Argatroban Anticoagulation for Adult Extracorporeal Membrane Oxygenation: A Systematic Review

Abstract

Background: Heparin is the widely used anti-coagulation strategy for patients on extracorporeal membrane oxygenation (ECMO). Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin (AT) deficiency preclude the use of heparin requiring utilization of an alternative anticoagulant agent. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban as one of the main agents. We aimed to review the evidence with regard to safety and efficacy 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, 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 ECMO was n = 307. 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 and 60-100 seconds for aPTT and between 150-210 and 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 potential alternative to UFH in patients requiring ECMO. To definitively establish its safety, efficacy and ideal dosing strategy, larger prospective studies on well-defined patient populations are warranted.

Is bivalirudin an alternative anticoagulant for extracorporeal membrane oxygenation (ECMO) patients? A systematic review and meta-analysis

“…It concluded that argatroban appeared to be a feasible, effective and safe anticoagulant for critically ill ARDS patients undergoing extracorporeal lung support. A systematic review has similar findings [29] in adult patients on ECMO. A retrospective observational study [30] also indicated that argatroban was safe and useful in patients who were suspected of having HIT and were started on argatroban, but were ultimately found to have non-HIT.…”

Alternatives to heparin anticoagulation for cardiopulmonary bypass and extracorporeal membrane oxygenation

“…75 A recent systematic review included four cohort studies and 9 case series totaling 307 patients with the use of argatroban during ECMO. 76 A continuous infusion without a loading dose was used in the majority of cases, although infusion rates varied widely. aPTT was most often used for monitoring but without consensus targets.…”

“…Bleeding and thromboembolic complication rates were found to be comparable to those of patients who received UFH. 76 For argatroban, the SCA has issued a Class IIb recommendation for patients with renal failure and HIT who require CPB, with warning of increased bleeding risk. 11 Currently, the Extracorporeal Life Support Organization (ELSO) guidelines recommend consideration of the aforementioned three parenteral DTIs as alternative anticoagulants for patients with HIT.…”

Extracorporeal Membrane Oxygenation for Adults and Children With Severe Respiratory Failure

“…This has led to additional pressures on ECMO centres and highlighted the potential role of ECMO in the treatment of COVID-19. 3,4 The purpose of this report is to provide insights from the qualitative literature on the perspectives of those engaging with ECMO, including patients, their family, and their caregivers to support decision-making around the provision and delivery of ECMO for respiratory failure.…”

“…I question, what are we actually doing? Are we actually treating this person like a human being or is (the patient) becoming a lab experiment (p. [3][4]." 11 In this same study (evaluating the ethics consultation protocol), particular cases were evoked by clinicians during interviews.…”