Potential fluid mechanic pathways of platelet activation

Abstract

Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport.

Fig. 1

Stenosis profile and physiologic volumetric inflow waveform.

Fig. 2

Velocity (left) and strain rate (right) fields at equally-spaced times in the cycle. Velocity vectors are shown at a random sampling (< 1%) of the nodes.

Fig. 3

Cross-section of the activation potential field near the stenosis. Location in reference to vessel is shown upper-right and vertical axis in each plot is scaled ×2.

Fig. 4

AP field for a 2D simulation (top left) and extracted structures (top right). The proximal structure is dominated by shear but also separates flow that accumulates near the apex, as shown for the 3D simulation in the bottom row. The starting locations of two groupings of particles (appearing as one point due to their proximity) are initially divided by the proximal structure in 3D AP field (bottom left). The later locations are plotted after 1 cardiac cycle of time had elapsed.