Clinically, heparin concentration tests are performed alongside a functional test of clotting, such as an ACT, because a therapeutic functional con rmation of anticoagulation provides important safety data. In a randomized controlled trial of 200 patients, Koster and colleagues [13] found that adhering to a heparin con- centration maintenance protocol led to a signi cant reduction in thrombin generation, brinolysis, and neutrophil activation, when compared with ACT moni- toring alone (480 seconds). Despotis and associates [14] randomized patients to ACT-based (using 5,000 units unfractionated heparin doses to maintain ACT values >480 seconds) versus heparin concentration-based man- agement (with minimum ACT >480 seconds), and re- ported a higher heparin total dose in patients in the heparin concentration group (612  147 U/kg versus 462  114 U/kg, p < 0.0001). Patients in the heparin concen- tration group also had lower protamine to heparin ratios and required signi cantly fewer blood product trans- fusions (platelets, plasma, and cryoprecipitate) than the ACT-based control group. Another randomized trial of 31 patients scheduled for reoperation resulted in signi cant reductions in perioperative blood loss and blood product usage when maintaining higher patient-speci c heparin dosing during CPB [15]. Another study found reduced platelet activation and evidence of reduced thrombin generation with heparin concentration monitoring compared with routine ACT monitoring [16]. Together, these studies suggest that whole blood heparin concen- tration monitoring results in larger doses of unfractio- nated heparin during CPB and improved hemostatic suppression compared with ACT monitoring alone. However, these results did not translate into improved clinical outcomes and have not been wholly reproducible in the literature. A retrospective analysis involving 686 patients favored ACT-based monitoring compared with heparin concentration monitoring because of less post- operative bleeding and transfusion requirements associ- ated with ACT-based monitoring [17]. 