Fluid Mechanics of Blood Clot Formation

Abstract

Intravascular blood clots form in an environment in which hydrodynamic forces dominate and in which fluid-mediated transport is the primary means of moving material. The clotting system has evolved to exploit fluid dynamic mechanisms and to overcome fluid dynamic challenges to ensure that clots that preserve vascular integrity can form over the wide range of flow conditions found in the circulation. Fluid-mediated interactions between the many large deformable red blood cells and the few small rigid platelets lead to high platelet concentrations near vessel walls where platelets contribute to clotting. Receptor-ligand pairs with diverse kinetic and mechanical characteristics work synergistically to arrest rapidly flowing cells on an injured vessel. Variations in hydrodynamic stresses switch on and off the function of key clotting polymers. Protein transport to, from, and within a developing clot determines whether and how fast it grows. We review ongoing experimental and modeling research to understand these and related phenomena.

Platelets and hemostasis: a new perspective on an old subject

“…11,15 Studies performed in silico extend the observational studies and provide hypotheses that can be tested in vivo and in vitro. 10,16,17 Most of the studies summarized in Figure 1 were performed in the mouse microvasculature using a laser or a sharpened probe to make small holes in arterioles and venules. To what extent are the results applicable to people?…”

Counting and Tracking: Development and Use of New Methods for Detailed Analysis of Thrombus Formation

“…The flow rate is proportional to the shear stress (19). In blood circulation, the platelets are mainly found in proximity to the vessel wall and the red blood cells concentrated at the centre ( Figure 6) (19,56). This process, margination, subjects the platelets to the highest shear stress.…”

“…The shear rates described are estimated at the vessel wall, as this is where the highest concentration of platelets is. As previously mentioned, the platelet adhesion and aggregation are to some extent dependent on different mechanisms so that haemostasis may function independently of the prevailing shear rate (12,19,56,58,59). …”

“…2) An increase in flow transports platelets, agonists and coagulation factors to and from the site of injury or the atherosclerotic lesion. Such mass transfer may regulate the haemostatic response by limiting the possibility for the coagulation cascade to work properly and may also dilute such activators as thrombin and deliver inhibitors such as antithrombin, thereby restricting the coagulation response to the area of the platelet plug (56). The mass transfer thereby affects not only thrombus growth but also the stability, composition and risk of embolic or occlusive thrombotic events (60).…”

“…Over a certain shear rate (>10 000s -1 ), platelet aggregation can occur even without platelet activation (56). Stable platelet aggregation induced by shear may depend on the sequential acceleration and deceleration of the platelet before and after a stenosis and that the elevated shear itself is not the cause of the aggregation.…”