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Critical Care
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Septicemia | Review

Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential

Authors: Takashi Ito, Jecko Thachil, Hidesaku Asakura, Jerrold H. Levy, Toshiaki Iba

Published in: Critical Care | Issue 1/2019

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Abstract

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.
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Metadata
Title
Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential
Authors
Takashi Ito
Jecko Thachil
Hidesaku Asakura
Jerrold H. Levy
Toshiaki Iba
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2552-0

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