Liberal or restrictive transfusion for veno-arterial extracorporeal membrane oxygenation patients: a target trial emulation using the OBLEX study data

BACKGROUND: The optimal transfusion threshold for patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains uncertain. METHODS: We used data from OBLEX (ClinicalTrials.gov: NCT03714048), an international, prospective, observational study conducted across 12 centres in Australia, Europe, and North America between 2019 and 2022. The study collected information on patient demographics, bleeding risk factors, transfusion practices during the first seven days of ECMO, and in-hospital mortality. Using these data, we emulated a target trial comparing the effects of liberal transfusion practice (transfusion initiated at Hb ≥ 90 g/L) and restrictive transfusion practice (transfusion initiated at Hb ≤ 70 g/L) on hospital mortality within seven days of ECMO initiation. Sequential trials approach was used to estimate the causal contrast. RESULTS: A total of 534 patients were included, with 46% dying during hospitalisation. After accounting for potential confounders, the liberal transfusion practice demonstrated a modest survival benefit within the first two days of ECMO, with differences in survival probabilities of 12% (95% CI 3% to 21%) at day 2 and 13% (95% CI 2% to 25%) at day 3, corresponding to the number needed to treat (NNT) of 8 and 7 respectively. No differences in survival benefit were found after day 3. These results were consistent across sensitivity and exploratory analyses. CONCLUSION: This target trial emulation study suggests that a liberal transfusion threshold may provide a modest survival benefit during the early course of VA-ECMO, but no benefit afterwards. Prospective studies are needed to confirm these findings, assess clinical adoption, and investigate underlying mechanism.