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Review
. 2024 Sep 20;14(1):148.
doi: 10.1186/s13613-024-01380-5.

Sepsis-induced coagulopathy (SIC) in the management of sepsis

Affiliations
Review

Sepsis-induced coagulopathy (SIC) in the management of sepsis

Toshiaki Iba et al. Ann Intensive Care. .

Abstract

The mortality rate of sepsis remains high and further increases when complicated by disseminated intravascular coagulation (DIC). Consequently, early detection and appropriate management of DIC will be helpful for the management of sepsis. Although overt DIC criteria are often used for diagnosing definitive DIC, it was not designed to detect early-phase DIC. The criteria and scoring system for sepsis-induced coagulopathy (SIC) were developed and introduced in 2017 to detect early-stage DIC, and they were subsequently adopted by the International Society on Thrombosis and Haemostasis in 2019. The objective of detecting SIC was not to miss the patients at high risk of developing overt DIC at an earlier time. Although anticoagulant therapies are potential options for the treatment of sepsis-associated DIC, their effectiveness has not been established, and further research is warranted. For that purpose, an international collaborative platform is required for future clinical trials, and SIC criteria have been suggested for such studies. Calculating the SIC score is straightforward and suitable for use in clinical settings. This review aims to introduce SIC criteria and its scoring system for better management of sepsis-associated DIC. We also intended to update the current knowledge regarding this novel diagnostic criterion.

Keywords: Anticoagulants; Clinical trial; Coagulopathy; Disseminated intravascular coagulation; Sepsis.

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Conflict of interest statement

TI has participated in advisory boards of Japan Blood Products Organization, Toray Medical, and Asahi Kasei Pharmaceuticals and received a research grant from JIMRO. JH has received honoraria from Asahi Kasei, Diagnostica Stago, Pfizer PFE France and Sanofi Aventis France, MSD, Shionogi, and Inotrem. JHL serves on the Steering Committees for Merck, Octapharma, and Werfen. TI and JHL were instrumental in the creation and dissemination of the SIC and SIC scoring system. JH is an Editorial Board member of this journal.

Figures

Fig. 1
Fig. 1
Antithrombogenicity in physiological status and prothrombotic shift in sepsis-induced coagulopathy The vascular endothelial cells maintain the antithrombotic condition by producing nitric oxide (NO) and prostaglandin I2 (PGI2). Antithrombin/heparan sulfate of the endothelial glycocalyx contributes to the antithrombogenicity of the luminal surface. Thrombomodulin (TM) on the surface of endothelial cells converts protein C (PC) to activated protein C (APC) and exerts antithrombotic activity. This antithrombotic condition turns to the opposite in sepsis-induced coagulopathy (SIC). Monocyte expresses tissue factor (TF) and initiates the extrinsic coagulation cascade, and exposed collagen beneath the endothelium initiates the intrinsic coagulation cascade. Activated neutrophils eject neutrophil extracellular traps (NETs) and further propagate coagulation and inflammation. Platelets also participate in thrombus formation by releasing von Willebrand factor (VWF) and platelet factor 4 (PF4). Damaged endothelium releases VWF, angiopoietin 2 (Ang2), and expresses adhesion molecules that facilitate cellular attachment. Endothelial cells produce excess plasminogen activator inhibitor 1 (PAI-1) and suppress fibrinolysis
Fig. 2
Fig. 2
Progression from sepsis to disseminated intravascular coagulation Inflammation and coagulation are the major drivers of disease progression in sepsis. Patients progress from sepsis-induced coagulopathy (SIC), an early-phase disseminated intravascular coagulation (DIC), to overt, late-phase DIC. Multiple risk factors are known to facilitate disease progression and increase the risk of death. The Japanese Association for Acute Medicine (JAAM) DIC criteria is also designed to diagnose early-phase DIC; however, it does not overlap with SIC
Fig. 3
Fig. 3
Time course of coagulopathy and application of the anticoagulant therapy The presence or absence of sepsis-induced coagulopathy (SIC) is assessed in the emergency room (ER). In cases where septic patients are complicated by SIC, the test should be repeated daily. If SIC persists or coagulopathy worsens to overt disseminated intravascular coagulation (DIC), integrated management, including anticoagulant therapy, should be considered

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