Relative effects of inhibition of platelet recruitment mediated by ADP. TXA2, and thrombin

Previous mathematical modeling of the concentrations of platelet-derived platelet-active species near a growing thrombus in heparin-anticoagulated whole blood suggested that thrombin may dominate this process, that ADP may be somewhat important, and that thromboxane A2 (TxA2) may be less important. Experimental observations in heparinized whole human blood at a wall shear rate of 1000 s^-1 using various inhibitors of thrombin confirmed thrombin's major role, even in the presence of heparin. A large fraction of its activity was attributable to the stabilization of the thrombus by locally formed fibrin, as was observed by inhibition of this process. The instability of the thrombi to flow and the microembolization of thrombus fragments from the tops of thrombi was deduced from the shape of the axial deposition curve, from the shape of the temporal deposition curve, and by direct microscopic observation. Inhibition of ADP-mediated platelet recruitment also resulted in a large reduction of platelet deposition on collagen. Inhibition of TxA2-mediated recruitment resulted in reduction of deposition that was due more to a reduced hydrodynamic stability of the growing thrombi than to a reduced level of platelet attachment to the surface or aggregate structures.