Argatroban anticoagulation for adult Extracorporeal Membrane Oxygenation: A systematic review

Background: Extracorporeal Membrane Oxygenation (ECMO) is an established method of circulatory support in critically ill patients. Heparin is the widely used anti-coagulation treatment for patients on ECMO in view of its features. Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin III (AT-III) deficiency may lead to sub-therapeutic anticoagulation with potentially serious consequences. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban and bivalirudin as main agents. We aimed to review the evidence supporting the effectiveness and safety of argatroban as a potential definitive alternative to heparin in the adult patient population undergoing ECMO support. Methods: A web based systematic literature search was performed in Medline (PubMed) and Embase from inception until June 18 th 2020. Results: The search identified 13 publications relevant to the target (4 cohort studies and 9 case series). Case reports and case series with less than 3 cases were not included in the qualitative synthesis. The aggregate number of argatroban treated patients on Extra Corporeal Life Support (ECLS) was n = 317. In the majority of studies argatroban was used as a continuous infusion without loading dose. Starting doses on ECMO varied between 0.05 and 2 μg/kg/min and were titrated to achieve the chosen therapeutic target range. The activated partial thormboplastin time (aPTT) was the anticoagulation parameter used for monitoring purposes in most studies, whereas some utilized the activated clotting time (ACT). Optimal therapeutic targets varied between 43-70 to 60-100 seconds for aPTT and 150-210 to 180-230 seconds for ACT. Bleeding and thromboembolic complication rates were comparable to patients treated with unfractionated heparin (UFH). Conclusions: Argatroban infusion rates and anticoagulation target ranges showed substantial variations. The rational for divergent dosing and monitoring approaches are discussed in this paper. Argatroban appears to be a safe and viable alternative to UFH in patients requiring ECLS. To establish an ideal dosing strategy, larger prospective studies on well-defined patient populations are warranted.