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Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis.

ABSTRACT: Endothelial dysfunction plays an important role in the pathophysiology of sepsis. As previously reported, the serum thrombomodulin is elevated in diseases associated with endothelial injury.The aim of this study was to investigate the association of serum thrombomodulin level in different pediatric sepsis syndromes and evaluate the relationship with disease severity and mortality.We prospectively collected cases of sepsis treated in a pediatric intensive care unit from June 2012 to July 2015 at Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and serum thrombomodulin levels were analyzed.Increased serum thrombomodulin levels on days 1 and 3 of the diagnosis of sepsis were found in different pediatric sepsis syndromes. Patients with septic shock had significantly increased serum thrombomodulin levels on days 1 and 3 [day 1: median, 6.9 mU/ml (interquartile range (IQR): 5.8-12.8) and day 3: median, 5.8 mU/ml (IQR: 4.6-10.8)] compared to healthy controls [median, 3.4 mU/ml (IQR: 2.3-4.2)] (p = <0.001 and 0.001, respectively) and those with sepsis [day 1: median, 2.9 mU/ml (IQR: 1.8-4.7) and day 3: median, 3 mU/ml (IQR: 1.5-3.5)] and severe sepsis [day 1: median, 3.3 mU/ml (IQR: 1.3-8.6) and day 3: median, 4.4 mU/ml (IQR: 0.5-6)] (p = <0.001 and 0.001, respectively). There was also a significant positive correlation between serum thrombomodulin level on day 1 and day 1 PRISM-II, PELOD, P-MOD and DIC scores. The patients who died had significantly higher serum thrombomodulin levels on days 1 and 3 [day 1: median, 9.9 mU/ml (IQR: 6.2-15.6) and day 3: median, 10.4 mU/ml (IQR: 9.2-11.7)] than the survivors [day 1; median, 4.4 mU/ml (IQR: 2.2-7.5) and day 3: [median, 3.5 mU/ml (IQR: 1.6-5.7)] (p = 0.046 and 0.012, respectively).Increased serum thrombomodulin levels were found in different pediatric sepsis syndromes and correlated with disease severity and mortality.

SUBMITTER: Lin JJ

PROVIDER: S-EPMC5542536 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:Introduction and aimsB- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators.Methods101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study. Plasma concentrations of soluble BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) were measured with ELISA in serial blood samples. Comparisons were made with Mann-Whitney U test and correlations were assessed with Spearman's Rank correlation test. Cox proportional hazard models, with sBTLA and sPD-1 as fixed and sBTLA as time-varying covariates, were used to determine association with 28-day mortality.ResultssBTLA levels were significantly higher in the sepsis cohort (median 14 ng/mL, IQR 8-29) compared to ICU controls (9 ng/mL, IQR 5-26, p = 0.048) and HC (2.9 ng/mL, IQR 0.9-9.1, p<0.01), and correlated to SOFA score. sBTLA levels were higher in 28 day sepsis non-survivors than in survivors (baseline median 28 ng/mL, IQR 13-41 vs 13 ng/mL, IQR 8-23, p = 0.04). After adjustment for age and comorbidities, the relative risk of 28 day mortality was nearly 5-fold higher in sepsis patients with a baseline sBTLA > 21 ng/mL, compared to those with a level below this threshold. sBTLA was even more associated with mortality in the time-varying analysis. sPD-1 levels were lower in the sepsis cohort compared to HC but not compared to ICU controls and were not associated with mortality. sCTLA-4 was detectable in only one subject.ConclusionPlasma concentrations of soluble BTLA were increased early in sepsis/septic shock and correlated to severity of disease. A baseline concentration >21ng/mL was associated with a poor prognosis.

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Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis.

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