Anticoagulation during extracorporeal membrane oxygenation (ECMO) remains challenging. Direct thrombin inhibitors such as argatroban are increasingly proposed as alternatives to unfractionated heparin (UFH). We sought to characterize the dose titration and monitoring reliability of argatroban compared with UFH in adult patients who received ECMO.

This prespecified subanalysis of a randomized controlled pilot trial (2021-2024) included 40 adults on venovenous or venoarterial ECMO randomized to argatroban (target diluted thrombin time 0.6-0.8 μg/mL; n = 20) or UFH (target anti-factor Xa 0.2-0.3 IU/mL; n = 20). The primary outcome was the pooled proportion of measurements within the therapeutic target range. Secondary outcomes included dose requirements, time to target, dose-assay correlations, and platelet count trajectories.

Patients who were treated with argatroban achieved therapeutic targets significantly less often than those receiving UFH (38% vs 51% of pooled active measurements; P < .001). The median argatroban dose required to reach the initial target was 0.40 μg/kg/min (interquartile range, 0.34-0.49). Correlations between anticoagulant dose and monitored effect were weak-to-moderate for both agents (repeated measures correlation coefficient = 0.29 for argatroban vs diluted thrombin time, and repeated measures correlation coefficient = 0.31 for UFH vs anti-Xa). Both groups experienced a comparable decrease in platelet counts.

In this hypothesis-generating subanalysis, patients receiving argatroban achieved therapeutic targets less reliably than those receiving UFH. However, this variability likely reflects challenges in dosing strategy optimization and differing target stringencies rather than intrinsic pharmacokinetic instability of the drug.