Tissue factor-induced coagulation triggers platelet thrombus formation as efficiently as fibrillar collagen at arterial blood flow conditions.

SummarySubendothelium of rabbit aorta and fibrillar collagen were exposed to citrated human or rabbit blood which was circulated through a perfusion chamber under flow conditions similar to those found in arteries. The resulting platelet adhesion and subsequent formation of platelet micro thrombi on the exposed surfaces were measured in 0.8 μm thick sections by a morphometry technique using light microscopy.Removal of plasma ADP by the substrate-enzyme combination CP-CPK (creatine phosphate-creatine phosphokinase; 3 mM and 90 U/ml blood) did not affect the initial attachment and spreading of platelets on subendothelium, whereas platelet thrombus formation was strongly inhibited. On free collagen fibrils CP-CPK was much less inhibitory on platelet thrombus formation but platelet adhesion again was not affected. It is concluded that platelet aggregation induced by thrombogenic surfaces in the presence of arterial blood flow is at least partially governed by ADP released from adhering platelets. Platelet adhesion to the examined surfaces, however, does not seem to be mediated by plasma ADP.

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FIBRONECTIN IS REQUIRED FOR PLATELET ADHESION AND FOR THROMBUS FORMATION ON SUBENDOTHELIUM AND COLLAGEN SURFACES

10.1055/s-0038-1643558 ◽

1987 ◽

Author(s):

E Bastida ◽

G Escolar ◽

R Castillo ◽

A Ordinas ◽

J J Sixma

Keyword(s):

Platelet Adhesion ◽

Thrombus Formation ◽

Fibrillar Collagen ◽

Flow Conditions ◽

Shear Rates ◽

Human Collagen ◽

Platelet Thrombus ◽

Computerized System ◽

Total Coverage

Fibronectin (FN) plays a role in several adhesion mediated functions including the interaction of platelets with subendothelium.We investigated the role of plasma FN in platelet adhesion and platelet thrombus formation under flow conditions.To do this we used two different perfusion models:1)the annular chamber with α -chymotrypsin-treated rabbit vessel segments and 2)the flat chamber with coverslips coated with fibrillar purified human collagen type III.Perfusates consisted of washed platelets, and washed red blood celIs,suspended in normal or FN-depleted plasma.Perfusions were carried out for 10 min at shear rates of 300 or 1300 sec™1 Platelet deposition and thrombus dimensions were morphometrically evaluated by a computerized system. We found that depletion of plasma FN significantly reduced the percentage of total coverage surface and percentage of platelet thrombus, at both shear rates studied, and in both perfusion systems (p < 0.01)(p < 0.01).The dimensions of the platelet thrombi formed in perfusions at high shear rate were also significantly reduced in perfusions carried out with FN-depleted plasma.(p < 0.01). Addition of purified FN to FN-depleted perfusates restored all the values to those measured in the control perfusions.These results indicate that, in addition to supporting platelet adhesion to the subendothelium and to fibrillar collagen, FN contributes to platelet thrombus formation under flow conditions.

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Important Regulatory Role of Activated Platelet-Derived Procoagulant Activity in the Propagation of Thrombi Formed Under Arterial Blood Flow Conditions

Circulation Journal ◽

10.1253/circj.cj-08-0465 ◽

2009 ◽

Vol 73 (3) ◽

pp. 540-548 ◽

Cited By ~ 19

Author(s):

Noriko Tamura ◽

Isao Kitajima ◽

Yota Kawamura ◽

Eri Toda ◽

Yu Eguchi ◽

...

Keyword(s):

Blood Flow ◽

Procoagulant Activity ◽

Arterial Blood Flow ◽

Regulatory Role ◽

Flow Conditions ◽

Arterial Blood

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MATHEMATICAL MODEL FOR POROUS INFLUENCE THROUGH MILD STENOSIS THROMBOSISIS OVER DELIVERY OF OXYGEN AND NUTRIENTS ARTERIES

Advances in Mathematics: Scientific Journal ◽

10.37418/amsj.10.1.46 ◽

2021 ◽

Vol 10 (1) ◽

pp. 463-469

Author(s):

A. Kumar

Keyword(s):

Mathematical Model ◽

Surface Roughness ◽

Blood Flow ◽

Blood Vessel ◽

Arterial Blood Flow ◽

Maximum Height ◽

Flow Conditions ◽

Newtonian Flow ◽

Arterial Blood ◽

Mild Stenosis

In order to understand the irregular flow conditions of blood in a locally constricted blood vessel, analytical results are obtained for a porous effect on oscillatory blood flow that acts as a Newtonian flow. Compared to the radius of the unconstricted tube, the surface roughness is presumed to be cosine-shaped and the maximum height of the roughness is very small. The main focus of investigation of the porous effect on oscillatory arterial blood flow with mild stenosis, a mathematical model has been developed.

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HN-11500 – a Novel Thromboxane A2 Receptor Antagonist With Antithrombotic Activity in Humans at Arterial Blood Flow Conditions

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642391 ◽

1994 ◽

Vol 71 (01) ◽

pp. 103-109 ◽

Cited By ~ 26

Author(s):

Helge E Roald ◽

R Marius Barstad ◽

Anne Engen ◽

Peter Kierulf ◽

Fredrik Skjørten ◽

...

Keyword(s):

Blood Flow ◽

Receptor Antagonist ◽

Thromboxane A2 ◽

Arterial Blood Flow ◽

Fibrin Deposition ◽

Flow Conditions ◽

Thromboxane A2 Receptor ◽

Shear Rates ◽

Arterial Blood ◽

Perfusion Chamber

SummaryIn the present study we have investigated the effect of a 100 mg single oral dose of a newly developed thromboxane A2 receptor antagonist on collagen-induced thrombogenesis in flowing human non-anticoagulated blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils on a cover slip placed in a parallel-plate perfusion chamber. Shear rates at the collagen surface were characteristic for medium sized (650 s−1) and moderately stenosed (2,600 s−1) arteries. Blood-collagen interactions were morphologically quantified as platelet-collagen adhesion, fibrin deposition and thrombus volume. Activation peptides of coagulation, fibrinopeptide A (FPA), and of platelets, β-thromboglobulin (β-TG), were measured immediately distal to the perfusion chamber.HN-11500 ingestion reduced significantly the thrombus volume by 32% at 2,600 s−1, but not at 650 s−1. However, transmission electron microscopy revealed loosely packed and less degranulated platelets at 650 s−1. The β-TG plasma levels were also reduced at both shear rates by the HN-11500 ingestion. The platelet-collagen adhesion was significantly enhanced at both shear rates. This was apparently a consequence of higher platelet concentrations at the collagen surface, because fewer platelets were consumed by the thrombi after the drug ingestion. In contrast, the coagulation, as measured by fibrin deposition and FPA plasma levels, was not significantly affected by HN-11500.Thus, it appears that the thromboxane A2 receptor antagonist HN-11500 reduces the thrombotic response by primarily impairing the platelet function at arterial blood flow conditions, and particularly at high wall shear rates.

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Relationship between Endothelial Tissue Factor and Thrombogenesis under Blood Flow Conditions

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649812 ◽

1995 ◽

Vol 74 (02) ◽

pp. 778-783 ◽

Cited By ~ 24

Author(s):

Armelle Diquélou ◽

Dominique Dupouy ◽

Dominique Gaspin ◽

Jacques Constans ◽

Pierre Sié ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Flow ◽

Tissue Factor ◽

Thrombus Formation ◽

Luminal Surface ◽

Fibrin Deposition ◽

Flow Conditions ◽

The Impact ◽

The Relationship ◽

Endothelial Tissue

SummaryWe have evaluated the relationship between the level of tissue factor (TF) expression by stimulated endothelial cells and thrombus formation under blood flow conditions. Cultures of human umbilical venous endothelial cells (HUVECs) were treated in order to express different levels of TF activity. They were stimulated for 4 h with either I) lipopolysaccharides (LPS, 10 µg/ml), II) recombinant interleukin Iß (IL1ß, 50 Ul/ml) or III) simultaneously with LPS and IL1ß (LPS + IL1ß). TF activity was low on confluent HUVECs or on the corresponding extracellular-matrix (ECM prepared by exposure of HUVECs to 0.1 N NH4OH). In contrast, it was high when HUVECs were stimulated with LPS or IL1ß, and significantly higher (p <0.05) with LPS+IL1ß. The TF activity associated with the stimulated ECM was 2-fold higher (p <0.05) than that expressed on the luminal surface of the stimulated HUVECs, irrespective of the agonist or combination of agonists used.These surfaces were exposed to non-anticoagulated human blood at a venous (50 s-1) and an arterial (650 s-1) wall shear rate in parallel-plate perfusion chambers for 5 min. Thrombus formation was morphologically quantified by measuring the deposition of platelets and fibrin. Fibrin deposition was also immunologically quantified. Fibrin deposition was related to the level of TF expression. Non-stimulated HUVECs and corresponding ECMs were not thrombogenic. The luminal surface of HUVECs stimulated with LPS or IL1ß alone expressed low levels of TF activity and was a poor inducer of platelet deposition and fibrin deposition (<15%) at 50 s-1. In contrast, fibrin deposition increased to 80% when the cells were stimulated with LPS and IL1ß simultaneously. This fibrin deposition was comparable to that found on the corresponding ECM, despite a two-fold lower TF activity. However, at 650 s-1, platelet and fibrin deposition on HUVECs stimulated with LPS + IL1ß were significantly lower than that observed on the corresponding ECM. In all circumstances, the thrombogenicity was TF-dependent, since fibrin deposition was totally blocked by anti-TF antibodies. Thus, it appears that the level of TF activity expressed on endothelial cells governs thrombus formation. However, the impact of TF expression on thrombus formation is also affected by the blood flow.

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