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Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan

BACKGROUND: Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit p...

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Autores principales: Yamakawa, Kazuma, Umemura, Yutaka, Hayakawa, Mineji, Kudo, Daisuke, Sanui, Masamitsu, Takahashi, Hiroki, Yoshikawa, Yoshiaki, Hamasaki, Toshimitsu, Fujimi, Satoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966726/
https://www.ncbi.nlm.nih.gov/pubmed/27472991
http://dx.doi.org/10.1186/s13054-016-1415-1
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author Yamakawa, Kazuma
Umemura, Yutaka
Hayakawa, Mineji
Kudo, Daisuke
Sanui, Masamitsu
Takahashi, Hiroki
Yoshikawa, Yoshiaki
Hamasaki, Toshimitsu
Fujimi, Satoshi
author_facet Yamakawa, Kazuma
Umemura, Yutaka
Hayakawa, Mineji
Kudo, Daisuke
Sanui, Masamitsu
Takahashi, Hiroki
Yoshikawa, Yoshiaki
Hamasaki, Toshimitsu
Fujimi, Satoshi
author_sort Yamakawa, Kazuma
collection PubMed
description BACKGROUND: Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis. METHODS: This post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores. RESULTS: Participants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13–17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets. CONCLUSIONS: The analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543). Registered on 10 December 2013. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1415-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-49667262016-07-30 Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan Yamakawa, Kazuma Umemura, Yutaka Hayakawa, Mineji Kudo, Daisuke Sanui, Masamitsu Takahashi, Hiroki Yoshikawa, Yoshiaki Hamasaki, Toshimitsu Fujimi, Satoshi Crit Care Research BACKGROUND: Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis. METHODS: This post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores. RESULTS: Participants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13–17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets. CONCLUSIONS: The analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543). Registered on 10 December 2013. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1415-1) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-29 2016 /pmc/articles/PMC4966726/ /pubmed/27472991 http://dx.doi.org/10.1186/s13054-016-1415-1 Text en © The Author(s). 2016 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 Research
Yamakawa, Kazuma
Umemura, Yutaka
Hayakawa, Mineji
Kudo, Daisuke
Sanui, Masamitsu
Takahashi, Hiroki
Yoshikawa, Yoshiaki
Hamasaki, Toshimitsu
Fujimi, Satoshi
Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan
title Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan
title_full Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan
title_fullStr Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan
title_full_unstemmed Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan
title_short Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan
title_sort benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in japan
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966726/
https://www.ncbi.nlm.nih.gov/pubmed/27472991
http://dx.doi.org/10.1186/s13054-016-1415-1
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