Diagnostic and prognostic utility of tissue factor for severe sepsis and sepsis-induced acute lung injury.

Mingming Xue,Yuxin Wang,Zhi Deng,Chenling Yao,Zhan Sun,Lingyu Xing,Si Sun,Jun Yin,Jin Zhang,Zhenju Song,Mian Shao,Xun Chu,Yi Han,Bin Chen,Chaoyang Tong,Xiaoliang Yang,Zhimin Dong

doi:10.1186/s12967-015-0518-9

Abstract

BackgroundTissue factor (TF) and tissue factor pathway inhibitor (TFPI) play a central role in the endothelial permeability regulation and dysfunction, which is associated with the development of sepsis and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The aim of this study is to assess the diagnostic and prognostic values of TF and TFPI in patients with sepsis and sepsis-induced ARDS.MethodsA total of 62 patients with sepsis, 167 patients with severe sepsis and 32 healthy volunteers were enrolled in this prospective observational study. TF and TFPI levels were measured by enzyme-linked immunosorbent assay (ELISA).ResultsPatients with sepsis-induced ARDS showed significantly higher median levels of TF compared with patients without ARDS (1425.5 (1019.9 to 2595.2) pg/ml vs 916.2 (724.1 to 1618.2) pg/ml, P < 0.001), and compared with sepsis patients (943.5 (786.4 to 992.4) pg/ml, P < 0.001) on the day of admission. However, there was no significant difference between sepsis patients and healthy subjects, or between septic shock and non-septic shock patients (P > 0.05). The AUC of TF for the diagnosis of sepsis-induced ARDS was 0.749 (95% confidence interval (CI) 0.675-0.822). Plasma TF levels in the non-survivors of severe sepsis were significantly higher than those of survivors (1618.6 (1017.1 to 2900.8) pg/ml vs. 979.9 (757.2 to 1645.5) pg/ml, P < 0.001), and multivariate logistic regression showed the plasma value of TF was the independent predictor for 30-day mortality in patients with severe sepsis (P = 0.0022, odds ratio (OR) = 1.41, 95% CI 1.24-1.69). The AUC of TF for predicting 30-day mortality in severe sepsis patients was 0.718 (95% CI 0.641-0.794). However, there was no significant difference in the plasma TFPI values among the healthy control, sepsis and severe sepsis groups (P > 0.05).ConclusionsOur data showed that tissue factor is a valuable diagnostic biomarker for the diagnosis of sepsis-induced ARDS. Moreover, tissue factor is a strong prognostic marker for short-term mortality in severe sepsis and sepsis-induced ARDS patients.

Highlights

Despite advances in the development of numerous drugs and supportive care therapies, severe sepsis remains an unconquered challenge for clinical investigators and physicians with an unacceptable high mortality rate of 28% to 50%
Study population characteristics A total of 62 sepsis and 167 severe sepsis patients in the Emergency department and intensive care unit (ICU) of Zhongshan Hospital and 32 healthy controls were enrolled in this study
Severe sepsis patients were classified into Acute respiratory distress syndrome (ARDS) and non-ARDS groups, septic shock and non-septic shock groups, survivor and non-survivor groups according to the illness severity and 30-day survival

Summary

Introduction

Despite advances in the development of numerous drugs and supportive care therapies, severe sepsis remains an unconquered challenge for clinical investigators and physicians with an unacceptable high mortality rate of 28% to 50%. The pathogenesis of sepsis is not precisely understood; emerging evidence suggested that an exaggerated systemic host inflammation and coagulation response to infectious pathogens led to microvascular thrombosis and multiple organ dysfunction syndromes (MODS). In recent years, mounting empirical evidence supported that an extensive cross-talk between the inflammation and coagulation systems played a pivotal role in the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection [2]. Many clinical studies found that virtually all septic patients had coagulation abnormalities. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) play a central role in the endothelial permeability regulation and dysfunction, which is associated with the development of sepsis and acute lung injury/ acute respiratory distress syndrome (ALI/ARDS).

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