The establishment of a safe or optimal range for ACT dates back to data published in the 1970s when Bull and colleagues [3] showed no development of clot in the oxygenator or cir- cuit when ACT was maintained above 300 seconds. However, Young and coauthors [4] challenged this threshold when they demonstrated brin formation in the circuits of rhesus monkeys maintained on CPB with a minimum ACT value of 300 seconds, and they recom- mended that this threshold value be increased to 400 seconds by showing it was safe in 5 pediatric patients on 652 Ann Thorac Surg ANTICOAGULATION DURING CARDIOPULMONARY BYPASS 2018;105:650 62 REPORT CPB. To maintain a margin of safety above 400 seconds, the minimum acceptable ACT value of approximately 480 seconds became a standard of care that was used in numerous future studies and in clinical practice, but was based on limited evidence. Despite this widely accepted level of anticoagulation, there is no clear consensus on the accurate calculation of this initial dose of unfractionated heparin. Options for calculating the initial heparin bolus include a xed, weight-based dose, (eg, 300 IU/kg), or use of point-of-care tests that measure the whole blood sensitivity to heparin using an associated dose response. In addition to the heterogeneity of heparin formula- tions themselves, individual responsiveness to heparin is variable. The pharmacodynamics of unfractionated hep- arin are highly dependent on the level and function of plasma antithrombin III. In patients with preoperative hypercoagulability or reduced antithrombin III respon- siveness, increased levels of circulating heparin are necessary to achieve a therapeutic ACT value before CPB [5]. Na and coauthors [5] reported signi cant variations to heparin responsiveness in an observational study of pa- tients with known, stabilized infectious endocarditis. 