell Medical Center, New York, NY

Volume 36 | Issue 4 | Dec 2025

As ECMO use continues to rise, optimal anticoagulation management is an increasingly salient clinical concern.1 Although anticoagulation in ECMO is empirical, the balance between preventing thrombosis and avoiding life-threatening hemorrhage remains a clinical challenge, particularly given the hemostatic dysregulation inherent to ECMO.2,3 This article will review the rationale, pharmacologic strategies, and urgent clinical questions regarding anticoagulation for ECMO patients.

Anticoagulation: Rational and Indications
Thrombotic and hemorrhagic complications may occur in up to 37% and 47% of V-V ECMO patients, respectively, and 15% and 51% of V-A ECMO patients.4,5 Hypercoagulability may develop due to clotting-cascade activation at the blood-device interface, critical illness, non-pulsatile flow, hemolysis and transfusions, among many other factors.3,6 Conversely, bleeding may occur due to vascular complications, fibrinolysis, platelet dysfunction and acquired von Willebrand deficiency, in addition to excessive anticoagulation.3,6

Guidelines recommend therapeutic anticoagulation in ECMO patients in order to prevent circuit thrombosis and venous and arterial thromboembolism.7 However, a growing body of data suggests that certain ECMO patient populations may demonstrate superior outcomes in the absence of anticoagulation. Several retrospective studies report comparable thrombosis rates with fewer hemorrhagic complications and reduced transfusion requirements in patients managed without continuous anticoagulation.8,9 These conclusions, however, are limited by retrospective design with inconsistent reporting of outcomes. Current guidelines continue to support routine use of therapeutic anticoagulation.7,22

Choice of Anticoagulant: Heparin versus Direct Thrombin Inhibitors
Current guidelines recommend therapeutic anticoagulation with unfractionated heparin (UFH) for V-V and V-A ECMO patients.7,22 UFH is advantageous for its cost-effectiveness, reversibility, ease of monitoring and general familiarity. However, UFH dose-effects are often variable and unpredictable, and patients may develop heparin-resistance due to anti-thrombin III depletion. Heparin also carries a risk of heparin-induced thrombocytopenia (HIT), which may itself be challenging to diagnose given the multifactorial nature of thrombocytopenia and hypercoagulability in ECMO patients, as previously described.10 In cases of HIT and anti-thrombin III deficiency, direct thrombin inhibitors (DTIs), such as bivalirudin and argatroban, may be used. Even in non-HIT patients, some centers routinely use DTIs due to their predictable dose effect.11 Disadvantages of DTIs include a lack of antidote and need for dose-adjustment in patients with renal and/or hepatic dysfunction (for bivalirudin and argatroban, respectively). A recent meta-analysis by Hasegawa et al. found significantly lower short-term mortality in EMCO patients receiving bivalirudin compared to heparin, though conclusions remain limited by observational data.11 Additional retrospective studies report comparable, if not reduced, rates of hemorrhagic and thrombotic complications in patients receiving bivalirudin compared to heparin.12-14 Kaseer et al revealed the percentage of time activated partial thromboplastin time (aPTT) was within the therapeutic range was higher with bivalirudin than UFH (50% vs 85.7%; P = .007) providing a possible mechanism to the reduced rates of hematologic complications.15 While these findings suggest that DTIs may offer a safe and effective alternative to UFH, prospective controlled trials are needed to confirm these trends.

Anticoagulation Monitoring
Optimal monitoring strategies and therapeutic targets for ECMO anticoagulation remain debated. An international survey of ECMO centers found that the three most commonly-used methods were activated partial thromboplastin time (aPTT) (41.8%), activated clotting time (ACT) (30%), and anti-factor-Xa (anti-Xa) activity (22.7%).16 Current ELSO practice guidelines recommend targeting anti-Xa level of 0.3-0.5 U/mL, or alternatively a aPTT of 50–70 seconds, for UFH therapy. 7 However, aPTT is influenced by coagulation factor levels (II, VIII, antithrombin), circulating inhibitors, and assay variability, complicating standardization.17

Furthermore, discordance between aPTT and anti-Xa levels has been noted to occur in one third of cases, suggesting opportunity for under- and over-anticoagulation.17 This discordance may be particularly likely in the setting of liver dysfunction and hyperbilirubinemia; in this scenario, Xa is often unreliable.18,22 In all cases, clinicians must interpret results within the context of the patient’s physiology and coagulation profile. Additional point-of-care testing such as ACT and viscoelastic testing (e.g. ROTEM, TEG) have also been explored for anticoagulation monitoring. At heparin doses typically used in the ICU, ACT has shown limited sensitivity and poor correlation with UFH dose, aPTT, and anti-Xa levels.16,19 Viscoelastic testing, while useful for rapid assessment of global coagulation dynamics, has shown only nonsignificant trends toward reduced bleeding, thrombosis, and in-hospital mortality.20 These findings suggest that ACT and viscoelastic testing may serve best as adjunctive, rather than primary, monitoring tools.

Future Directions in Anticoagulation for ECMO
Overall, the current evidence underscores significant variability in anticoagulation strategies, monitoring methods, and clinical outcomes among patients receiving ECMO support. While emerging data suggest potential benefits of alternative anticoagulants such as bivalirudin and adjunctive monitoring modalities, the absence of robust prospective trials limits definitive conclusions. Standardized, evidence-based protocols are urgently needed to optimize anticoagulation management, balance bleeding and thrombotic risks, and ultimately improve patient outcomes

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