Shear-induced platelet activation and receptor shedding in mechanical circulatory support (MCS) paradoxically increase risks of thrombosis and bleeding. Although flow cytometry commonly assesses platelet activation and receptor expression, correlations with structural changes remain poorly defined. Recent studies emphasize the role of the marginal band (MB) in platelet morphological transitions during activation. This study investigated MB alteration in shear-induced activated platelets and its relationship with flow cytometric markers. Human blood was circulated in a circulatory loop with an MCS device for 4 hours. Under three operating conditions from 75 to 350 mm Hg pressure head, platelet activation (PAC-1 and P-selectin) and glycoprotein (GP) receptor shedding (GPIbα, GPVI, GPIIb/IIIa) were quantified by flow cytometry, and the MB collapse state was microscopically examined and classified. Results demonstrated that platelet activation, receptor shedding, and MB collapse progressively increased with increasing pressure head in the loop. Marginal band collapse correlated strongly with platelet activation, but less with platelet receptor shedding. Marginal band collapse varied significantly among the population of activated platelets, highlighting the complex, heterogeneous response of platelets to shear stresses generated in the loop. The study suggested that the MB collapse can be used as an effective assay to examine platelet activation caused by MCS devices.