Faculty Bibliography

When blood contacts foreign material surfaces, platelets usually adhere and form aggregates on those surfaces, generating mural thrombi. The mechanism of mural thrombogenesis is not completely understood, but one hypothesis states that the local release of certain platelet-active substances from the platelets composing an initial small thrombus stimulates additional platelet recruitment to that thrombus, resulting in growth of the cell aggregate. The purpose of this paper is to investigate the feasibility of this hypothesis. Concentration profiles of adenosine diphosphate (ADP), thromboxane A2 (TxA2), and thrombin were computed in the vicinity of growing model thrombi 10 and 20 micron long. Wall shear rates of 100, 500, and 1,500 s-1 were considered for blood flowing through a thin rectangular slit 200 micron wide coated with collagen, a predominant subendothelial protein. The local concentrations of ADP and TxA2 were marginally large enough to stimulate platelet activation individually, while local thrombin levels can be much greater than required for stimulation. Antithrombin III, a natural thrombin inhibitor, did not significantly reduce the thrombin concentrations, but antithrombin III accelerated by heparin greatly reduced the local thrombin concentrations. The reduced thrombin levels may, however, still be large enough to activate platelets.

Visualization and analysis of mural thrombogenesis on collagen-coated glass, polyurethane and nylon was discussed. Epi-fluorescent video microscopy was used to visualize thrombotic events at a protein or polymer surface in contact with flowing whole blood. Digital image processing was used to analyse the real-time microscopic images obtained, resulting in measurements of morphological features and the number of platelets that compose each thrombus. The three-dimensional structures of the thrombi were also estimated. A photodiode was used to measure integrated end-point platelet accumulation at different axial positions along the surface. Additionally, the convection-diffusion equations were solved to estimate the concentrations of adenosine diphosphate, thromboxane A2, and thrombin generated by activated platelets at the blood-contacting surface.