The overview of  brinolysis system contemporary concepts and of its disorders diagnostic methods

Zhalyalov, A.S.; Баландина, А. Н.; Kuprash, A.D.; Srivastava, Anshu; Shibeko, Alexey M.

doi:10.24287/1726-1708-2017-16-1-69-82

Cited by 8 publications

(34 citation statements)

References 62 publications

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“…The main enzyme that breaks down fibrin is plasmin, which is formed from inactive plasminogen during activation. The process of plasminogen activation includes 3 pathways: -internal; -external; -exogenous [6]. The external path is the main one, however, both the internal and exogenous paths play an important role.…”

Section: Fibrinolytic Systemmentioning

confidence: 99%

“…Additionally, the fibrin filaments are strengthened by crosslinking due to factor XIIIa (in addition, factor XIIIa attaches a2-antiplasmin molecules to the fibrin filaments, which impairs the lysis process). The parameters of the fibrin network (fibril thickness and average length between branches) depend on the polymerization conditions -pH of the medium, salt concentration, ionic strength, thrombin concentration [6,12].…”

Section: Fibrinogen and Fibrinmentioning

confidence: 99%

“…Immunological methods for measuring D-dimer show high sensitivity against thrombosis (93-96%), but low specificity (43-53%). D-dimer test readings are E3S Web of Conferences 215, 05002 (2020) BFT-2020 https://doi.org/10.1051/e3sconf/202021505002 recommended for use in scoring calculations of the probability of deep vein thrombosis of the lower extremities and pulmonary embolism [6].…”

Section: D-dimermentioning

confidence: 99%

“…The main organ that synthesizes plasminogen is the liver, but this protein is present in the extravascular space of many other tissues. It is known that in addition to the liver, it can be synthesized by the kidneys and the cornea [6].…”

Section: Plasminogen and Plasminmentioning

confidence: 99%

“…Even in the case of homozygous plasminogen deficiency, thrombotic pathologies are not observed in such patients. The absence of thrombotic pathologies in such patients is probably due to the fact that even low concentrations of plasminogen (from 4 to 51%) are sufficient for the normal functioning of the fibrinolysis system [6].…”

Section: Plasminogen and Plasminmentioning

confidence: 99%

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Modern concepts of the fibrinolytic system

2020

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Among all medical pathologies, cardiovascular diseases are the most dangerous and deadly. On the one hand, thrombosis is a natural reaction of a person to damage to blood vessels, on the other hand, thrombosis is often the cause of death in the event of cardiovascular disease. There is a natural process called fibrinolysis to dissolve a blood clot after the bleeding has stopped and preventing vascular occlusion. This article examines current understanding of the human fibrinolytic system, main elements of fibrinolytic system and also addresses the topic of thrombolytic therapy.

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Section: Fibrinolytic Systemmentioning

confidence: 99%

Section: Fibrinogen and Fibrinmentioning

confidence: 99%

Section: D-dimermentioning

confidence: 99%

Section: Plasminogen and Plasminmentioning

confidence: 99%

Section: Plasminogen and Plasminmentioning

confidence: 99%

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Modern concepts of the fibrinolytic system

2020

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Redistribution of TPA Fluxes in the Presence of PAI-1 Regulates Spatial Thrombolysis

Shibeko

Chopard

Hoekstra

et al. 2020

Biophysical Journal

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The fibrin clot is gelatinous matter formed upon injury to stop blood loss and is later destroyed by fibrinolysis, an enzymatic cascade with feedback. Pharmacological fibrinolysis stimulation is also used to destroy pathological, life-threatening clots and thrombi (thrombolysis). The regulation of the nonlinear spatially nonuniform fibrinolytic process in thrombolysis is not currently well understood. We developed a reaction-diffusion-advection model of thrombolysis by tissue plasminogen activator (TPA) in an occluded vessel with a pressure gradient. Sensitivity-analysis-based model reduction was used to reveal the critical processes controlling different steps of thrombolysis. The propagation of thrombolysis in the system without flow was predominantly controlled by TPA diffusion, whereas transport of other active components was rendered nonessential either by their high fibrin-binding parameters and short lifetimes or their initial uniform distribution. The concentration of the main TPA inhibitor plasminogen activator inhibitor 1 (PAI-1) controlled both the extent of lysis propagation and the shape of fibrin spatial distribution during lysis. Interestingly, PAI-1 remained important even when its concentration was an order of magnitude below that of TPA because of its role at the edge of the diffusing TPA front. The system was robust to reaction rate constant perturbations. Using these data, a reduced model of thrombolysis was proposed. In the presence of flow, convection of TPA was the critical controlling process; although the role of PAI-1 concentration was much less in the presence of flow, its influence became greater in the presence of collateral bypassing vessels, which sufficiently reduced TPA flux through the thrombus. Flow bypass through the collateral vessel caused a decrease in TPA flux in the clotted vessel, which increased the PAI-1/TPA ratio, thus making PAI-1-induced inhibition relevant for the regulation of spatial lysis up to its arrest.

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