Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients

Abstract

Objective: The aim of this study is to evaluate the association between burn injury and admission plasma levels of Syndecan-1 (SDC-1) and Tissue Factor Pathway Inhibitor (TFPI), and their ability to predict 30-day mortality. Background: SDC-1 and TFPI are expressed by vascular endothelium and shed into the plasma as biomarkers of endothelial damage. Admission plasma biomarker levels have been associated with morbidity and mortality in trauma patients, but this has not been well characterized in burn patients. Methods: This cohort study enrolled burn patients admitted to a regional burn center between 2013 and 2017. Blood samples were collected within 4 h of admission and plasma SDC-1 and TFPI were quantified by ELISA. Demographics and injury characteristics were collected prospectively. The primary outcome was 30-day in-hospital mortality. Results: Of 158 patients, 74 met inclusion criteria. Most patients were male with median age of 41.5 years and burn TBSA of 20.5%. The overall mortality rate was 20.3%. Admission SDC-1 and TFPI were significantly higher among deceased patients. Plasma SDC-1 >34 ng/mL was associated with a 32-times higher likelihood of mortality [OR: 32.65 (95% CI, 2.67–399.78); P = 0.006] and a strong predictor of mortality (area under the ROC [AUROC] 0.92). TFPI was associated with a nine-times higher likelihood of mortality [OR: 9.59 (95% CI, 1.02–89.75); P = 0.002] and a fair predictor of mortality (AUROC 0.68). Conclusions: SDC-1 and TFPI are associated with a higher risk of 30-day mortality. We propose the measurement of SDC-1 on admission to identify burn patients at high risk of mortality. However, further investigation with a larger sample size is warranted.

The Impact of Anticoagulant Activity of Tissue Factor Pathway Inhibitor Measured by a Novel Functional Assay for Predicting Deep Venous Thrombosis in Trauma Patients: A Prospective Nested Case-Control Study

“…We found that the anticoagulant activity of TFPI in trauma patients was significantly higher than that in healthy controls, a finding consistent with the results of Keyloun's study. 13 The reason for the increased anticoagulant activity of TFPI in patients with trauma may be related to extensive injury of vascular endothelial cells and inflammation caused by traumatic fractures. There is no doubt that traumatic fracture as an external force leads to endothelial cell activation and injury.…”

“…These results suggest that full-length TFPI in plasma may be a marker of endothelial cell dysfunction. Basic experiments carried out by Zhao et al 30 found that TFPI can reduce endothelial cell injury by inhibiting endothelial autophagy and the class III PI3K/Beclin-1 pathway, while in clinical studies, Keyloun et al 13 used TFPI as a biomarker of endothelial injury and showed that the high level of TFPI in burn patients was related to a nine-fold increase in mortality (OR:9.59), and provided a predictive index of burn mortality. On the other hand, the inflammation caused by trauma has always been the focus of research attention, with studies showing that the levels of pro-inflammatory factors in plasma of post-traumatic patients were increased significantly.…”

“…While studies have reported that the antigen level of TFPI is related to venous thrombosis and the low antigen levels are a risk factor for venous thrombosis, 12 patients with trauma contrastingly have high levels of the antigen. 13,14 The reason for this increase in TFPI levels in trauma patients with DVT is not clear. At present, the majority of studies on TFPI focus on antigen levels, 15,16 a parameter, which for a number of reasons, does not provide a measure of TFPI anticoagulant activity in vivo .…”

Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)

“…This provides a new perspective on other research to understand the interaction between glycocalyx and neutrophils [ 8 ]. Other studies have shown that glycocalyx dysfunction may be associated with vascular leakage due to burns [ 9–13 ]. This suggests that there may be different interactions between neutrophils and glycocalyx in different disease settings.…”

Inhalation Injury Is Associated With Endotheliopathy and Abnormal Fibrinolytic Phenotypes in Burn Patients: A Cohort Study

“…Previous studies have shown that burn and nonburn trauma patients with high admission SDC-1 levels experience increased morbidity and mortality. 20 , 21 Concomitant IHI probably contributes to the presence and severity of endotheliopathy and coagulopathy in burns. The objective of this study was to examine the association between IHI, endothelial dysfunction, coagulation homeostasis, and clinical outcomes.…”