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Back to Basics: Recognition of Sepsis with New Definition
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A Systematic Summary of Systematic Reviews on Anticoagulant Therapy in Sepsis

Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka 558-8558, Japan
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Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(11), 1869; https://doi.org/10.3390/jcm8111869
Received: 28 October 2019 / Accepted: 1 November 2019 / Published: 4 November 2019
Many systematic reviews have been published regarding anticoagulant therapy in sepsis, among which there is substantial heterogeneity. This study aimed to provide an overview of existing systematic reviews of randomized controlled trials by using a comprehensive search method. We searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. Of 895 records screened, 19 systematic reviews were included. The target agent was as follows: antithrombin (n = 4), recombinant thrombomodulin (n = 3), heparin (n = 3), recombinant activated protein C (n = 8), and all anticoagulants (n = 1). Antithrombin did not improve mortality in critically ill patients but indicated a beneficial effect in sepsis-induced disseminated intravascular coagulation (DIC), although the certainty of evidence was judged as low. Recombinant thrombomodulin was associated with a trend in reduced mortality in sepsis with coagulopathy with no increased risk of bleeding, although the difference was not statistically significant and the required information size for any declarative judgement insufficient. Although three systematic reviews showed potential survival benefits of unfractionated heparin and low-molecular-weight heparin in patients with sepsis, trials with low risk of bias were lacking, and the overall impact remains unclear. None of the meta-analyses of recombinant activated protein C showed beneficial effects in sepsis. In summary, a beneficial effect was not observed in overall sepsis in poorly characterized patient groups but was observed in sepsis-induced DIC or sepsis with coagulopathy in more specific patient groups. This umbrella review of anticoagulant therapy suggests that characteristics of the target populations resulted in heterogeneity among the systematic reviews. View Full-Text
Keywords: sepsis; disseminated intravascular coagulation; coagulopathy; anticoagulant; antithrombin; thrombomodulin; heparin; recombinant activated protein C; umbrella review; systematic review sepsis; disseminated intravascular coagulation; coagulopathy; anticoagulant; antithrombin; thrombomodulin; heparin; recombinant activated protein C; umbrella review; systematic review
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Murao, S.; Yamakawa, K. A Systematic Summary of Systematic Reviews on Anticoagulant Therapy in Sepsis. J. Clin. Med. 2019, 8, 1869.

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