Clinical Outcomes of Routine Antithrombin Supplementation During Extracorporeal Membrane Oxygenation

Introduction: Routine antithrombin monitoring and supplementation during extracorporeal membrane oxygenation (ECMO) is common. While backed by physiologically sound rationale, the clinical utility of this practice remains unclear. The objective of this systematic review was to evaluate the evidence for antithrombin supplementation during ECMO and its impact on clinical outcomes.


Methods: We systematically searched Clinicaltrials.gov, Ovid Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Scopus, Web of Science, and the World Health Organization’s ICTRP registry following an a priori protocol. Randomized controlled trials and observational studies involving patients supported on ECMO that compared antithrombin supplementation to no supplementation or placebo were included. Risk of bias was assessed with the Cochrane Risk of Bias 2 Tool for randomized trials and the Newcastle Ottawa Scale for non-randomized trials. Outcomes assessed included hemostatic events and mortality. Meta-analysis was performed using a random-effects model with the Mantel-Haenszel method for binary outcomes. Odds ratios (OR) with 95% confidence intervals were calculated.


Results: After screening 1,395 search results, eleven studies (10 observational, 1 randomized trial) involving 19,239 patients (18,649 pediatric and 590 adults) met inclusion criteria. The risk of bias was assessed to be low to some concerns across included studies. In meta-analysis, antithrombin supplementation was associated with no difference in bleeding (OR 1.38, 95% CI 0.88-2.17), thrombosis (OR 1.57, 95% CI 0.84-2.90), or mortality (OR 1.21, 95% CI 0.81-1.81), though there was considerable to substantial heterogeneity. In subgroup analysis, antithrombin supplementation in pediatric patients was associated with greater odds of bleeding (OR 1.29, 95% CI 1.00-1.68) and thrombosis (OR 1.70, 95% CI 1.51-1.91) compared to no supplementation.


Conclusions: Routine supplementation of antithrombin during ECMO was not associated with impact on hemostatic events or mortality compared to no antithrombin or placebo. In pediatric patients, antithrombin supplementation was associated with greater odds of bleeding and thrombotic events.