Double-blind, Placebo-controlled Trial of Antithrombin III Concentrates in Septic Shock With Disseminated Intravascular Coagulation

Fourrier, F.; Chopin, C.; Huart, J. J.; Runge, Isabelle; Caron, Claudine; Goudemand, Jenny

doi:10.1378/chest.104.3.882

Cited by 373 publications

(197 citation statements)

References 20 publications

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“…In these studies, significant improvement of coagulation and fibrinolytic markers following antithrombin administration was noticed; however, antithrombin had no effect on the course of platelet counts over time [4,12,19]. In the present study, we observed a significant increase in the platelet counts and fibrinogen levels in responders.…”

Section: Discussionsupporting

confidence: 42%

“…Several studies reported an effect of antithrombin administration on hemostatic variables in critically ill patients [4,12,29]. In these studies, significant improvement of coagulation and fibrinolytic markers following antithrombin administration was noticed; however, antithrombin had no effect on the course of platelet counts over time [4,12,19].…”

Section: Discussionmentioning

confidence: 99%

“…Antithrombin III (antithrombin) works as an important, endogenous regulator of coagulation and immune response by virtue of its antithrombotic and antiinflammatory properties, and the initial decrease of antithrombin is considered to be a predictor of a poor outcome in these patients [1][2][3]. In experimental models and in patients with sepsis, severe sepsis, and septic shock, antithrombin limited or prevented development of MODS and reduced the mortality rate [4][5][6][7][8]. Contrary to these promising results, the KyberSept multicenter randomized controlled trial using highdose antithrombin over 4 days failed to demonstrate an improved outcome evaluated by 28-day-all-cause mortality in patients with severe sepsis [9].…”

Section: Introductionmentioning

confidence: 99%

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First day dynamic changes in antithrombin III activity after supplementation have a predictive value in critically ill patients

et al. 2006

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To evaluate the changes in the antithrombin III (antithrombin) values after initial supplementation to predict outcome in critically ill patients, we conducted a retrospective study. All consecutive patients admitted to the intensive care unit (ICU) and treated with antithrombin were enrolled in the study. Initial doses of 1,500 IU or 30 IU/kg antithrombin concentrates were administered over an hour. The clinical backgrounds of the patients were collected from computer-based records. Serial data of antithrombin were collected from the first day of administration (Day 0) to days 1-4. The patients were subdivided into two groups based on whether they demonstrated an increased antithrombin activity of more than 60% on the first day after the initial supplementation (responders) or not (nonresponders). Four hundred thirty-five patients were enrolled in the present study. Two hundred eighty-eight patients could achieve an antithrombin activity of more than 60%. The outcome was significantly different between the two groups. A logistic regression analysis revealed the day 1 antithrombin level and an initial increase of less than 60% after supplementation to be independently associated with ICU mortality. We also found a significant increase in the platelet counts and fibrinogen levels, and a decrease in the disseminated intravascular coagulation (DIC) scores for the responders. In conclusion, our findings demonstrated the first-day dynamic change in antithrombin activity, and not the basal level, to be able to predict critically ill patient death. This dynamic change was associated with an improvement in the platelet counts, fibrinogen levels, and the DIC score. Am. J. Hematol. 81:907-914, 2006.Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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First day dynamic changes in antithrombin III activity after supplementation have a predictive value in critically ill patients

et al. 2006

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“…In addition, four Japanese and overseas studies395, 402, 403, 404 were analyzed. The treatment intervention was expected to be beneficial in terms of reduced mortality rate based on an RR of 0.68 (95% CI: 0.49–0.93), but bias risk/indirectness may lower the reliability of the effect estimate.…”

Section: Cq16: Diagnosis and Treatment Of Disseminated Intravascular mentioning

confidence: 99%

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

Nishida

Ogura

Egi

et al. 2018

Acute Medicine & Surgery

157

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Background and PurposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two‐thirds (>66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J‐SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta‐analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese‐specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non‐specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

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“…Antithrombin III, the main inhibitor of thrombin and factor Xa, is rapidly consumed by the ongoing thrombin formation, resulting in (very) low levels of this protease inhibitor [4]. The importance of sufficient plasma levels of antithrombin III has been shown in experimental and clinical studies [21,22]. In addition, a significant down-regulation of the protein C-protein S system may occur.…”

Section: Activation and Inhibition Of Coagulation During Endotoxaemiamentioning

confidence: 99%

The cytokine‐mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia

Levi

Poll

Cate

et al. 1997

Eur J Clin Investigation

290

174

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Abstract. Disseminated intravascular coagulation (DIC)is a frequently occurring complication of sepsis and may contribute to multiple organ failure. More insight into the pathogenesis of this derangement of the coagulation system is necessary to develop more effective therapeutic strategies for this condition. Recently, more detailed knowledge on the pathogenetic pathways involved in DIC has been obtained by the study of models of experimental bacteraemia and endotoxaemia in human subjects and non-human primates. The mechanisms that lead to activation of coagulation, potentiated by the simultaneous depression of physiological inhibitory systems and to impaired function of the fibrinolytic system, are outlined in this review. In addition, the mediatory role of various cytokines in the derangement of coagulation is discussed.

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Double-blind, Placebo-controlled Trial of Antithrombin III Concentrates in Septic Shock With Disseminated Intravascular Coagulation

Cited by 373 publications

References 20 publications

First day dynamic changes in antithrombin III activity after supplementation have a predictive value in critically ill patients

First day dynamic changes in antithrombin III activity after supplementation have a predictive value in critically ill patients

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

The cytokine‐mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia

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