Antithrombin and mortality in severe pneumonia patients with sepsis‐associated disseminated intravascular coagulation: an observational nationwide study

Tagami, Takashi; Matsui, Hiroki; Horiguchi, Hiromasa; Fushimi, Kiyohide; Yasunaga, Hideo

doi:10.1111/jth.12643

Cited by 137 publications

(168 citation statements)

References 63 publications

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“…Recently, two studies that used a nationwide administrative database reported that AT supplementation was beneficial in treating sepsis‐induced DIC 37, 38. However, the evidence for this practice is insufficient.…”

Section: Antithrombinmentioning

confidence: 99%

A summary of the Japan septic disseminated intravascular coagulation study

Hayakawa

Ono

2018

Acute Medicine & Surgery

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Over the past few decades, the large, international, randomized controlled trials of anticoagulant therapies for patients with sepsis have not yielded any improvement in mortality rates. However, in Japan, anticoagulant therapies are administered for sepsis patients with disseminated intravascular coagulation (DIC), but not for sepsis patients without DIC. Furthermore, epidemiological data regarding sepsis in Japan are scarce. Therefore, a nationwide multicenter retrospective observational study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study, was undertaken. The JSEPTIC DIC study enrolled 42 intensive care units and included 3,195 patients with sepsis. The results of the JSEPTIC DIC study indicated the following: (i) anticoagulant therapy may be effective in sepsis‐induced DIC patients at high risk for death, (ii) recombinant human soluble thrombomodulin administration and antithrombin supplementation are associated with survival benefits in patients with sepsis‐induced DIC.

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Section: Antithrombinmentioning

confidence: 99%

A summary of the Japan septic disseminated intravascular coagulation study

Hayakawa

Ono

2018

Acute Medicine & Surgery

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“…There were no severe adverse events in either group. These findings suggests that plasma derived APC as a remarkably reduced dose compared to rhAPC can improve DIC, without increasing bleeding and its effects should be evaluated in future [27] (Kybersept) Gando et al [29] 2013 Tagami et al [30] 2014 Sepsis-associated DIC in severe pneumonia [33] (Prowess trial) Vincent et al [35] (Enhance trial) [36] (Address trial) Ranieri et al [37] (Prowess shock) Rimmer et al [38] 2012 [47] (HETRASE study) Abraham et al [50] (OPTIMIST trial) [52] (CAPTIVATE trial) Allen KS et al . Anticoagulant modulation of inflammation in severe sepsis trials.…”

Section: Protein Cmentioning

confidence: 99%

“…The patients were randomly assigned to receive supplemental doses of AT or placebo for 3 d. They noted that AT treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with a control group without an increased incidence of bleeding complications. Tagami et al [30] identified 9075 patients with severe pneumonia and sepsis related DIC in a nationwide Japanese database [30] . Using propensity matching to account for confounding factors, they identified 2194 pairs of matched patients who did or did not receive AT treatment.…”

Section: Antithrombinmentioning

confidence: 99%

Anticoagulant modulation of inflammation in severe sepsis

Allen

Sawheny

Kinasewitz

2015

WJCCM

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Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis.

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“…Two studies by Tagami et al (14,15) analyzed the effects of AT supplementation using a nationwide administrative database and reported that AT treatment was beneficial in treating sepsis-induced DIC patients. A major limitation of these studies was that the database did not contain laboratory data or information regarding the clinical severity of the patients' conditions (14,15). Furthermore, the etiologies of sepsis were solely restricted to pneumonia (14) and perforation of the lower intestinal tract (15).…”

Section: Introductionmentioning

confidence: 99%

“…A major limitation of these studies was that the database did not contain laboratory data or information regarding the clinical severity of the patients' conditions (14,15). Furthermore, the etiologies of sepsis were solely restricted to pneumonia (14) and perforation of the lower intestinal tract (15). Gando et al (16) performed a randomized trial of AT supplementation in sepsis-induced DIC patients with low risk of death.…”

Section: Introductionmentioning

confidence: 99%

Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation

Hayakawa¹,

Kudo²,

Saito

et al. 2016

Shock

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ABSTRACT-Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of ATsupplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n ¼ 715, AT group; n ¼ 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n ¼ 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P ¼ 0.034). However, quintile-stratified propensity score analysis (n ¼ 1,784, odds ratio: 0.823 [0.646-1.050], P ¼ 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P ¼ 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P ¼ 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

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Antithrombin and mortality in severe pneumonia patients with sepsis‐associated disseminated intravascular coagulation: an observational nationwide study

Cited by 137 publications

References 63 publications

A summary of the Japan septic disseminated intravascular coagulation study

A summary of the Japan septic disseminated intravascular coagulation study

Anticoagulant modulation of inflammation in severe sepsis

Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation

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