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Systemic anticoagulation with unfractionated heparin is standard of care for patients receiving extracorporeal life support (ECLS); however, an alternative anticoagulant may be necessary when challenges with heparin therapy arise. Evidence for alternative anticoagulation in ECLS patients is limited. This retrospective analysis evaluated the dosing and outcomes associated with bivalirudin use in 14 adult ECLS patients. Indications for bivalirudin included heparin-induced thrombocytopenia, heparin resistance, or persistent clotting or bleeding while on heparin. The median initial bivalirudin dose to achieve target activated partial thromboplastin time was 0.15 mg/kg/h (range 0.04-0.26 mg/kg/h). Dosing requirements increased by 75-125% when renal replacement was included. Median time on bivalirudin was 5.2 days (range 0.9-28 days). Five patients (36%) required a circuit change while on bivalirudin because of clotting or failing oxygenation, and four (28.6%) had bleeding significant enough to require either reduction in activated partial thromboplastin time goals or temporary holding of anticoagulation. Bivalirudin appears to be a potential option for adult patients on ECLS who are unable to receive or fail heparin therapy; however, the wide variation in dosing suggests the need for careful management.

Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) are the most commonly used assays, but on occasion, the thrombin time may be useful. Other coagulation assays such as the dilute thrombin time (dTT), chromogenic anti-IIa assays, and the ecarin clotting time (ECT) can be used. The intensity of anticoagulation with DTIs depends on the indication for use. For patients with HIT, the target aPTT is 1.5 to 3.0 and 1.5 to 2.5 times the patient's baseline value for argatroban and bivalirudin, respectively. DTI anticoagulation used during percutaneous coronary intervention can be measured using ACT. Both DTIs may cause an elevation in the international normalized ratio depending on their plasma concentration. This article will review the use of parenteral DTIs and related laboratory assays for assessing the anticoagulant effect of these drugs.

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