Human platelet aggregation by thimerosal. Functional and ultrastructural studies

Thimerosal, a sulfhydryl group inhibitor, produces in an aggregometer a decrease in optical density of normal platelet-rich plasma over a wide range of concentrations. Ultrastructural study shows that the decrease of optical density produced by thimerosal at low doses is due to a true platelet aggregation preceded by a release reaction, whereas the aggregometric curves recorded after addition of thimerosal at high doses can be attributed to marked alterations of platelet morphology. Electron microscopic study shows the presence of electron-dense material between plasma membranes after addition of a low dose, and the early rupture of membranes after a high dose. These findings support previous conclusions that thimerosal binds to plasma membranes. Thimerosal induces a release reaction, seen in ultrastructural study and revealed by measurement of 14C-serotonin release. Moreover, thimerosal-induced aggregation is independent of released ADP and of formation of intermediates of the arachidonate pathway. Thimerosal-induced platelet aggregation is inhibited neither by ADP removal nor by aspirin addition.