The Effects of Flow on Blood Coagulation and Thrombosis

Abstract

Both hemostasis and its pathological correlate. thrombosis. are dynamic events. That is. the various biochemical mechanisms that determine the extent of thrombosis at a particular site of injury depend on the local supply of reactive materials (cells and zymogens) and the senlor-a1 of the subsequent products (activated cells and enzymes). There is a rapidly growing literature indicating that the local fluid dynamic con-ditio~ls influence not only the quantity of blood elements which deposit but also the quality or type of deposit. For example, it has long been known that thrombi that form in arteries differ significantly from those that form 011 the venous side with respect to platelet, red cell and fibrinaceous content. However. the intravascular mechanisms underlying such differences have not been fully delineated. More recently, it has been realized that the phi-sical forces to which blood and vascular cells are exposed under physiological conditions may well alter the reactivity of these elements in flowing blood. For example. platelets exposed to physiologic shear forces in various types of viscometers (i.e.. devices that produce a uniform shear force throughout the test fluid) will aggregate without the addition of exogenous agonists. The mechanism by which shear force is recognized and translated across a cell membrane is not kvell understood: in endothelial cells. shear forces have been sho\vn to activate potassium channels in the cell wall. thereby leading to the release of the vasodilator nitric oxide (1). Despite the apparent recogliition of flow as a primary contributor to thrombotic events. the properties of flowing systems are not broadly appreciated. The intentio~ls of this article are to 1) introduce the basic concepts of fluid dynamics essential for an understanding of the multifaceted role of Ao\\ in surface-mediated thrombosis: 2) examine current hypotheses es regarding the mechanism(s) by which flow alters the activity ty of blood and vascular components: 3) briefly review the extensive evidence demonstrating that selected hemostatic defects are intrinsically dependent on flow; and 1) discuss how flow through regions of stenosed vessels. such as are present at sites of atherosclerotic lesions or during transient ischeluic attacks. may contribute to the severity of the disorder. Basic concepts of fluid dynamics Thrombosis at sites of vascular injury involves complex interactions between blood-borne elements. e.g., platelets and coagulation proteins. and constituents of the \ ascular wall. Blood flow constitutes an essential element of thrombotic

Acetylated Prothrombin as a Substrate in the Measurement of the Procoagulant Activity of Platelets: Elimination of the Feedback Activation of Platelets by Thrombin

“…It is not clear to what extent such platelets are activated in vivo by the ordinary hemostatic pathway and initiated by exposure of the subendothelium and to what extent by other causes, such as exposure to shear stress (1,2). It is known, however, that mechanical stress can activate platelets, and this is particularly relevant to studies of the effects of biomedical devices-chiefly prosthetic valves-on platelets and the increased thrombotic risk in patients with such valves (3,4).…”

Spatio-temporal Flow Analysis in Bileaflet Heart Valve Hinge Regions: Potential Analysis for Blood Element Damage

“…The temporal averaging of the spatially averaged velocity and RSS, along with the estimation of the exposure times as the hinge transit times, enables the comparison of the averaged loading on the blood elements crossing the hinge region with previously published blood damage shear stress thresholds. [1][2][3][4][5][6][7][8][9]12,[16][17][18][21][22][23][24][25][28][29][30][31][32][33][34][35]37 We first analyze the spatially averaged dynamics focusing on the influence of implant location and hinge design. We then discuss the results with respect to previously published models of blood damage based on stress and exposure time, together with rough estimates of viscous stress levels.…”

“…Figure 9 shows the RSS levels and estimated viscous stresses as a function of the transit time for each characteristic region for both leakage and forward flow phases. Also included are previously reported threshold levels for platelet activation 1,3,4,8,9,28,29,35 and hemolysis. 2,[5][6][7]12,[16][17][18][21][22][23][24][25][30][31][32][33][34]37 Figure 9 clearly indicates that the estimates of RSS and viscous stress levels along with their estimated exposure times are mostly below the established threshold levels.…”

In vitro platelet adhesion to endothelial cells at low shear rates during copper deficiency in rats

“…Shearing forces which exist when blood flows through blood vessels are known to directly activate platelets, resulting in the release of proaggregatory mediators and the expression of adhesion molecule binding sites [1][2][3][4]. von Willebrand factor (vWF) is one of the most important and specific of the adhesive proteins involved in the binding of activated platelets to the vessel wall.…”

“…This leads to the release of the vasodilatory and antiaggregatory agent nitric oxide (NO) [4,11], and of prostacyclin (PGI 2 ), which is an inhibitor of platelet aggregation [12] and inhibits platelet adhesion to the subendothelium [13]. Both stretching and shearing forces have been shown to cause enhanced prostacyclin (PGI 2 ) production in cultured endothelial cells [14].…”