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Background  Hemorrhagic events remain a major concern in patients under extracorporeal membrane oxygenation (ECMO) support. We tested the association between anticoagulation levels and hemorrhagic events under ECMO using anti-Xa activity monitoring.    Methods  We performed a retrospective multicenter cohort study in three ECMO centers. All adult patients treated with veno-venous (VV)- or veno-arterial (VA)-ECMO in 6 intensive care units between September 2017 and August 2019 were included. Anti-Xa activities were collected until a hemorrhagic event in the bleeding group and for the duration of ECMO in the non-bleeding group. All dosages were averaged to obtain means of anti-Xa activity for each patient, and patients were compared according to the occurrence or not of bleeding.    Results  Among 367 patients assessed for eligibility, 121 were included. Thirty-five (29%) presented a hemorrhagic complication. In univariate analysis, anti-Xa activities were significantly higher in the bleeding group than in the non-bleeding group, both for the mean anti-Xa activity (0.38 [0.29–0.67] vs 0.33 [0.22–0.42] IU/mL;  p  = 0.01) and the maximal anti-Xa activity (0.83 [0.47–1.46] vs 0.66 [0.36–0.91] IU/mL;  p  = 0.05). In the Cox proportional hazard model, mean anti-Xa activity was associated with bleeding ( p  = 0.0001). By Kaplan–Meier analysis with the cutoff value at 0.46 IU/mL obtained by ROC curve analysis, the probability of survival under ECMO without bleeding was significantly lower when mean anti-Xa was > 0.46 IU/mL ( p  = 0.0006).    Conclusion  In critically ill patients under ECMO, mean anti-Xa activity was an independent risk factor for hemorrhagic complications. Anticoagulation targets could be revised downward in both VV- and VA-ECMO.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13054-021-03554-0.

Anti-Xa activity and hemorrhagic events under extracorporeal membrane oxygenation (ECMO): a multicenter cohort study