A heparin-like effect was recently described in infants, children, and adults receiving bivalirudin while supported on extracorporeal membrane oxygenation following cardiopulmonary bypass. This is most likely due to endogenous release of glycosaminoglycans from vascular endothelium and mast cells and is associated with longer duration of extracorporeal membrane oxygenation and an increased incidence of sepsis. Further investigation into this effect should include patients without recent cardiopulmonary bypass, exclude the presence of covalent antithrombin-heparin complexes, and employ a variety of different heparinases for thromboelastography. The phenomenon may partially explain the heterogeneity of anticoagulation requirements in patients on extracorporeal life support.