Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation

Table 3 Summary of studies reporting on argatroban in adult patients supported with extracorporeal membrane oxygenation

First author, Year	Study type	Population	Circuit (VA/VV)	CRRT	Bolus dose	Initial infusion	Monitoring	Duration	Majorbleeding	Thrombosis	Other adverse events	Outcome
Sin et al[37], 2017	Case report	27M ARDS, HIT	VV	Yes	NA	0.2 µg/kg/min	aPTT 50-60 s	60 d	Hemothorax developed while on heparin, resolved on ARGA day 27	None	Transient elevations in liver enzymes, no clinical consequence	Patient transferred for lung transplantation
Ratzlaff et al[35], 2016	Case report	58M ARDS, HIT	VV	No	NA	0.1-0.3 µg/kg/min	aPTT 60-90 s	11 d	None	None	NA	Withdrawal of care after 28 d of ECMO support
Johnston et al[34], 2002	Case report	32M CS, HIT	VA	No	10 mg	2 µg/kg/h	ACT 200-400 s aPTT 80-90 s	7 d	None	NA	NA	Decannulated on ECMO day 10
Dolch et al[32], 2010	Case report	40M ARDS, HIT	VV	No	NA	0.35 µg/kg/min	aPTT 45-60 s	108 d	Major bleeding after lung transplant (ECMO day 114) – ARGA held	NA	Hepatic failure post-transplant Infusion reduced to 0.02 µg/kg/min	Patient underwent lung transplant on ECMO day 114, complicated by graft failure Died on post-operative day 17 (multi-organ failure)
Fernandes et al[33], 2019	Case report	44M CS, HIT	VA	Yes	NA	1.5 mg/h	aPTT 60-70 s	20 d	Mediastinal bleeding due to pulmonary edema Massive intraoperative hemorrhage during LVAD insertion, DIC	LV and RV thrombus during intraoperative DIC	NA	Survived to discharge
Cornell et al[31], 2007	Case series	n = 4 with HIT ARDS (n = 3) CS (n = 1)	VA (n = 2) VV (n = 2)	No	NA	0.2-2.0 µg/kg/min	ACT 210-230 s	88-184 h	Major bleeding (n = 2)	NA	NA	Survival to discharge (n = 2, 50%) Death (n = 2, 50%)
Beiderlinden et al[30], 2007	Case series	n = 9 with ARDS, HIT	VV	n = 8	NA	2.0 µg/kg/min (n = 1) 0.2 µg/kg/min (n = 8)	aPTT 50-60 s	4 ± 1 d (mean)	Major bleeding (n = 1) in patient who received higher initial infusion dose	None	NA	Survived (n = 6) Died (n = 3)
Rougé et al[36], 2017	Case series	49M CS, HIT 69M ARDS, HIT	VA	n = 1	NA	0.2 µg/kg/min 1 µg/kg/min	aPTT 1.5-3.0 × baseline	10 d 8 d	NA	Circuit clotting (n = 1)	ALF requiring dose reduction	Survived (n = 1) Decannulated, but died prior to discharge (n = 1)
Menk et al[38], 2017	Retrospective	n = 34 ARDS, HIT or heparin resistance	VV (n = 24) pECLA (n = 9)	NA	NA	0.3 µg/kg/min	aPTT 50-75 s	265 h (131-460)	n = 11—no differences compared to matched UFH cohort	n = 6—no differences compared to matched UFH cohort	NA	n = 21 (54%) died

ACT: Activated clotting time; aPTT: Activated partial thromboplastin time; ARDS: Acute respiratory distress syndrome; ARGA: Argatroban; CRRT: Continuous renal replacement therapy; CS: Cardiogenic shock; DIC: Disseminated intravascular coagulation; ECLS: Extra-corporeal life support; HIT: Heparin-induced thrombocytopenia; LVAD: Left ventricular assist device; NA: Not available; TEG: Thromboeslastography; UFH: Unfractionated heparin; VA: Veno-arterial; VV: Veno-venous.