1993 WHITAKER LECTURE - BIORHEOLOGY IN THROMBOSIS RESEARCH

A review is presented on biorheological studies of platelet activation and platelet-platelet binding events that play key roles in thrombosis and hemostasis. Rheological methods have been used by a number of workers to establish the importance of fluid mechanical shear stress as a determinate of platelet reactions. Fluid mechanical shear stress can be regarded as a platelet agonist that is always present in the circulation and that is synergistic in its actions with other agonists. Early biorheological studies were phenomenological in that they focused on stress effects on measures of platelet function. Subsequent studies have elucidated mechanisms and have shown that the biochemical pathways of platelet activation are very different at elevated shear stresses than in the low shear stress environment used in many platelet activation studies. This finding that biochemical pathways of platelet activations are different at different shear stress levels suggests that it may be possible to develop platelet inhibitors of highly specific action: it may be possible to inhibit pathways important in thrombosis in a partially occluded artery without seriously compromising the normal hemostatic function of platelets. Another aspect of the work suggests that the biorheological approach may make it possible to develop better methods for prediction of thrombotic tendencies in human subjects.