Argatroban as an alternative to heparin in extracorporeal membrane oxygenation circuits

Abstract

We investigated the anticoagulant effects of argatroban, a direct thrombin inhibitor, versus heparin in extracorporeal membrane oxygenation (ECMO) circuits. Three sham circuits were prepared according to our hospital's standard practice and run for six hours simultaneously. Two circuits were anticoagulated with argatroban (one with heparin in the wet prime and one without). One circuit had heparin in the initial prime and was then anticoagulated with heparin. We measured thrombin generation (prothrombin fragment 1+2, D-dimer and thrombin-antithrombin complexes), activated clotting times (ACTs) and partial thromboplastin times (aPTTs), and monitored thrombus formation using thromboelastography. ACTs were >1000 s in each circuit throughout assessment. No clot initiation was detected by thromboelastography. Thrombin generation was decreased in circuits anticoagulated with argatroban versus heparin, despite aPTTs being less prolonged. These results suggest that argatroban may be more efficacious than heparin for anticoagulation in ECMO. Additional studies are warranted to further evaluate argatroban in this setting.

A Case Series Describing the Use of Argatroban in Patients on Extracorporeal Circulation

“…Several case reports describe the use of argatroban as an anticoagulant in extracorporeal circulation [1][2][3][4][5][6][7][8][9] and experimental models of extracorporeal circulation. 10,11 Our objective was to examine the use of argatroban as an alternative to heparin for systemic anticoagulation during ECLS. To our knowledge, we report the largest case series of patients who received argatroban for anticoagulation while on ECLS.…”

Overview of Pharmacological Considerations in Extracorporeal Membrane Oxygenation

“…The authors concluded that argatroban may be a more efficacious anticoagulant in this setting; however, this study should be considered hypothesis generating. 63 In another study, argatroban was demonstrated to be safe and effective for patients with suspected heparin-induced thrombocytopenia who were receiving venovenous ECMO for treatment of acute respiratory distress syndrome. Investigators found that patients had a 10-fold decrease in argatroban requirement (mean dose of 0.15 μg/kg per minute) compared with the dose recommended in the manufacturer's labeling.…”

Anticoagulation for Extracorporeal Life Support

“…Pharmacokinetics can be unpredictable due to factors affecting AT activity, variable metabolism rates, and other heparin-neutralizing proteins in the circulation. 8 At times it may be necessary to monitor and replace AT with AT concentrate or fresh frozen plasma (FFP). This becomes especially important in infants with who have developmental hemostasis and lower levels of AT.…”