BACKGROUND: In patients receiving extracorporeal membrane oxygenation (ECMO), standard practice is full-dose intravenous unfractionated heparin (UFH) targeting an activated partial thromboplastin time of 2·0-2·5 times baseline to reduce thrombotic risk. This approach can increase bleeding without further reducing thrombosis compared with low-dose UFH. Robust evidence to guide anticoagulation targets is absent because anticoagulation targets in ECMO have never been assessed in a sufficiently powered randomised trial. We aimed to determine whether low-dose UFH or therapeutic low-molecular-weight heparin (LMWH) is non-inferior to standard-dose UFH in patients receiving ECMO.
METHODS: In this open-label, three-arm, randomised, non-inferiority trial at seven Dutch intensive care units (ICUs), adults aged 18 years or older supported with veno-venous or veno-arterial ECMO at the ICU without vital indication for full-dose anticoagulation (eg, mechanical mitral valve) were randomly assigned to intravenous standard-dose UFH (activated partial thromboplastin time 2·0-2·5 times baseline), intravenous low-dose UFH (1·5-2·0 times baseline), or therapeutic subcutaneous LMWH. The primary outcome was a composite of severe bleeding during ECMO support, severe thromboembolic complications during ECMO support, or all-cause mortality at 6 months, and was assessed in all randomly assigned patients with deferred informed consent and 6-month follow-up data according to the intention-to-treat principle. Non-inferiority was met if the upper 95% CI limit for the absolute risk difference was less than 7·5 percentage points. This trial is registered at ClinicalTrials.gov (NCT04536272) and the Dutch trial register (NL7976).
FINDINGS: Between Oct 22, 2020, and Sept 12, 2024, 330 patients were enrolled: 110 were randomly assigned to standard-dose UFH, 110 to low-dose UFH, and 110 to LMWH. Of 330 enrolled patients, 320 (225 [70%] males, 95 [30%] females; median age 56 years [IQR 45-65]; 255 [80%] White ethnicity) were analysed at 6 months. The composite primary outcome occurred in 87 (81%) of 107 patients with standard-dose UFH, 78 (72%) of 108 with low-dose UFH (absolute risk difference -9·1 percentage points [95% CI -20·3 to 2·1]), and 79 (75%) of 105 with LMWH (-6·1 percentage points [-17·2 to 5·0]), meeting non-inferiority for both interventions. The frequency of severe bleeding was lower with low-dose UFH and LMWH than with standard-dose UFH (63 [58%] patients and 62 [59%] vs 70 [65%]), without excess severe thromboembolic complications (11 [10%] and nine [9%] vs 12 [11%]), although these differences did not reach statistical significance. At 6 months, 54 (50%) patients in the standard-dose UFH group, 45 (42%) in the low-dose UFH group, and 46 (44%) in the LMWH group had died.
INTERPRETATION: Low-dose UFH and therapeutic LMWH were non-inferior to standard-dose UFH. This finding supports reconsideration of anticoagulation targets in ECMO. Given the global expansion of ECMO, these findings suggest that reduced anticoagulation targets could substantially reduce bleeding-related harm.
FUNDING: ZonMw.
| Discipline Area | Score |
|---|---|
| Physician |  |
, McMaster University