Arterial Thrombosis

Human blood platelets are known to play crucial roles in hemostatic and thrombotic events in the human vascular system. Platelet adhesion to injured tissue and platelet-platelet binding (aggregation) constitute important defenses against bleeding. However, these same reactions in some circumstances result in thrombotic and embolic interruption of blood supply.

Arterial thrombosis (myocardial infarction and stroke) are the leading causes of death in the Western world. Platelet activation is known to cause release of materials which promote development of atherosclerosis, and platelet aggregation is often the final event of arterial occlusion.

Our work, in collaboration with colleagues from the Texas Medical Center, has shown that flow conditions play an important role in determining platelet reactions. The shear stress field associated with flow in blood vessels can lead to stimulation, functional alterations, and lysis of platelets. Also, it is clear that both the rates and the extent of response of platelets to various agonists depend heavily on the shear field. Thus, studies in carefully controlled, known shear fields are particularly significant in elucidating the mechanics and kinetics of platelet reactions.

We have developed several controlled-shear reactors for studying platelet reactions. A rotational viscometer is fitted with fiber-optic probes which make it possible to monitor optical events indicative of platelet aggregation, secretion, and increase in intracellular calcium ion concentrations. Studies in these reactors use a variety of specific inhibitors and pathologic platelets with specific deficiencies to elucidate the mechanisms of platelet reactions. One long-term result of the work will be the development of improved anti-thrombotic agents.

David W. Chia /