BACKGROUND: We systematically analyzed the synergistic effect of: i) cytokine-mediated inflammatory activation of endothelial cells (ECs), and ii) shear-mediated platelet activation (SMPA) as a potential contributory mechanism to intraventricular thrombus formation in the setting of Left Ventricular Assist Device (LVAD) support. METHODS: Intact and shear-activated human platelets were exposed to nonactivated and cytokine-activated ECs. To modulate the level of LVAD-related shear activation, platelets were exposed to shear stress patterns of varying magnitude (30, 50, 70 dynes/cm(2), 10min) via a Hemodynamic Shearing Device. ECs were activated via exposure to inflammatory Tumor Necrosis Factor-α (TNF-α, 10 and 100 ng/mL, 24h), consistent with inflammatory activation recorded in patients on LVAD circulatory support. RESULTS: Adhesivity of shear-activated platelets to ECs was significantly higher than that of intact/unactivated platelets, regardless of the initial activation level (70 dynes/cm(2) shear-activated platelets vs. intact platelets: +80%, p