In cases of severe cardiopulmonary failure, extracorporeal membrane oxygenation (ECMO) may be temporarily used as a life-saving support for cardiac and/or lung function. Operating under non-physiological flow conditions, characterized by elevated shear rates and stagnant flow zones, there is an increased risk of inducing thrombosis, bleeding and hemolysis. Pinpointing the underlying mechanism triggering the onset of thrombus formation may aid development of device design, as well as management of anti-coagulation, benefiting patient outcome. Here we present a combined methodology enabling a multiscale understanding of thrombus development. Two thrombi collected from different ECMO circuits were analyzed by computational fluid dynamics (CFD), ultra small angle X-ray scattering (USAXS) and scanning electron microscopy (SEM). USAXS quantified the density and bulk alignment of fibrin, building the thrombus scaffold structure. SEM provided information on cellular morphology and surface fibrin structure, and CFD identified regions in the ECMO circuit with high thrombotic potential. Together, this combined approach was able to link local flow conditions and the structural growth of thrombi in ECMO circuits.