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      Pathophysiologic and Therapeutic Perspectives Based on Thrombus Histology in Stroke

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          Abstract

          Recent advances in endovascular thrombectomy have enabled the histopathologic analysis of fresh thrombi in patients with acute stroke. Histologic analysis has shown that the thrombus composition is very heterogeneous between patients. However, the distribution pattern of each thrombus component often differs between patients with cardiac thrombi and those with arterial thrombi, and the efficacy of endovascular thrombectomy is different according to the thrombus composition. Furthermore, the thrombus age is related to the efficacy of reperfusion therapy. Recent studies have shown that neutrophils and neutrophil extracellular traps contribute to thrombus formation and resistance to reperfusion therapy. Histologic features of thrombi in patients with stroke may provide some clues to stroke etiology, which is helpful for determining the strategy of stroke prevention. Research on thrombus may also be helpful for improving reperfusion therapy, including the development of new thrombolytic agents.

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          Most cited references62

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          Thrombosis: tangled up in NETs.

          The contributions by blood cells to pathological venous thrombosis were only recently appreciated. Both platelets and neutrophils are now recognized as crucial for thrombus initiation and progression. Here we review the most recent findings regarding the role of neutrophil extracellular traps (NETs) in thrombosis. We describe the biological process of NET formation (NETosis) and how the extracellular release of DNA and protein components of NETs, such as histones and serine proteases, contributes to coagulation and platelet aggregation. Animal models have unveiled conditions in which NETs form and their relation to thrombogenesis. Genetically engineered mice enable further elucidation of the pathways contributing to NETosis at the molecular level. Peptidylarginine deiminase 4, an enzyme that mediates chromatin decondensation, was identified to regulate both NETosis and pathological thrombosis. A growing body of evidence reveals that NETs also form in human thrombosis and that NET biomarkers in plasma reflect disease activity. The cell biology of NETosis is still being actively characterized and may provide novel insights for the design of specific inhibitory therapeutics. After a review of the relevant literature, we propose new ways to approach thrombolysis and suggest potential prophylactic and therapeutic agents for thrombosis.
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            Neutrophil extracellular traps in ischemic stroke thrombi.

            Neutrophil extracellular traps (NETs) have been shown to promote thrombus formation. Little is known about the exact composition of thrombi that cause ischemic stroke. In particular, no information is yet available on the presence of NETs in cerebral occlusions. Such information is, however, essential to improve current thrombolytic therapy with tissue plasminogen activator (t-PA). This study aimed at investigating the presence of neutrophils and more specifically NETs in ischemic stroke thrombi.
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              Risk of Arterial Thromboembolism in Patients With Cancer

              The risk of arterial thromboembolism in patients with cancer is incompletely understood.
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                Author and article information

                Journal
                J Stroke
                J Stroke
                JOS
                Journal of Stroke
                Korean Stroke Society
                2287-6391
                2287-6405
                January 2020
                31 January 2020
                : 22
                : 1
                : 64-75
                Affiliations
                [a ]Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
                [b ]Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, Seoul, Korea
                [c ]Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
                Author notes
                Correspondence: Ji Hoe Heo Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2228-1605 Fax: +82-2-393-0705 E-mail: jhheo@ 123456yuhs.ac
                Article
                jos-2019-03440
                10.5853/jos.2019.03440
                7005358
                32027792
                32bb178e-3cd1-4491-9204-6b7336782ad8
                Copyright © 2020 Korean Stroke Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 December 2019
                : 22 January 2020
                : 23 January 2020
                Categories
                Review

                intracranial thrombus,histology,stroke,thrombectomy
                intracranial thrombus, histology, stroke, thrombectomy

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