Shear stressinduced formation of platelet thrombi is inhibited by ethanol at its attainable concentrations after drinking. The effect of documented risk factors, however, cannot explain the preponderance of certain lesion types, stent designs, and implantation configurations for the development of these complications. But together with the growing use of stents, stent thrombosis, the most feared complication after stent implantation, has emerged as an important entity to understand and. Role of high shear rate in thrombosis sciencedirect.
A highshear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Diagnosis of deep vein thrombosis relies on imaging techniques such as. Blood clotting, or thrombosis, is an interesting biological application for computational fluid dynamics. For these fluids the slope of the shear stressshear rate relation is constant over the. Nov 15, 2004 as expected, at venous levels of shear rate 100 s1 neither of the agonists had any effect on thrombus formation since platelet adhesion does not depend on activation at these low levels of shear.
A general sheardependent model for thrombus formation ncbi. The transcription factor erg regulates a low shear stress. The primary factors contributing to stent thrombosis are inadequate stent deployment, incomplete stent apposition, residual stenosis, unrecognized dissection impairing blood flow, and noncompliance with dual antiplatelet therapy dapt. For these models to be used in biomedical applications such as the design of rotary blood pumps, however, they must first be experimentally validated for high shear. Effects of different shear rates on the attachment and detachment of. A contraves low shear 2 coaxial cylindrical type viscometer was used for measurements at shear rates of23, 262, and0o77 s1. Note that the shear rates outside of the corners return to a normal shear rate range of 4501,000s. This speaks in favor of a model where ma thrombosis occurs in regions adjacent to the wall that experience low shear rates hence high srmd. The range of shear rates covered by the proposed model encompass venous and arterial thrombosis, ranging from lowshearrate conditions in. Evaluation of a numerical thrombosis model for a high.
At this time, 1 million coronary stent implantations are performed each year in the united states. In a british study,7 25% of white and 22% of black people with suspected thrombosis were con. Guidance for the treatment of deep vein thrombosis and. For these models to be used in biomedical applications such as the design of rotary blood pumps, however, they must first be experimentally validated for high shear rates and complex geometries. The shear rate and corresponding shear stress have impacts on arterial thrombus formation. At the outlet, the zone of very low shear rates is even larger and directly located in the corner of the junction. Effects of shear rate and dose parameters were analyzed using general linear models, logistic regressions, and cox proportional hazards modelstechniques often used in multiparameter clinical studies. Reduced platelet cohesion was present at low shear rates with low plasma. The incidence of thrombosis in patients with sle is 2550fold higher than in the general population.
Local hemodynamic factors, low endothelial shear stress ess. The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. The role of highshear flow in the pathogenesis of thrombosis is particularly relevant under pathological conditions such as in stenosed, atherosclerotic arteries, where shear stress can increase. Coagulation clotting is different from arterial thrombosis and occurs with stagnant blood or with blood. Microfluidic thrombosis under multiple shear rates and.
Jun 11, 2009 existing numerical thrombosis models have previously been shown to be effective for low shear rates and simple geometries. Blood clotting where it shouldnt or when you dont want it to. Restenosis and thrombosis are potentially fatal complications of coronary stenting with a recognized multifactorial etiology. The role of high shear flow in the pathogenesis of thrombosis is particularly relevant under pathological conditions such as in stenosed, atherosclerotic arteries, where shear stress can increase.
In these instances, prophylaxis with low dose anticoagulation is effective. Shear stressrate shear stressrate gradient bent postcapillary venules low reynolds number. Coagulation clotting is different from arterial thrombosis and occurs with stagnant blood or with blood flow with very low shear rate. Major differences between arterial and venous thrombosis.
In contrast, as haematocrit increases, the effect of shear rate changes on blood viscosity becomes greater. Shen f, kastrup c, liu y and ismagilov r 2008 threshold response of initiation of blood coagulation by tissue factor in patterned microfluidic capillaries is controlled by shear rate, arteriosclerosis, thrombosis, and vascular biology, 28. Results the cross sectional study revealed an association between intraaneurysmal spontaneous thrombus volume and the ar of the aneurysm r 2 0. Deep vein thrombosis should be suspected in any patient who presents with unexplained extremity swelling, pain, warmth or erythema. Oct 19, 2017 in small vessels that permit only singlefile flow of rbcs, viscosity increases linearly. Oct 16, 2018 using a syringe pump bbraun, this mixture was perfused through a flow chamber. In particular, the effects of increasing concentration of platelets at the vessel wall and activation of platelets at this site increase the growth and stability of the thrombi which may result in a fatal narrowing of the arterial lumen. Both of these phenomena occur in regions of flow separation. A clinically useful high shear thrombosis test device should require a small blood volume, have a welldefined high shear rate, and not depend on soluble platelet agonists, which are not initially present in arterial thrombosis. Sources of circuit thrombosis in pediatric extracorporeal. Platelet binding to collagen under conditions of low shear stress is mediated by the platelets receptors gp vi and cd36, but is thought to be of lesser importance in vivo.
A arterial thrombosis occurs under high shear flow when platelet rich thrombi are formed around ruptured atherosclerotic plaques and damaged endothelium. Sources of circuit thrombosis in pediatric extracorporeal me. Deep vein thrombosis and its sequelae pulmonary embolism and postthrombotic syndrome are some of the most common disorders. Mcp 10 thrombosis lecture notes columbia university. B venous thrombosis occurs under low shear flow and mostly around intact endothelial wall.
For the inlet to the connector, a zone of very low shear rates less than 50s is present in the corner. Recirculation regions, very low shear stress areas, flow separation, sharp edges etc. Interestingly, at a shear rate of 2000 s 1 the addition of lname caused an increase in platelet coverage suggesting that shear, by itself. A general sheardependent model for thrombus formation. Red blood cells in thrombosis blood american society. Under low shear stress ss, ec express relatively low levels of klf2 and tm. Inhibition by ethanol of shear stressinduced formation of. As expected, at venous levels of shear rate 100 s1 neither of the agonists had any effect on thrombus formation since platelet adhesion does not depend on activation at these low levels of shear. The incidence rate of arterial thrombosis at 6 months was 4. Petit institute of bioengineering and biosciences, georgia institute of technology, 315 ferst dr. From a rheological point of view, liquids can be divided into two main groups fig. In particular, the effects of increasing concentration of platelets at the vessel wall and activation of platelets at this site increase the growth and stability of the thrombi which may result in. Evaluation of a numerical thrombosis model for a high shear.
Assessment of whole blood thrombosis in a microfluidic. Mechanical mechanisms of thrombosis in intact bent. Sep 26, 20 the cumulative rate of nonfatal thrombosis was 3. Platelet aggregation was evaluated by using a total thrombusformation analysis system, and shear rates of s. Novel stenotic microchannels to study thrombus formation. Pdf the impact of blood shear rate on arterial thrombus formation. Role of endothelial shear stress in stent restenosis and. The times required to generate increases in flow pressure of 10 kpa t10, 30 kpa t30 and 50 kpa t50 in microchips containing the blood, which depend on the degree of thrombus generation, were. This is because the initial adhesive interactions between platelets and the extracellular matrix depends on the local rheological conditions. Platelet binding to collagen under conditions of low shear stress is mediated by the platelets receptors gp vi and cd36, but is. A thrombus either arises spontaneously or is caused by clinical conditions including surgery, trauma, or prolonged bed rest.
Pain associated with dvt is often described as being a. This was the case for the vwf deficiency and the vwd subtypes investigated28,29. Microvascular adhesion of platelets to endothelium occurs in response to various inflammatory stimuli, and in venules is often accompanied by adherent leukocytes. Microvascular adhesion of platelets to endothelium occurs in response to various inflammatory stimuli, and in venules is often accompanied by. Red blood cells in thrombosis blood american society of. The invention of intracoronary stents greatly increased the safety and applicability of percutaneous coronary interventions. Definition of the hierarchical structure of thrombi by the extent of. Pdf determination of a shear rate threshold for thrombus. The prevalence of deep vein thrombosis in asian populations is low. This work represents a quantitative comparison of the effects of high shear rate and antiplatelet therapy dose on thrombosis. Role of high shear rate in thrombosis journal of vascular. Additionally, at low shear rates 54 sec1 haematocrit variations induce greater changes in blood viscosity.
Using a syringe pump bbraun, this mixture was perfused through a flow chamber. Fibrin deposition was decreased at all shear rates tested 28,31. Polymorphism gpia c807t increased platelet cohesion at high arte. The mechanistic link between these two parameters was further investigated through a fourier analysis of the intraaneurysmal shear rate sr obtained by computational fluid. The impact of blood shear rate on arterial thrombus formation. Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium. Mechanisms of thrombosis maureane hoffman, md, phd professor of pathology. Flow effects on coagulation and thrombosis citeseerx. Pain associated with dvt is often described as being a cramp or ache in the calf or thigh. For most physiological shear rate conditions 50 to 100s, the viscosity of whole blood is. Stent thrombosis carries a mortality rate of 20% to 45%. Erythrocyte concentration constitutes the primary determinant of blood viscosity because.
Thrombosis low shear rate triggers the formation of clots or thrombus. Collectively, compared with physiological low wsrs, pathological high wsrs. Method a cross sectional study on 21 patients was carried out to investigate the possible association between intraaneurysmal spontaneous thrombus volume and the dome to neck aspect ratio ar of the aneurysm. Platelet thrombus formation on the surface at lower 100 s1 and higher 2000 s1 levels of shear rate are shown in figures 3a,3b and 3e,3f respectively. This may simply result in low shear regions near the vessel wall and away from. A computational model capable of predicting deviceinduced thrombosis on a macroscopic scale and relatively quickly, compared to existing models, would be useful in the. The impact of blood shear rate on arterial thrombus formation ncbi. Deep vein thrombosis, commonly referred to as dvt, occurs when a blood clot or thrombus, develops in the large veins. Viscosity and retinal vein thrombosis british journal of. At sites of severe vessel narrowing, which may occur at sites of atherothrombosis, shear rates experienced by platelets can increase 12 orders of. Systemic lupus erythematosus sle is now a wellrecognized risk for thrombosis. A high shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood.
At the lower, venous shear rate 100 s1 platelet accumulation on the surface is not significantly altered by either insulin 500 pm or isoproterenol 100. At high arterial shear rates, transient deformation of rbcs reduces blood viscosity. Clots can grow in size, blocking the blood flow in the pump, or can even break off and be carried into the circulatory system. Awells brookfield coneplate microviscometer model lvt was used to measure viscosity at a shear rate of 230 inverse seconds s1. The range of shear rates covered by the proposed model encompass venous and arterial thrombosis, ranging from low shearrate conditions in abdominal aortic aneurysms and thoracic aortic dissections to thrombosis in stenotic arteries following plaque rupture, where local shear rates are extremely high. Existing numerical thrombosis models have previously been shown to be effective for low shear rates and simple geometries. With prompt diagnosis and treatment, the majority of dvts are not life threatening. Correlation of thrombosis growth rate to pathological wall shear rate during platelet accumulation. Interestingly, at a shear rate of 2000 s1 the addition of lname caused an increase in. Pdf the shear rate and corresponding shear stress have impacts on arterial thrombus. Determination of a shear rate threshold for thrombus. In patients with recent onset of sle, the incidence rate for thrombosis is 31 patients per year. Erg is essential for p300 recruitment and basal acetylation of histone h3 h3k27ac, a marker of open and accessible chromatin, and for klf2 binding to the tm promoter, and thus is required for basal tm expression in ec. Plateletderived no slows thrombus growth on a collagen type.
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