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

Abstract

Background: 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). 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.

Methods: A 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).

Results: Patients 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).

Conclusions: Our 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.

Fig. 1

The plasma values of TF in different subgroup patients with severe sepsis. Patients with sepsis-induced ARDS had significantly higher median levels of TF compared with patients without ARDS at the time of diagnosis (P < 0.001), however there was no significant difference between septic shock and non-septic shock groups. The TF plasma values in the non-survivors of severe sepsis were significant higher than those in the survivors (P < 0.001)

Fig. 2

The ROC curve for TF in relation to the diagnosis of sepsis-induced ARDS. The AUC for TF in relation to the diagnosis of sepsis-induced ARDS from non-ARDS patients was 0.749 (95% CI 0.675-0.822)

Fig. 3

The plasma levels of TF on the 1st, 3rd, 7th day of sepsis-induced ARDS patients. On the day of admission, the TF plasma levels in non-survivors of ARDS patients were significantly elevated compared with those in survivors of ARDS patients (P = 0.00013). The TF levels in ARDS survivor were declined obviously on the 3rd and 7th day; however, the TF values in the non-survivors were increased continually on the 3rd and 7th day

Fig. 4

The ROC curve for TF, APACHE II in relation to the outcome of severe sepsis patients. The AUC of TF for predicting 30-day mortality in septic patients was 0.718, slightly lower than that of APACHE II scores 0.804. The AUC of TF in combination with the APACHE II scores was 0.832, which was more statistically significant compared with TF alone

Fig. 5

The survival probability of severe sepsis patients by TF value. A Kaplan-Meier curve was drawn according to the value of 1033.9 pg/ml for TF as a cutoff point to describe death over 30 days of follow-up