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

dc.contributor.author

Ito, Takashi

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Thachil, Jecko

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Asakura, Hidesaku

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Levy, Jerrold H

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Iba, Toshiaki

dc.date.accessioned

2019-09-01T15:54:48Z

dc.date.available

2019-09-01T15:54:48Z

dc.date.issued

2019-08-15

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2019-09-01T15:54:47Z

dc.description.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.

dc.identifier

10.1186/s13054-019-2552-0

dc.identifier.issn

1364-8535

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1466-609X

dc.identifier.uri

https://hdl.handle.net/10161/19264

dc.language

eng

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Springer Science and Business Media LLC

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Critical care (London, England)

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10.1186/s13054-019-2552-0

dc.subject

Bleeding

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Coagulopathy

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Disseminated intravascular coagulation (DIC)

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Randomized controlled trial

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Recombinant thrombomodulin

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Sepsis

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Septic shock

dc.title

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

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Journal article

pubs.begin-page

280

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1

pubs.organisational-group

School of Medicine

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Duke

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Surgery, Cardiovascular and Thoracic Surgery

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Surgery

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Clinical Science Departments

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Anesthesiology, Cardiothoracic

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Anesthesiology

pubs.publication-status

Published

pubs.volume

23

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