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Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential
Thrombomodulin plays a vital role in maintaining intravascular patency due to its anticoagulant, antiinflammatory, and cytoprotective properties. However, under pathological conditions such as sepsis and systemic inflammation, endothelial thrombomodulin expression is downregulated and its function i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694689/ https://www.ncbi.nlm.nih.gov/pubmed/31416465 http://dx.doi.org/10.1186/s13054-019-2552-0 |
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author | Ito, Takashi Thachil, Jecko Asakura, Hidesaku Levy, Jerrold H. Iba, Toshiaki |
author_facet | Ito, Takashi Thachil, Jecko Asakura, Hidesaku Levy, Jerrold H. Iba, Toshiaki |
author_sort | Ito, Takashi |
collection | PubMed |
description | Thrombomodulin plays a vital role in maintaining intravascular patency due to its anticoagulant, antiinflammatory, and cytoprotective properties. However, under pathological conditions such as sepsis and systemic inflammation, endothelial thrombomodulin expression is downregulated and its function impaired. As a result, administering thrombomodulin represents a potential therapeutic modality. Recently, the effect of recombinant thrombomodulin administration in sepsis-induced coagulopathy was evaluated in a randomized controlled study (SCARLET). A 2.6% 28-day absolute mortality reduction (26.8% vs. 29.4%) was reported in 800 patients studied that was not statistically significant; however, a post hoc analysis revealed a 5.4% absolute mortality reduction among the patients who fulfilled the entry criterion at baseline. The risk of bleeding did not increase compared to placebo control. Favorable effects of thrombomodulin administration have been reported not only in sepsis-induced coagulopathy but also in disseminated intravascular coagulations with various backgrounds. Interestingly, beneficial effects of recombinant thrombomodulin in respiratory, renal, and cardiovascular diseases might depend on its anti-inflammatory mechanisms. In this review, we summarize the accumulated knowledge of endogenous as well as recombinant thrombomodulin from basic to clinical aspects and suggest future directions for this novel therapeutic agent. |
format | Online Article Text |
id | pubmed-6694689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66946892019-08-19 Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential Ito, Takashi Thachil, Jecko Asakura, Hidesaku Levy, Jerrold H. Iba, Toshiaki Crit Care Review Thrombomodulin plays a vital role in maintaining intravascular patency due to its anticoagulant, antiinflammatory, and cytoprotective properties. However, under pathological conditions such as sepsis and systemic inflammation, endothelial thrombomodulin expression is downregulated and its function impaired. As a result, administering thrombomodulin represents a potential therapeutic modality. Recently, the effect of recombinant thrombomodulin administration in sepsis-induced coagulopathy was evaluated in a randomized controlled study (SCARLET). A 2.6% 28-day absolute mortality reduction (26.8% vs. 29.4%) was reported in 800 patients studied that was not statistically significant; however, a post hoc analysis revealed a 5.4% absolute mortality reduction among the patients who fulfilled the entry criterion at baseline. The risk of bleeding did not increase compared to placebo control. Favorable effects of thrombomodulin administration have been reported not only in sepsis-induced coagulopathy but also in disseminated intravascular coagulations with various backgrounds. Interestingly, beneficial effects of recombinant thrombomodulin in respiratory, renal, and cardiovascular diseases might depend on its anti-inflammatory mechanisms. In this review, we summarize the accumulated knowledge of endogenous as well as recombinant thrombomodulin from basic to clinical aspects and suggest future directions for this novel therapeutic agent. BioMed Central 2019-08-15 /pmc/articles/PMC6694689/ /pubmed/31416465 http://dx.doi.org/10.1186/s13054-019-2552-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Ito, Takashi Thachil, Jecko Asakura, Hidesaku Levy, Jerrold H. Iba, Toshiaki Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential |
title | Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential |
title_full | Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential |
title_fullStr | Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential |
title_full_unstemmed | Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential |
title_short | Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential |
title_sort | thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694689/ https://www.ncbi.nlm.nih.gov/pubmed/31416465 http://dx.doi.org/10.1186/s13054-019-2552-0 |
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