Extracorporeal Membrane Oxygenation (ECMO) is a complex technology used to support patients with severe respiratory and/or cardiac failures. Because blood contacts with foreign non-biologic surfaces that result in thrombus formation within the extracorporeal circuit, the management of patients placed on ECMO requires monitoring anticoagulation – heparin (UFH), which is used to balance between clot formation and bleeding difficulties. Though Activated Clotting Time (ACT), which is a test used to monitor high doses of unfractionated heparin therapy, is the preferred method of monitoring, it is imprecise and insensitive to lower dose (0.2-0.4 aXa U/mL) of heparin. The goal of this study was to evaluate the effects of other factors than heparin – hematocrit, coagulation factor levels, platelet count, contact activators, and antithrombin – on ACT and raise awareness of how the use of ACT in monitoring low dose UFH under ECMO support was controversial. Results of experiments showed when only antithrombin levels or heparin concentration increased, ACT values were prolonged but only for heparin concentration > 0.5 U/mL. Decrease in single factor change of coagulation factors, Factor XII, and platelet count led to rise in ACT results. However, no correlation was observed between ACT values and hematocrit changes (r² = 0.03). When different levels of all factors of interest and heparin were mixed together randomly, heparin concentration and ACT values didn’t show any correlation (r² = 0.00), suggesting the interference of other factors on its results. However, aXa heparin activity assay demonstrated a strong correlation (r² = 0.99) with heparin concentration even in multiple random factors change. Thus, further research should be performed to evaluate impacts of other factors in clinical relevance and aid in a change to the preferred method of monitoring low dose UFH under ECMO support.