Blood surface interfacing that occurs within the extracorporeal membrane oxygenation (ECMO) circuit initiates contact activation, an important hemostatic pathway initiated by the Hageman factor, also called factor XII. Factor XII was first discovered in 1968, when Mr. Hageman, the index patient for factor XII deficiency, fractured his left hemi-pelvis after falling from a ladder.¹  On the twelfth hospital day, he suffered a massive pulmonary embolism and died. These episodes and current research suggest that Hageman factor or factor XII is not essential for intravascular coagulation, but its main roles lie in other physiologic processes.²  Activated factor XII is an essential protease in the kinin–kallikrein system. When plasma is exposed to nonendothelial surfaces, like the tubing in an ECMO circuit, factor XII becomes activated, initiating kallikrein activation and subsequent cleavage of high-molecular-weight kininogen, ultimately releasing bradykinin. The role that these mediators play in thrombo-inflammatory pathways in ECMO patients remains…