Thrombolysis, flow, and vessel wall interactions

Abstract

Vascular endothelium remains a dynamic interface between blood, blood platelets, and the vessel wall. New developments make clear that many antithrombotic and prothrombotic responses of the endothelium depend on flow conditions in an adaptive manner: duration of a certain level of shear stress matters as well as level of shear. In general, over the course of several hours, endothelium appears to be more actively antithrombotic under moderate shear conditions (eg, 15 dyne/cm2) and more fibrinolytic under high shear conditions (eg, 30 dyne/cm2). Pulsatile flow and cyclic wall stress further modify these responses. Special consideration, moreover, must be given to branch points and regions of irregular geometry (ie, stenoses, aneurysms) in the circulation. In such locations-predilection sites for thrombosis, lipid uptake, and atherosclerosis-low levels of shear stress (eg, 0.5 dyne/cm2), large gradients in shear stress, and vessel wall bending stresses all become important. Preliminary work suggests that endothelial cells in such regions can become prothrombotic, leading to localized platelet adhesion/aggregation and fibrin formation on subendothelium and perhaps deeper structures following vessel injury. Flow effects on thrombolysis remain largely unstudied.