This strategy maintained adequate anticoagulation during the entire period of hypothermic CPB; bleeding variables were not reported. Despite the reported bene ts of higher heparin dosing, other studies seemingly contradict these results. In a small prospective trial of 21 patients, Gravlee and colleagues [20] concluded that subclinical plasma coag- ulation occurs during CPB despite heparin concentra- tions greater than 4.1 IU/mL. Furthermore, postoperative mediastinal chest tube drainage correlates with increased heparin concentration, especially if hep- arin rebound is not carefully monitored. A subsequent, prospective study of 63 patients by Gravlee and col- leagues [21] showed that subjects who received an unfractionated heparin bolus of 400 IU/kg and had heparin concentration maintained greater than 4 IU/mL did not differ in mediastinal drainage or transfusion products from a control group of patients receiving a bolus dose of 200 IU/kg plus additional heparin for ACT values less than 400 seconds. A prospective trial in 31 patients undergoing cardiac surgery revealed that all patients had a residual circulating heparin level after protamine administration (mean 0.18 IU/mL), detected by a chromogenic anti-Xa assay. This residual heparin concentration did not correlate with ACT or whole blood heparin concentration nor did it correlate with post- operative mediastinal tube drainage volume [22]. Although the studies supporting higher unfractionated heparin doses are greater in size and number, the impact of using higher doses of heparin on postoperative bleeding appears to be unclear, especially if residual effects of heparin are not detected or treated. Documented therapeutic anticoagulation treatment of patients having CPB is necessary and is routinely per- formed using an ACT. However, ACT devices vary considerably in their measurement platforms, activators, sample volumes, and sensitivities to external elements such as hemodilution, hypothermia, and concomitant drug therapies [23, 24]. 