Identifying Sepsis Populations Benefitting from Anticoagulant Therapy: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model

behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis Trauma (FORECAST) Study Group

Research output: Contribution to journalArticle

Abstract

Background Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. Objective This article identifies the optimal target of anticoagulant therapy in sepsis. Methods We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. Results The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. Conclusion Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.

Original languageEnglish
Pages (from-to)1740-1751
Number of pages12
JournalThrombosis and Haemostasis
Volume119
Issue number11
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Disseminated Intravascular Coagulation
Anticoagulants
Sepsis
Cohort Studies
Prospective Studies
Population
APACHE
Hemostasis
Thrombosis
Therapeutics
Organ Dysfunction Scores
Hospital Mortality
Intensive Care Units
Japan
Regression Analysis
Medicine
Control Groups

Keywords

  • anticoagulants
  • critically ill
  • disseminated intravascular coagulation
  • sepsis
  • septic shock

ASJC Scopus subject areas

  • Hematology

Cite this

behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis Trauma (FORECAST) Study Group (2019). Identifying Sepsis Populations Benefitting from Anticoagulant Therapy: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model. Thrombosis and Haemostasis, 119(11), 1740-1751. https://doi.org/10.1055/s-0039-1693740

Identifying Sepsis Populations Benefitting from Anticoagulant Therapy : A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model. / behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis Trauma (FORECAST) Study Group.

In: Thrombosis and Haemostasis, Vol. 119, No. 11, 01.01.2019, p. 1740-1751.

Research output: Contribution to journalArticle

behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis Trauma (FORECAST) Study Group 2019, 'Identifying Sepsis Populations Benefitting from Anticoagulant Therapy: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model', Thrombosis and Haemostasis, vol. 119, no. 11, pp. 1740-1751. https://doi.org/10.1055/s-0039-1693740
behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis Trauma (FORECAST) Study Group. Identifying Sepsis Populations Benefitting from Anticoagulant Therapy: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model. Thrombosis and Haemostasis. 2019 Jan 1;119(11):1740-1751. https://doi.org/10.1055/s-0039-1693740
behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis Trauma (FORECAST) Study Group. / Identifying Sepsis Populations Benefitting from Anticoagulant Therapy : A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model. In: Thrombosis and Haemostasis. 2019 ; Vol. 119, No. 11. pp. 1740-1751.
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abstract = "Background Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. Objective This article identifies the optimal target of anticoagulant therapy in sepsis. Methods We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. Results The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. Conclusion Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.",
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T1 - Identifying Sepsis Populations Benefitting from Anticoagulant Therapy

T2 - A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model

AU - behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis Trauma (FORECAST) Study Group

AU - Yamakawa, Kazuma

AU - Gando, Satoshi

AU - Ogura, Hiroshi

AU - Umemura, Yutaka

AU - Kabata, Daijiro

AU - Shintani, Ayumi

AU - Shiraishi, Atsushi

AU - Saitoh, Daizoh

AU - Fujishima, Seitato

AU - Mayumi, Toshihiko

AU - Kushimoto, Shigeki

AU - Abe, Toshikazu

AU - Shiino, Yasukazu

AU - Nakada, Taka Aki

AU - Tarui, Takehiko

AU - Hifumi, Toru

AU - Otomo, Yasuhiro

AU - Okamoto, Kohji

AU - Kotani, Joji

AU - Sakamoto, Yuichiro

AU - Sasaki, Junichi

AU - Shiraishi, Shin Ichiro

AU - Takuma, Kiyotsugu

AU - Tsuruta, Ryosuke

AU - Hagiwara, Akiyoshi

AU - Masuno, Tomohiko

AU - Takeyama, Naoshi

AU - Yamashita, Norio

AU - Ikeda, Hiroto

AU - Ueyama, Masashi

AU - Fujimi, Satoshi

AU - Mizushima, Yasuaki

AU - Tasaki, Osamu

AU - Mizobata, Yasumitsu

AU - Funakoshi, Hiraku

AU - Okuyama, Toshiro

AU - Yamashita, Iwao

AU - Kanai, Toshio

AU - Yamada, Yasuo

AU - Aibiki, Mayuki

AU - Sato, Keiji

AU - Yamashita, Susumu

AU - Yoshida, Kenichi

AU - Kasaoka, Shunji

AU - Kon, Akihide

AU - Rinka, Hiroshi

AU - Kato, Hiroshi

AU - Okudera, Hiroshi

AU - Narimatsu, Eichi

AU - Fujiwara, Toshifumi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. Objective This article identifies the optimal target of anticoagulant therapy in sepsis. Methods We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. Results The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. Conclusion Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.

AB - Background Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. Objective This article identifies the optimal target of anticoagulant therapy in sepsis. Methods We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. Results The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. Conclusion Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.

KW - anticoagulants

KW - critically ill

KW - disseminated intravascular coagulation

KW - sepsis

KW - septic shock

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