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

Lin, Jainn-Jim; Hsiao, Hsiang-Ju; Chan, Oi-Wa; Wang, Yu; Hsia, Shao‐Hsuan; Chiu, Cheng-Hsun

doi:10.1371/journal.pone.0182324

Cited by 25 publications

(38 citation statements)

References 17 publications

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“…TM concentrations are also higher in lethal cases of sepsis than in surviving patients (Boldt et al 1995;Lin et al 2008). Serum thrombomodulin concentrations were found to be increased in different paediatric sepsis syndromes and were correlated with the severity and mortality of the disease (Lin et al 2017). In the present study, the concentration of plasma TM in calves with sepsis was significantly higher than in the control group (P < 0.01) ( Table 3).…”

Section: Discussionsupporting

confidence: 55%

“…Numerous studies have been conducted so far on the role of biomarkers such as TM and PTX3 in human patients with sepsis but there is no report on livestock. The studies conducted on humans and laboratory animals have identified elevated TM concentrations in conjunction with disease processes that cause haemostatic disorders and endothelial damage (Ohdama et al 1994;Wu et al 2016;Lin et al 2017). TM binds to highmobility group box 1 protein and thereby prevents activation of leucocytes under in vitro conditions and lipopolysaccharide-induced lethality under in vivo conditions (Abeyama et al 2005).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of thrombomodulin and pentraxin-3 as diagnostic biomarkers in calves with sepsis

Aygun¹,

Yıldız²

2018

Vet. Med.

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Early diagnosis and treatment of sepsis in patients are crucial for their survival and can help reduce mortality rates. Novel biomarkers, such as thrombomodulin and pentraxin-3, have been used as diagnostic, prognostic and mortality indicators in patients with sepsis. Plasma thrombomodulin is a vascular endothelial membrane-bound glycoprotein and pentraxin-3 is an acute-phase protein. In the present study, thrombomodulin and pentraxin-3 levels were determined in calves with sepsis, to determine their diagnostic values as well as usefulness as indicators of health status. To this end, 20 neonatal calves with sepsis (G1) and ten healthy neonatal calves (G2) were used. Additionally, group G1 was also divided into two groups consisting of surviving (G1-S; n = 9) and non-surviving calves (G1-NS; n = 11). A single blood sample was collected from all the calves and the prepared serum samples were used to measure thrombomodulin and pentraxin-3 levels using bovine-specific ELISA kits. The serum concentrations of thrombomodulin and pentraxin-3 were found to be significantly higher (P < 0.01) in the G1 group than in G2. Thrombomodulin and pentraxin-3 levels were also found to be higher in the G1-NS group than in G1-S but the difference was not significant. We conclude that thrombomodulin and pentraxin-3 may have some diagnostic value in calves with sepsis. Furthermore, these findings may also help in understanding the pathogenesis of sepsis in neonatal calves. Further studies are required to determine the importance of thrombomodulin and pentraxin-3 as diagnostic and prognostic biomarkers in calves with sepsis and to evaluate the concentrations of these biomarkers also in other disease states.Keywords: haematology; leucocytosis; biomarker; acute-phase protein; neonatal calves List of abbreviations CRP = C-reactive protein, CRT = capillary refill time, DIC = disseminated intravascular coagulation, GRA = granulocyte, HCT = haematocrit, MAP = mean arterial pressure, PLT = platelet, PTX3 = pentraxin-3, RBC = red blood cell, SEM = standard error of the mean, SpO 2 = peripheral oxygen saturation, TLR = toll-like receptor, TM = thrombomodulin, WBC = white blood cell

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Evaluation of thrombomodulin and pentraxin-3 as diagnostic biomarkers in calves with sepsis

Aygun¹,

Yıldız²

2018

Vet. Med.

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“…There were no differences between thrombomodulin levels in type I and type II, which is in agreement with previous reports demonstrating high levels of soluble thrombomodulin in bacterial infections regardless of the causative microorganism (34,35). Moreover, elevated concentrations of thrombomodulin in blood have been reported in patients with sepsis (35)(36)(37)(38). Such elevated levels were also detected in the sepsis cohort we included during the validation stage.…”

Section: Discussionsupporting

confidence: 91%

“…Notably, thrombomodulin retained its discriminatory power for NSTIs. Finally, thrombomodulin has also been proposed as a biomarker for the prediction of mortality in patients with sepsis ( 35 , 37 ) and septic shock ( 39 ). Although an association with mortality in NSTI was not noted in our study, a weak association with septic shock was identified.…”

Section: Discussionmentioning

confidence: 99%

Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections

Medina¹,

Rath²,

Jahagirdar³

et al. 2021

Journal of Clinical Investigation

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These infections are infrequent, but are associated with a significant health burden due to high mortality and risk of severe long-term disability as a consequence of extensive tissue loss or amputations (3)(4)(5). The progression of the disease is rapid, and early identification is therefore pivotal for improving the prognosis of affected patients. Currently, the initial diagnosis of NSTI is challenging due to the often vague symptoms during early stages, a heterogeneous patient group, and lack of specific diagnostic tools (6), which lead to misdiagnoses of NSTI in many cases (7). Still, doctors are advised that in case of NSTI suspicion, patients should be referred to surgical evaluation immediately (8). Previous efforts to improve the diagnosis of NSTIs led to the proposal of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) CONCLUSIONS. This study identifies predictive biomarkers for NSTI clinical phenotypes of potential value for diagnostic, prognostic, and therapeutic approaches in NSTIs. TRIAL REGISTRATION. ClinicalTrials.gov NCT01790698.

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“…Another risk factor of 90-day mortality that emerged as particularly important for prediction was elevated thrombomodulin level. Thrombomodulin, an integral endothelial cell membrane protein, is cleaved and released into the bloodstream during sepsis and septic shock [26,27], leading to elevated levels of serum thrombomodulin in pediatric and adult sepsis patients [28,29]. Endothelium is the primary site of damage in sepsis due to massive production of proin ammatory cytokines [30].…”

Section: Discussionmentioning

confidence: 99%

Prediction of 90-day mortality among sepsis patients based on a nomogram integrating diverse clinical indices

Zeng¹,

He²,

Zhang³

et al. 2021

Preprint

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Background Sepsis is prevalent among intensive care units and is a frequent cause of death. Several studies have identified individual risk factors or potential predictors of sepsis-associated mortality, without defining an integrated predictive model. The present work aimed to define a nomogram for reliably predicting mortality. Methods We carried out a retrospective, single-center study based on 231 patients with sepsis who were admitted to our intensive care unit between May 2018 and October 2020. Patients were randomly split into training and validation cohorts. In the training cohort, multivariate logistic regression and a stepwise algorithm were performed to identify risk factors, which were then integrated into a predictive nomogram. Nomogram performance was assessed against the training and validation cohorts based on the area under receiver operating characteristic curves (AUC), calibration plots and decision curve analysis. Results Among the 161 patients in the training cohort and 70 patients in the validation cohort, 90-day mortality was 31.6%. Older age and higher values for the international normalized ratio, lactate level, and thrombomodulin level were associated with greater risk of 90-day mortality. The nomogram showed an AUC of 0.810 (95% CI 0.739 to 0.881) in the training cohort and 0.813 (95% CI 0.708 to 0.917) in the validation cohort. The nomogram also performed well based on the calibration curve and decision curve analysis. Conclusion This nomogram may help identify sepsis patients at elevated risk of 90-day mortality, which may help clinicians allocate resources appropriately to improve patient outcomes.

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

Cited by 25 publications

References 17 publications

Evaluation of thrombomodulin and pentraxin-3 as diagnostic biomarkers in calves with sepsis

Evaluation of thrombomodulin and pentraxin-3 as diagnostic biomarkers in calves with sepsis

Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections

Prediction of 90-day mortality among sepsis patients based on a nomogram integrating diverse clinical indices

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