  Continuous-flow ventricular assist devices (VADs) have been an increasingly
common, life-saving therapy for advanced heart-failure patients, but elevate
the risk of thrombosis due to a combination of non-physiological hemodynamics
and synthetic biomaterials. Limited work has been done to address platelet
adhesion and aggregation on artificial surfaces under flow with sub-threshold
concentrations of weak agonists. We perfused a blood analog containing
hemoglobin-depleted red blood cells and fluorescently labeled platelets across
a titanium alloy (Ti6Al4V) and zirconia-toughened alumina (ZTA) surface at
shear rates of 400 and 1000 s-1. Upstream of the specimen, sub-threshold
concentrations of ADP were uniformly introduced at concentrations of 0, 5, and
10 nM. Time-lapse videos of depositing platelets were recorded, and the
percentage of the surface covered was quantified. Surface coverage percentages
at 400 s-1and 1000 s-1were compared for each concentration of ADP and material
surface combination. We observed a threshold concentration of ADP that
expedites platelet deposition that is dependent on both shear and material
surface chemistry. Additionally, we observed embolization when thrombus areas
exceeded 300{\mu}m2, which was dependent on the combination of shear, ADP
concentration, and material surface. This work is the first to simultaneously
examine the three key contributing factors leading to thrombotic events. Our
findings assist in considering alternative material choices constituting VADs
and the need to address material reactivity in assessing antiplatelet agent
tests.
