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      Factors Affecting the Formation and Treatment of Thrombosis by Natural and Synthetic Compounds

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          Abstract

          Venous thromboembolism (VTE) refers to deep vein thrombosis (DVT), whose consequence may be a pulmonary embolism (PE). Thrombosis is associated with significant morbidity and mortality and is the third most common cardiovascular disease after myocardial infarction and stroke. DVT is associated with the formation of a blood clot in a deep vein in the body. Thrombosis promotes slowed blood flow, hypoxia, cell activation, and the associated release of many active substances involved in blood clot formation. All thrombi which adhere to endothelium consist of fibrin, platelets, and trapped red and white blood cells. In this review, we summarise the impact of various factors affecting haemostatic disorders leading to blood clot formation. The paper discusses the causes of thrombosis, the mechanism of blood clot formation, and factors such as hypoxia, the involvement of endothelial cells (ECs), and the activation of platelets and neutrophils along with the effects of bacteria and reactive oxygen species (ROS). Mechanisms related to the action of anticoagulants affecting coagulation factors including antiplatelet drugs have also been discussed. However, many aspects related to the pathogenesis of thrombosis still need to be clarified. A review of the drugs used to treat and prevent thrombosis and natural anticoagulants that occur in the plant world and are traditionally used in Far Eastern medicine has also been carried out.

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          Most cited references308

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          Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report.

          We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.
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            Extracellular DNA traps promote thrombosis.

            Neutrophil extracellular traps (NETs) are part of the innate immune response to infections. NETs are a meshwork of DNA fibers comprising histones and antimicrobial proteins. Microbes are immobilized in NETs and encounter a locally high and lethal concentration of effector proteins. Recent studies show that NETs are formed inside the vasculature in infections and noninfectious diseases. Here we report that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation. NETs perfused with blood caused platelet adhesion, activation, and aggregation. DNase or the anticoagulant heparin dismantled the NET scaffold and prevented thrombus formation. Stimulation of platelets with purified histones was sufficient for aggregation. NETs recruited red blood cells, promoted fibrin deposition, and induced a red thrombus, such as that found in veins. Markers of extracellular DNA traps were detected in a thrombus and plasma of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced thrombosis. Our observations indicate that NETs are a previously unrecognized link between inflammation and thrombosis and may further explain the epidemiological association of infection with thrombosis.
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              Mitochondrial formation of reactive oxygen species.

              The reduction of oxygen to water proceeds via one electron at a time. In the mitochondrial respiratory chain, Complex IV (cytochrome oxidase) retains all partially reduced intermediates until full reduction is achieved. Other redox centres in the electron transport chain, however, may leak electrons to oxygen, partially reducing this molecule to superoxide anion (O2-*). Even though O2-* is not a strong oxidant, it is a precursor of most other reactive oxygen species, and it also becomes involved in the propagation of oxidative chain reactions. Despite the presence of various antioxidant defences, the mitochondrion appears to be the main intracellular source of these oxidants. This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments. We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 October 2020
                November 2020
                : 21
                : 21
                : 7975
                Affiliations
                [1 ]Department of Pharmaceutical Microbiology and Microbiological Diagnostic, Faculty of Pharmacy, Medical University of Lodz, 90-235 Lodz, Poland; anna.lichota@ 123456umed.lodz.pl (A.L.); eligia.szewczyk@ 123456umed.lodz.pl (E.M.S.)
                [2 ]Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
                Author notes
                [* ]Correspondence: krzysztof.gwozdzinski@ 123456biol.uni.lodz.pl ; Tel.: +48-426-354-452
                Author information
                https://orcid.org/0000-0002-5399-3144
                https://orcid.org/0000-0001-7148-4063
                https://orcid.org/0000-0003-2590-7496
                Article
                ijms-21-07975
                10.3390/ijms21217975
                7663413
                33121005
                ef087b44-6cc6-485c-acfb-799e42bdc1a9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 September 2020
                : 23 October 2020
                Categories
                Review

                Molecular biology
                thrombosis,hypoxia,oxidative stress,saponins,flavonoids,anticoagulants
                Molecular biology
                thrombosis, hypoxia, oxidative stress, saponins, flavonoids, anticoagulants

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