Platelet-Fibrin Deposition On Subendothelium In Conenital Bleeding Disorders

1981 ◽  
Author(s):  
H J Weiss ◽  
V T Turitto ◽  
H R Baumgartner
Keyword(s):  
Shear Rate ◽  
Venous Blood ◽  
Rabbit Aorta ◽  
Initial Contact ◽  
Bleeding Disorders ◽  
Fibrin Deposition ◽  
Shear Rates ◽  
High Shear Rates ◽  
Viii And Ix ◽  
Chamber Studies

In order to identify components of the blood which are important in hemostasis-thrombosis, and to clarify the hemostatic defect in patients with bleeding disorders, we have measured various parameters of platelet dimensions and fibrin deposition on everted de-endothelialized rabbit aorta in an annular chamber. Studies were done by drawing venous blood directly through the chamber at various shear rates; platelet-fibrin deposition was measured morphometrically. At high shear rates (2600 sec-1 and above) the defective adhesion observed in von Willebrand’s disease (vWD) and the Bernard-Soulier Syndrome (BSS) is due to a requirement of the F.VIII/vWF and GPI complex for the initial contact of platelets with the subendothelium. The defect is enhanced with increasing shear rate. Reduced thrombus stability is also seen in vWD. At a shear rate of 650 sec-1 perfusion of normal blood for 5-10 min results in 65-95% surface coverage with fibrin. Both fibrin deposition and platelet thrombus dimensions were markedly decreased in patients with severe deficiencies of factors VIII and IX (PTT 100-140 sec), in the BSS, and in a patient with deficient platelet binding of Va-Xa. In contrast, normal (or near-normal) values were obtained in patients with severe deficiencies of factors XI and XII (PTT 100-500 sec). Fibrin formation was normal or increased in thrombasthenia. These findings provide a basis for identifying important components of the hemostatic mechanism on physiologic surfaces in flowing blood and may explain why some patients with deficiencies of factor XI and XII do not bleed.

Upstream Thrombus Growth Impairs Downstream Thrombogenesis in Non-Anticoagulated Blood: Effect of Procoagulant Artery Subendothelium and Non-Procoagulant Collagen

1991 ◽  
Vol 65 (05) ◽  
pp. 596-600 ◽  
Author(s):  
Kjell S Sakariassen ◽  
Harvey J Weiss ◽  
Hans R Baumgartner
Keyword(s):  
Shear Rate ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Rabbit Aorta ◽  
Axial Position ◽  
Fibrillar Collagen ◽  
Fibrin Deposition ◽  
Clotting Factors ◽  
Shear Rates ◽  
Platelet Deposition

SummaryIn the present experiments we have investigated the influence of wall shear rate and axial position on platelet and fibrin deposition which results when flowing human non-anticoagulated blood is exposed to either non-procoagulant fibrillar collagen (human type III) or procoagulant subendothelium (rabbit aorta). Platelet adhesion, thrombus volume and fibrin deposition were morphometrically evaluated at axial positions of 1 and 13 mm following perfusions for 5 min at shear rates of 100, 650 and 2,600 s-1.An axially-dependent decrease of platelet adhesion (34-57%, p <0.01-0.05) and thrombus volume (57-80%, p <0.05) was observed on collagen at all shear rates. On subendothelium, an axially-dependent decrease was observed for platelet adhesion only at 100 s-1 (29% ; p <0.01) and for thrombus volume at shear rates of 650 s-1 and above (49-58%, p <0.01). Deposition of fibrin on subendothelium was axially decreased (16-42%, p <0.05) at all shear rates, while no significant axial differences were seen on collagen. However, substantially more fibrin was deposited on the subendothelium (p <0.05), and the upstream platelet adhesion and thrombus volume were lower than on collagen (p <0.05) at 100 s-1 and 650 s-1. The axially-dependent phenomena on the two surfaces are consistent with the concept of rapid-growing upstream thrombi which deplete the blood layer streaming adjacent to the surface of platelets, leading to decreased platelet deposition farther downstream. The observations suggest that deposition of fibrin is enhanced by subendothelial tissue factor, and that upstream depletion of clotting factors may lower the downstream deposition of fibrin, analogous to the depletion of platelets.

scholarly journals Platelet and Fibrin Deposition on Subendothelium: Opposite Dependence on Blood Shear Rate

1977 ◽  
Author(s):  
H.R. Baumgartner
Keyword(s):  
Shear Rate ◽  
Rabbit Aorta ◽  
Vessel Diameter ◽  
Fibrin Deposition ◽  
Roller Pump ◽  
Shear Rates ◽  
Perfusion Chamber ◽  
Controlled Flow ◽  
Induced Aggregation ◽  
Blood Elements

The rate of platelet deposition on subendothelium (adhesion + adhesion-induced aggregation) from anticoagulated blood is shear rate (~ v/d) dependent and thus increases with increasing blood flow velocity (v) and decreasing vessel diameter (d). To investigate concomitant fibrin deposition, subendothelium of rabbit aorta was exposed to native blood under controlled flow conditions (Schweiz. Med. Wschr. 106, 1367 (1976)). Native blood was circulated by a roller pump for 3 min from a carotid artery through an annular perfusion chamber (maintained at 37°c) into a jugular vein of a rabbit at flow rates of 5, 20 and 40 ml/min, producing wall shear rates at the exposed subendothelial surface of 500, 2000 and 4000 s-1, respectively. Subendothelium and adhering blood elements were immediately fixed by perfusion of glutaraldehyde avoiding any blood-air interphase. Platelet interaction with subendothelium and fibrin deposition were determined morphometrically. At a shear rate of 500, 2000 and 4000 s-1, 23±3, 43±4 and 66±3% (mean ± SE) of the surface were covered with platelets and 67±12, 26±12 and 10±4% with fibrin, respectively. The corresponding values for adhesion-induced aggregation were 12±3, 38±6 and 56±5% in native and about 4, 17±5 and 29±4% in citrated (15 mM) blood indicating that even a low citrate concentration inhibits adhesion-induced aggregation. Similar results were obtained with human blood drawn from a cubital vein.This is direct evidence that fibrin deposition on subendothelium predominates at low (veins), platelet adhesion and aggregation at high (arteries + small vessel) shear rates.

Comparison of antithrombotic efficacy between edoxaban, a direct factor Xa inhibitor, and fondaparinux, an indirect factor Xa inhibitor under low and high shear rates

2011 ◽  
Vol 106 (12) ◽  
pp. 1062-1068 ◽  
Author(s):  
Naoki Tsuji ◽  
Yuko Honda ◽  
Chikako Kamisato ◽  
Yoshiyuki Morishima ◽  
Toshiro Shibano ◽  
...  
Keyword(s):  
Shear Rate ◽  
Arterial Thrombosis ◽  
Factor Xa ◽  
High Shear ◽  
Shear Rates ◽  
Thrombosis Model ◽  
Perfusion Chamber ◽  
High Shear Rates ◽  
Antithrombotic Effects ◽  
Antithrombotic Efficacy

SummaryEdoxaban is an oral, direct factor Xa (FXa) inhibitor under late-phase clinical development. This study compared the antithrombotic efficacy of edoxaban with that of an indirect FXa inhibitor, fondaparinux, in in vivo venous and arterial thrombosis models and in ex vivo perfusion chamber thrombosis model under low and high shear rates in rats. Venous and arterial thrombi were induced by platinum wire insertion into the inferior vena cava and by application of FeCl3 to the carotid artery, respectively. The perfusion chamber thrombus was formed by blood perfusion into a collagen-coated capillary at 150 s-1 (low shear rate) and 1,600 s-1 (high shear rate). Effective doses of edoxaban that reduced thrombus formation by 50% (ED50) in venous and arterial thrombosis models were 0.076 and 0.093 mg/kg/h, respectively. In contrast, ED50 of fondaparinux in the arterial thrombosis model (>10 mg/kg/h) was markedly higher compared to ED50 in the venous thrombosis model (0.021 mg/kg/h). In the perfusion chamber thrombosis model, the ratio of ED50 under high shear rate (1.13 mg/kg/h) to that under low shear rate (0.63 mg/kg/h) for edoxaban was 1.9, whereas that for fondaparinux was more than 66. While the efficacy of fondaparinux markedly decreased in arterial thrombosis and in a high-shear state, edoxaban exerted consistent antithrombotic effects regardless of flow conditions. These results suggest that shear rate is a key factor in different antithrombotic effects between edoxaban and fondaparinux.

scholarly journals Platelet von Willebrand factor: evidence for its involvement in platelet adhesion to collagen

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1214-1217
Author(s):  
E Fressinaud ◽  
D Baruch ◽  
C Rothschild ◽  
HR Baumgartner ◽  
D Meyer
Keyword(s):  
Shear Rate ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Von Willebrand Disease ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Von Willebrand ◽  
Willebrand Factor

Although it is well established that plasma von Willebrand Factor (vWF) is essential to platelet adhesion to subendothelium at high shear rates, the role of platelet vWF is less clear. We studied the respective role of both plasma and platelet vWF in mediating platelet adhesion to fibrillar collagen in a parallel-plate perfusion chamber. Reconstituted blood containing RBCs, various mixtures of labeled washed platelets and plasma from controls or five patients with severe von Willebrand disease (vWD), was perfused through the chamber for five minutes at a shear rate of 1,600 s-1. Platelet-collagen interactions were estimated by counting the radioactivity in deposited platelets and by quantitative morphometry. When the perfusate consisted of normal platelets suspended in normal plasma, platelet deposition on the collagen was 24.7 +/- 3.6 X 10(6)/cm2 (mean +/- SEM, n = 6). Significantly less deposition (16 +/- 2.3) was observed when vWD platelets were substituted for normal platelets. In mixtures containing vWD plasma, significantly greater deposition (9 +/- 2.2) was obtained with normal than with vWD platelets (1 +/- 0.4) demonstrating a role for platelet vWF in mediating the deposition of platelets on collagen. Morphometric analysis confirmed these data. Our findings indicate that platelet, as well as plasma, vWF mediates platelet-collagen interactions at a high shear rate.

Observations of rapidly flowing granular-fluid materials

1985 ◽  
Vol 150 ◽  
pp. 357-380 ◽  
Author(s):  
Daniel M. Hanes ◽  
Douglas L. Inman
Keyword(s):  
Shear Rate ◽  
Granular Material ◽  
Volume Concentration ◽  
Yield Criterion ◽  
Internal Boundary ◽  
Similar Data ◽  
Shear Rates ◽  
Lower Shear ◽  
High Shear Rates ◽  
Entire Flow

The rapid shearing of a mixture of cohesionless glass spheres and air or water was studied in an annular, parallel-plate shear cell designed after Savage (1978). Two types of flow were observed. In the first type of flow the entire mass of the granular material was mobilized. At high shear rates the shear and normal stresses were found to be quadratically dependent upon the mean shear rate (at constant volume concentration), in general agreement with the observations of Bagnold (1954) and Savage & Sayed (1984), and the ‘kinetic’ theory of Jenkins & Savage (1983). The stresses were found to be weakly dependent on the volume concentration up to approximately 0.5, and strongly dependent above this concentration. For flows in which water was the interstitial fluid, the ratio of the shear stress to the normal stress was slightly higher (than in air), and the stresses at lower shear rates were found to be more nearly linearly related to the shear rate. It is suggested that these effects are contributed to by the viscous dampening of grain motions by the water. The second type of flow was distinguished by the existence of an internal boundary above which the granular material deformed rapidly, but below which the granular material remained rigidly locked in place. The thickness of the shearing layer was measured to be between 5 and 15 grain diameters. The stress ratio at the bottom of the shearing layer was found to be nearly constant, suggesting the internal boundary is a consequence of the immersed weight of the shearing grains, and may be described by a Coulomb yield criterion. A scaled concentration is proposed to compare similar data obtained using different-sized materials or different apparatus. An intercomparison of the two types of flow studied, along with a comparison between the present experiments and those of Bagnold (1954) and Savage & Sayed (1984), suggests that the nature of the boundaries can have a significant effect upon the dynamics of the entire flow.

The Simulation of Aggregated Colloids Under Flow

1992 ◽  
Vol 289 ◽  
Author(s):  
John R. Melrose
Keyword(s):  
Shear Rate ◽  
Large Scale ◽  
Shear Thinning ◽  
High Shear ◽  
Shear Rates ◽  
Rouse Model ◽  
High Shear Rates ◽  
Structural Breakdown ◽  
Large Scale Simulations ◽  
Low Shear

AbstractAn overview is given of theories of aggregates under flow. These generally assume some sort of structural breakdown as the shear rate is increased. Models vary with both the rigidity of the bonding and the level of treatment of hydrodynamics. Results are presented for simulations of a Rouse model of non-rigid, (i.e. central force) weakly bonded aggregates. In large scale simulations different structures are observed at low and high shear rates. The change from one structure to another is associated with a change in the rate of shear thinning. The model captures low shear rate features of real systems absent in previous models: this feature is ascribed to agglomerate deformations. Quantitatively, the model is two orders of magnitude out from experiment but some scaling is possible.

scholarly journals Shear Rate Moderates Community Diversity in Freshwater Biofilms

2004 ◽  
Vol 70 (12) ◽  
pp. 7426-7435 ◽  
Author(s):  
Alexander H. Rickard ◽  
Andrew J. McBain ◽  
Amy T. Stead ◽  
Peter Gilbert
Keyword(s):  
Shear Rate ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Bacterial Biofilm ◽  
Community Diversity ◽  
Rrna Gene ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Static Conditions ◽  
Freshwater Biofilms

ABSTRACT The development of freshwater multispecies biofilms at solid-liquid interfaces occurs both in quiescent waters and under conditions of high shear rates. However, the influence of hydrodynamic shear rates on bacterial biofilm diversity is poorly understood. We hypothesized that different shear rates would significantly influence biofilm diversity and alter the relative proportions of coaggregating and autoaggregating community isolates. In order to study this hypothesis, freshwater biofilms were developed at five shear rates (<0.1 to 305 S−1) in a rotating concentric cylinder reactor fed with untreated potable water. Eubacterial diversity was assessed by denaturing gradient gel electrophoresis (DGGE) and culturing on R2A agar. Fifty morphologically distinct biofilm strains and 16 planktonic strains were isolated by culturing and identified by partial 16S rRNA gene sequencing, and their relatedness was determined by the construction of a neighbor-joining phylogenetic tree. Phylogenetic and DGGE analyses showed an inverse relationship between shear rate and bacterial diversity. An in vitro aggregation assay was used to assess the relative proportions of coaggregating and autoaggregating species from each biofilm. The highest proportion of autoaggregating bacteria was present at high shear rates (198 to 305 S−1). The intermediate shear rate (122 S−1) selected for the highest proportion of coaggregating bacteria (47%, or 17 of a possible 36 coaggregation interactions). Under static conditions (<0.1 S−1), 41 (33%) of a possible 125 coaggregation interactions were positive. Few coaggregation (3.3%) or autoaggregation (25%) interactions occurred between the 16 planktonic strains. In conclusion, these data show that shear rates affect biofilm diversity as well as the relative proportions of aggregating bacteria.

scholarly journals Effect of blood flow on thrombin generation is dependent on the nature of the thrombogenic surface

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2206-2213 ◽  
Author(s):  
A Diquelou ◽  
S Lemozy ◽  
D Dupouy ◽  
B Boneu ◽  
K Sakariassen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Shear Rate ◽  
Plasma Levels ◽  
Thrombin Generation ◽  
Type Iii Collagen ◽  
Fibrin Deposition ◽  
Positive Correlation ◽  
Shear Rates ◽  
Fibrin Formation

We have investigated the influence of blood flow on thrombin generation, fibrin formation, and fibrin deposition on procoagulant and nonprocoagulant surfaces. Nonanticoagulated human blood was drawn for 5 minutes directly from an antecubital vein over stimulated endothelial cells expressing tissue factor and over human type III collagen fibrils, positioned in parallel-plate perfusion chambers. The shear rates at these surfaces were 50, 650, and 2,600 s-1. Deposition of platelets and fibrin was measured by morphometry. Thrombin and fibrin formation was determined by measuring prothrombin fragments 1 + 2 (F 1 + 2), thrombin-antithrombin III complexes, (T-AT) and fibrinopeptide A (FPA) in blood effluent from the perfusion chamber at the end of the 5- minute perfusion period. On procoagulant endothelial cells, the thrombi were primarily composed of fibrin. The fibrin deposition (81%, 21%, and 2% at 50, 650, and 2,600 s-1, respectively) and plasma levels of F 1 + 2, T-AT and FPA were shear rate dependent and highest at 50 s-1. There was a positive correlation between F 1 + 2 and T-AT and the fibrin deposition (P < .01). In contrast, the collagen surface triggered primarily thrombi that were composed of platelets. The platelet thrombi and plasma levels of F 1 + 2 and T-AT were also dependent on the shear rate, but highest at 650 and 2,600 s-1. F 1 + 2 and T-AT reached the same level as observed with procoagulant endothelial cells at the higher shear rates. There was a positive correlation between F 1 + 2 and T-AT and the platelet thrombus formation (P < .05), confirming the predominant role of platelets in thrombin generation. Thus, thrombin formation is strongly influenced by the blood flow, and this effect depends on the composition of the thrombogenic surface.

scholarly journals Procoagulant activity of endotoxin-treated human endothelial cells exposed to native human flowing blood

Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 729-733 ◽  
Author(s):  
M Clozel ◽  
H Kuhn ◽  
HR Baumgartner
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Shear Rate ◽  
Fibrin Deposition ◽  
Human Endothelial Cells ◽  
Cellular Activation ◽  
Shear Rates ◽  
Fibrin Formation ◽  
Cultured Endothelial Cells ◽  
Flowing Blood

Abstract It has been reported that cultured endothelial cells become procoagulant when exposed to endotoxin. This prompted us to investigate whether human endothelial cells treated with endotoxin could promote the generation of fibrin when exposed to human flowing blood. For this purpose we used a parallel-plate perfusion chamber in which confluent cultured endothelial cells from human umbilical veins were exposed for five minutes to directly drawn human nonanticoagulated blood, at wall shear rates of 100, 650, and 2600 sec-1. Fibrin deposition was assessed by morphometry. No fibrin deposition occurred on normal endothelial cells. In contrast, cells incubated with endotoxin for 4 or 18 hours induced fibrin deposition, but only at a shear rate of 100 sec-1. Since some extracellular matrix was exposed between the cells, we investigated whether extracellular matrix played a role in fibrin formation. When the endothelial cells incubated or not with endotoxin were removed by EDTA, the exposed extracellular matrix perfused with blood at 100 sec-1 supported platelet and fibrin deposition in both cases. This suggests that the effect of endotoxin on endothelial cells was not due to extracellular matrix alteration but only to cellular activation or secretion of procoagulant substances. We conclude that human endothelial cells treated with endotoxin can trigger fibrin formation and deposition at their surface when exposed to flowing blood at low shear rate.

scholarly journals Macroscopic rheology of non-Brownian suspensions at high shear rates: the influence of solid volume fraction and non-Newtonian behaviour of the liquid phase

2021 ◽  
Author(s):  
Patrick Wilms ◽  
Jörg Hinrichs ◽  
Reinhard Kohlus
Keyword(s):  
Liquid Phase ◽  
Shear Rate ◽  
Volume Fraction ◽  
Solid Volume Fraction ◽  
Shear Thinning ◽  
High Shear ◽  
Rate Dependency ◽  
Shear Rates ◽  
Liquid Phases ◽  
High Shear Rates

AbstractModelling the macroscopic rheology of non-Brownian suspensions is complicated by the non-linear behaviour that originates from the interaction between solid particles and the liquid phase. In this contribution, a model is presented that describes suspension rheology as a function of solid volume fraction and shear rate dependency of both the liquid phase, as well as the suspension as a whole. It is experimentally validated using rotational rheometry ($$\varphi$$ φ ≤ 0.40) and capillary rheometry (0.55 ≤ $$\varphi$$ φ  ≤ 0.60) at shear rates > 50 s−1. A modified Krieger-Dougherty relation was used to describe the influence of solid volume fraction on the consistency coefficient, $$K$$ K , and was fitted to suspensions with a shear thinning liquid phase, i.e. having a flow index, $$n$$ n , of 0.50. With the calculated fit parameters, it was possible to predict the consistency coefficients of suspensions with a large variation in the shear rate dependency of the liquid phase ($$n$$ n = 0.20–1.00). With increasing solid volume fraction, the flow indices of the suspensions were found to decrease for Newtonian and mildly shear thinning liquid phases ($$n$$ n ≥0.50), whereas they were found to increase for strongly shear thinning liquid phases ($$n$$ n ≤0.27). It is hypothesized that this is related to interparticle friction and the relative contribution of friction forces to the viscosity of the suspension. The proposed model is a step towards the prediction of the flow curves of concentrated suspensions with non-Newtonian liquid phases at high shear rates.

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