Direct versus indirect thrombin inhibition during extracorporeal membrane oxygenation support for covid-19

ABSTRACT

Purpose: Anticoagulation during extracorporeal membrane oxygenation (ECMO) for COVID-19 can be carried out by direct or indirect thrombin inhibition. The former agent obviates monitoring of antithrombin III but differences in outcomes with either approach are uncertain. Methods: A retrospective, multi-center study was conducted. Adult patients (≥18 years old) placed on ECMO for severe respiratory or circulatory failure due to COVID-19 between March 1, 2020, to April 30, 2021, in the United States were included. Patient were divided in 2 groups based on the utilized anticoagulation agent during ECMO support 1) direct thrombin inhibitor (DTi, e.g. bivalirudin and argatroban) and 2) indirect thrombin inhibitor (IDTi, e.g. unfractionated heparin). The primary outcome was in-hospital mortality after ECMO placement assessed by a time-to-event analysis. Results: Overall, 455 patients from 17 centers were placed on ECMO, of whom 44 were excluded due to no reported anticoagulation agent. DTi was used in 160 (age 47±11, 28% female) cases and 251 patients received IDTi (age 47±12, 29% female). At 90 days, in-hospital mortality was 50% (DTi) and 61% (IDTi), p=0.08, (Figure). After adjustment for clinical covariates, the likelihood of in-hospital mortality was similar with DTi (aHR 0.79, 95%CI 0.57-1.10, p=0.16) compared to IDTi. Noted prevalence of deep vein thrombosis (DTi 14%, IDHi 12%), ischemic stroke (DTi 2%, IDHi 3%), intracranial hemorrhage (DTi 11%, IDHi 10%) and bleeding requiring transfusion (DTi 71%, IDHi 83%) was comparable between groups. Conclusion: Anticoagulants that directly or indirectly inhibit thrombin are associated with similar outcomes during ECMO for COVID-19.