Extracorporeal membrane oxygenation (ECMO) has become a cornerstone therapy in modern critical care medicine, providing life-sustaining cardiopulmonary support for patients with severe respiratory or cardiac failure. Despite its life-saving potential, ECMO therapy carries substantial risks, particularly bleeding and thrombotic complications. Anticoagulation management during ECMO remains one of the most debated areas in critical care, as clinicians must balance the risk of clot formation within the circuit against potentially catastrophic hemorrhage.
This 2026 systematic review and meta-analysis published in Frontiers in Medicine evaluated whether reduced-intensity or no heparin anticoagulation strategies are as safe and effective as standard-dose heparin protocols in adult ECMO patients. The study adhered to PRISMA guidelines and was registered in PROSPERO (CRD42025633878). A total of 11 studies involving 958 patients were included, comprising one randomized controlled trial and ten retrospective cohort studies.
Study Design and Population
The included studies evaluated adult patients receiving either veno-venous (VV) ECMO for respiratory failure or veno-arterial (VA) ECMO for cardiac support. Among the 958 patients analyzed, 167 received no anticoagulation, 404 received low-intensity anticoagulation, and 387 received standard-intensity heparin therapy.
Anticoagulation monitoring methods varied across institutions, including activated clotting time (ACT), activated partial thromboplastin time (aPTT), and anti-Xa assays. Importantly, comparisons were based on anticoagulation intensity rather than the monitoring modality used. Most cohort studies demonstrated moderate to high methodological quality using the Newcastle-Ottawa Scale.
Primary Outcome: Bleeding Complications
Bleeding is one of the most frequent and serious complications during ECMO support, with reported rates historically ranging from 27% to 60%. This meta-analysis demonstrated that reduced-intensity or no heparin anticoagulation significantly decreased bleeding events compared to standard anticoagulation.
The pooled analysis showed:
- Odds Ratio (OR) = 0.49
- 95% Confidence Interval (CI): 0.35–0.67
- P < 0.0001
- Low heterogeneity (I² = 43%)
Intracranial and gastrointestinal hemorrhages were notably reduced in the low/no heparin group. These findings align with growing clinical experience suggesting that modern ECMO circuits with improved biocompatibility may allow for lower systemic anticoagulation targets without compromising safety.
Secondary Outcome: Thrombotic Events
A critical concern with lowering anticoagulation intensity is the potential increase in thrombotic complications, including circuit thrombosis and systemic embolic events. However, this analysis found no statistically significant difference in thrombotic events between groups:
- OR = 1.00
- 95% CI: 0.65–1.54
- I² = 49%
The confidence interval suggests compatibility with either slight benefit or slight harm, but no clear increased risk was demonstrated. This finding supports the feasibility of lower anticoagulation targets, though subclinical microthrombi remain difficult to assess in available studies.
In-Hospital Mortality
Mortality is the ultimate clinical outcome of interest in ECMO research. The pooled mortality analysis demonstrated no significant difference between reduced-intensity and standard anticoagulation strategies:
- OR = 0.90
- 95% CI: 0.67–1.21
- I² = 41%
These findings suggest that lower anticoagulation intensity does not worsen survival outcomes. It is possible that reductions in bleeding risk offset any theoretical increase in thrombotic risk, leading to neutral overall mortality effects.
Red Blood Cell Transfusion Requirements
Four studies reported transfusion data. Although the analysis showed no statistically significant difference (OR = 0.29; 95% CI 0.08–1.02), substantial heterogeneity (I² = 76%) was observed. Sensitivity analysis revealed that variation in transfusion thresholds between centers contributed significantly to heterogeneity.
Transfusion practices in ECMO vary widely based on institutional protocols and patient severity, making definitive conclusions difficult. Nonetheless, a trend toward reduced transfusion in lower anticoagulation groups may suggest clinical benefit, though further research is needed.
Clinical Implications
The results of this meta-analysis support a growing paradigm shift toward individualized anticoagulation strategies in ECMO management. While traditional ELSO guidelines recommend ACT targets of 180–220 seconds and aPTT of 50–70 seconds, these recommendations are largely empiric. Emerging data suggest that carefully selected patients—particularly those at high bleeding risk—may safely tolerate lower anticoagulation intensity.
Technological advances in ECMO circuit biocompatibility and increasing use of anti-Xa monitoring may allow more precise anticoagulation titration. However, caution is warranted due to limitations in existing evidence.
Limitations
Several limitations must be acknowledged:
- Predominantly observational study designs
- Heterogeneous anticoagulation targets and monitoring methods
- Variable definitions of bleeding and thrombosis
- Limited randomized data (only one RCT included)
- Lack of patient-level adjustment for confounders
Given these factors, while reduced-intensity anticoagulation appears promising, definitive practice-changing conclusions require large-scale randomized controlled trials.
