T he indications for the use of extracorporeal membrane oxygenation (ECMO) have expanded significantly from the early years of predominantly neonatal respiratory failure decades ago to current severe neonatal and pediatric cardiac and/or respiratory failure. Considerable advances in the materials and components used and the techniques used for the provision of extracorporeal support have been made over that same time period. However, the inability to completely control the interaction between blood and the biomaterials of the extracorporeal circuit, along with the subsequent inflammatory and coagulation response, still results in bleeding and thrombotic complications (1). Although a patient is receiving ECMO support, there is continuous contact between circulating blood and foreign surface of the extracorporeal circuit. As a result of this, the normal physiologic hemostatic balance is shifted to a hypercoagulable state, with patients, extracorporeal circuits and components at risk for thrombosis. In order to suppress hemostatic activation and prevent thrombosis, administration of antithrombotic therapy is necessary. Ideally, when using antithrombotic therapy for ECMO, platelet and coagulation factor activation should be inhibited enough to minimize clot formation in the ECMO circuit while maintaining enough endogenous procoagulant activity to avoid bleeding in the patient. However, this can be a difficult balance to sustain, and as a consequence, bleeding and thrombotic complications are not only some of the most common complications encountered during the provision of ECMO support but, more importantly, also associated with increased overall mortality (2-4).Unfractionated heparin (UNFH) is an antithrombotic agent and is the most widely used systemic anticoagulant during the provision of ECMO support. The activated clotting time (ACT) has been used for decades to monitor UNFH therapy in extracorporeal applications and remains the most commonly used test during ECMO to dictate UNFH dosage. The ACT is a low cost, point-of-care test (POCT), available 24 hours per day in most centers. Because of some potential shortcomings of UNFH and the ACT alone, including the effects of hemodilution, hypothermia, and the fact that different ACT devices can yield divergent results, it may be useful to complement regular whole blood ACT measurements, intermittently, with more elaborate tests of UNFH anticoagulation. To this end, alongside the technological evolution in extracorporeal life support, the methods for monitoring UNFH activity have also become more sophisticated, adding additional layers of complexity with a goal of creating an ideal safe protocol for anticoagulation during extracorporeal life support (5). In fact, a recent report of a survey of ECMO medical directors and coordinators at Extracorporeal Life Support Organization (ELSO) member centers revealed that although ACT was still the predominant method used to titrate UNFH for ECMO applications, there was concomitant use of other measures of UNFH anticoagulation, i...