Stasis Thrombi Induced by Bacterial Endotoxin

Thomas, Duncan P.; Wessler, Stanford

doi:10.1161/01.res.14.6.486

Cited by 32 publications

(7 citation statements)

References 20 publications

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“…One of the earliest of these was from Wessler (reviewed in (21)) and involved double ligation of a rabbit's jugular vein to promote stasis immediately after the blood's coagulability had been altered, e.g., by injection of a prothrombotic stimulant such as serum (22) or bacterial endotoxin (23). Later animal models, some known as the ''St.…”

Section: Introductionmentioning

confidence: 99%

A Mathematical Model of Venous Thrombosis Initiation

Elizondo

Fogelson

2016

Biophysical Journal

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We present a mathematical model for the initiation of venous thrombosis (VT) due to slow flow and the consequent activation of the endothelial cells (ECs) lining the vein, in the absence of overt mechanical disruption of the EC layer. It includes all reactions of the tissue factor (TF) pathway of coagulation through fibrin formation, incorporates the accumulation of blood cells on activated ECs, accounts for the flow-mediated delivery and removal of coagulation proteins and blood cells from the locus of the reactions, and accounts for the activity of major inhibitors including heparan-sulfate-accelerated antithrombin and activated protein C. The model reveals that the occurrence of robust thrombin generation (a thrombin burst) depends in a threshold manner on the density of TF on the activated ECs and on the concentration of thrombomodulin and the degree of heparan-sulfate accelerated antithrombin activity on those cells. Small changes in any of these in appropriate narrow ranges switches the response between ''no burst'' and ''burst.'' The model predicts synergies among the inhibitors, both in terms of each inhibitor's multiple targets, and in terms of interactions between the different inhibitors. The model strongly suggests that the rate and extent of accumulation of activated monocytes, platelets, and MPs that can support the coagulation reactions has a powerful influence on whether a thrombin burst occurs and the thrombin response when it does. The slow rate of accumulation of cells supporting coagulation is one reason that the progress of VT is so much slower than that of arterial thrombosis initiated by subendothelial exposure.

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Section: Introductionmentioning

confidence: 99%

A Mathematical Model of Venous Thrombosis Initiation

Elizondo

Fogelson

2016

Biophysical Journal

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“…Stasis may be seen as a permissive factor allowing local thrombin generation while excluding the normal defence mechanisms of the liver and microcirculation in removing circulating activated clotting factors. Trace amounts of activated procoagulants and bacterial endotoxin have been shown experimentally to produce a transient hypercoagulable state which, in the presence of local stasis is a potent stimulus for thrombus formation (22,23). Since the concentrations of immunoreactive IL-1~ in the plasma of patients with rheumatoid arthritis are of the order of 100 pg/ml and even in the synovial fluid of such patients does not usually exceed 2 ng/ml (24,25), the doses injected in the present study (1 j.tg/kg) may be considered relatively high, but were nevertheless an insufficient thrombogenic stimulus even in the presence of local stasis.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Interleukin-1 on Venous Endothelium – An Ultrastructural Study

et al. 1991

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SummaryThe effect of systemic interleukin-1 (IL-1) on venous endothelium in the presence and absence of stasis has been studied by scanning electron microscopy (SEM). Recombinant human IL-1β at a concentration of 1 εg/kg or saline was injected intravenously into rabbits and allowed to circulate for 0.5 or 4.0 h after which complete stasis was induced for 1 h in an isolated segment of each jugular vein. One vein segment was then excised and the contents examined macroscopically for thrombi, while the other segment was fixed for SEM examination. When examined by SEM the endothelium from rabbits injected with IL-1β was perturbed with increased surface microvilli, blebs and gaps at cell junctions when compared with saline controls. Fibrin deposition was also observed after IL-1β, as was the adherence of essentially non-activated platelets to intact endothelium. However, macroscopic thrombi were not formed in isolated vein segments. We conclude that although fibrin strands and platelets were deposited on the endothelium, IL-1 is not a sufficiently powerful procoagulant stimulus to lead to an occlusive thrombus in acute experiments.

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“…Their findings were in keeping with the hypothesis that, because of biochemical amplification during coagulation, the fur ther removed an activated clotting factor is from fibrin formation the fewer are the number of mole cules of that protease required to produce thrombo sis. Activation of clotting, whether it be by serum, 44 endotoxin, 45 a surface active agent, 46 or a highly pu rified clotting factor 43 when combined with local sta sis, leads rapidly to clotting of noncirculating blood.…”

Section: Role Of Activated Clotting Factorsmentioning

confidence: 99%

Overview of Venous Thrombogenesis

Thomas

1988

Semin Thromb Hemost

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In the pathogenesis of venous thrombosis, stasis is essentially a permissive factor, allowing the normal defense mechanisms of the body to be circumvented. Although a platelet monolayer is an insufficient stimulus for fibrin formation, even in the presence of stasis, trace amounts of an activated clotting factor are highly thrombogenic in an area of retarded blood flow. The available clinical and experimental data suggest that, if thrombin generation is reduced, the great majority of venous thrombi are prevented.

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Stasis Thrombi Induced by Bacterial Endotoxin

Cited by 32 publications

References 20 publications

A Mathematical Model of Venous Thrombosis Initiation

A Mathematical Model of Venous Thrombosis Initiation

The Effect of Interleukin-1 on Venous Endothelium – An Ultrastructural Study

Overview of Venous Thrombogenesis

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