Flow Effects on Coagulation and Thrombosis

Abstract

Abstract-Thrombosis occurs in a dynamic rheological field that constantly changes as the thrombus grows to occlusive dimensions. In the initiation of thrombosis, flow conditions near the vessel wall regulate how quickly reactive components are delivered to the injured site and how rapidly the reaction products are disseminated. Whereas the delivery and removal of soluble coagulation factors to the vessel is thought to occur via classic convection-diffusion phenomena, the movement of cells and platelets to the injured wall is strongly augmented by flow-dependent cell-cell collisions that enhance their ability to interact with the wall. In addition, increased shear conditions have been shown to activate platelets, alter the cellular localization of proteins such as tissue factor (TF) and TF pathway inhibitor, and regulate gene production. In the absence of high shearing forces, red cells, leukocytes, and platelets can form stable aggregates with each other or cells lining the vessel wall, which, in addition to altering the biochemical makeup of the aggregate or vessel wall, effectively increases the local blood viscosity. Thus, hemodynamic forces not only regulate the predilection of specific anatomic sites to thrombosis, but they strongly influence the biochemical makeup of thrombi and the reaction pathways involved in thrombus formation. T hrombosis is thought to begin with an event such as plaque rupture, vessel damage, or dysfunctioning endothelium, resulting in the exposure of active tissue factor (TF) on the vessel wall. 1 The exposed TF binds circulating factor VII/VIIa (fVII/fVIIa) with high-affinity (Kd Ͻ10 pM), forming a reactive vessel surface that proteolytically cleaves fIX and fX. The rate of this surface-bound reaction depends not only on biochemical factors (number and surface density of TF:VIIa complexes, intrinsic kinetic activity, and local phospholipid composition 2 ) but on the rate at which the substrates fIX and fX are transported by the flowing medium to the reactive surface 3 and the rate at which product is removed. 4 Moreover, the local accumulation of reaction product may be critical in overpowering endogenous inhibitors and successfully initiating coagulation.Although convective flow forces dominate the axial movement of blood components (coagulation factors, platelets, red cells, leukocytes, and inhibitors) throughout most of the body, in the few microns approaching the vessel wall where thrombosis is thought to initiate, the frictional drag of the vessel wall causes the axial flow velocity to slow to 0, and the convective and diffusive motion of blood components becomes comparable. 5 In this initial coagulation reaction, blood flowing parallel to the wall convectively transports coagulation factors (fIX and fX) from upstream to a region close to the reactive site, and Brownian motion mediates the radial movement toward the reactive wall. In the case of platelets adhering to the wall, a similarly defined adhesion rate is often inferred. 6 The bound proteins fIX and fX become proteolyt...

Effect of leg exercises on popliteal venous blood flow during prolonged immobility of seated subjects: implications for prevention of travel‐related deep vein thrombosis

“…Current ÔflowÕ models examining how the processes of coagulation and thrombosis come together are limited, and investigating the dynamic ÔflowÕ environment continues to remain a challenge [28].…”

Wall shear stress exposure time: a Lagrangian measure of near-wall stagnation and concentration in cardiovascular flows

“…Intravascular thrombosis is another compelling pathology associated with most cardiovascular diseases where near-wall transport becomes important [7,25]. The trajectories of individual platelets and the accumulation and residence time of chemical solutes including ADP, thrombin, and various blood factors control clot formation.…”

“…The local transport of several substances near and at the vessel wall are known to influence atherosclerosis progression [56]. For example, previous studies have looked into transport of low density lipoproteins (LDL) [17,20,30,14], high density lipoproteins (HDL) [40,24], oxygen [16,27], nitric oxide (NO) [45,35], monocytes [12,14], and adenine triphosphate ATP and adenine diphosphate ADP [13,15,8] as important mass transport processes involved in atherosclerosis.Intravascular thrombosis is another compelling pathology associated with most cardiovascular diseases where near-wall transport becomes important [7,25]. The trajectories of individual platelets and the accumulation and residence time of chemical solutes including ADP, thrombin, and various blood factors control clot formation.…”

Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC)

“…It was observed that the infusion of Tan IIA induced a decrease in PT and APTT when compared to the LPS control group. Platelet aggregation is one of the important triggers of blood coagulation in the pathologic thrombosis associated with DIC [15] . DIC produces massive thrombin, stimulates platelet aggregation and triggers the blood coagulation cascades.…”