Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

Xing, Katharine He; Murthy, Srinivas; Liles, W. Conrad; Singh, Jeffrey M.

doi:10.1186/cc11145

Cited by 122 publications

(117 citation statements)

References 94 publications

(234 reference statements)

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“…Our results demonstrate that hemostasis-related parameters have a significant impact on severity and outcome prediction of patients with sepsis, since endothelial and coagulation dysfunction is essential in pathophysiology of sepsis (19)(20)(21).…”

Section: Discussionmentioning

confidence: 94%

Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis

Mihajlović¹,

Lendak²,

Mitić³

et al. 2015

Turk J Med Sci

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Background/aim: Clinical manifestations of sepsis are not caused directly by the invading pathogens, but rather mostly by systemic inflammation that leads to activation of the coagulation system. The aim of this study was to determine whether levels of hemostasisrelated parameters measured in intensive care unit admissions are associated with mortality and severity in patients with sepsis.Materials and methods: Eighty-five patients who fulfilled criteria for a diagnosis of sepsis were included in our study. Platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time, D-dimer, and fibrinogen levels were determined within the first 24 h from sepsis onset. Differences between groups of septic patients were assessed by Mann-Whitney U test and Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors.Results: Prolonged aPTT and PT with higher D-dimer concentrations in patients with sepsis are associated with more severe forms of the disease. aPTT was prolonged in nonsurvivors, while platelet count and fibrinogen levels were higher in survivors. Platelet count and aPTT ratio are independent predictors of fatal outcome in our logistic regression model. Conclusion:Hemostasis-related parameters have a significant impact on severity and outcome in sepsis.

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Section: Discussionmentioning

confidence: 94%

Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis

Mihajlović¹,

Lendak²,

Mitić³

et al. 2015

Turk J Med Sci

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“…Recently, a meta-analysis [23] revealed three studies that showed ADAMTS13 was significantly lower in sepsis than other critically ill non-septic patients [14,19,24].…”

Section: Discussionmentioning

confidence: 99%

“…These include regulators of endothelial activation, vWF and ADAMTS13 [9]. In 1996, a protease that was able to cleave VWF [10,11]was described and, in 2001, Zheng et al [12] named this protease ADAMTS13 (the 13th member of A Disintegrin-like And Metalloprotease with ThromboSpondin type 1 motif, member 13).…”

mentioning

confidence: 99%

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

Azfar

Khan

Habib

et al. 2017

CIM

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Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock Abstract Purpose: ADAMTS13 level was evaluated as a predictor of mortality in patients with severe sepsis and septic shock, and compared with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores.Methods: This prospective observational study was conducted in the Medical and Surgical Intensive Care Units of King Khalid University Hospital. Detailed clinical evaluations were performed on 84 patients (56.08±18.18 years of age) with severe sepsis and septic shock. ADAMTS13 levels were determined (three blood samples at 24 hours intervals) and APACHE II scores, hematological profiles, indices of organ hypo-perfusion, renal functions and coagulation profiles were recorded. Primary outcome was 30 days ICU mortality and secondary outcomes were its comparison with APACHE II score, length of ICU stay and use of vasopressor agents.Results: Hypertension (53.6%) and diabetic mellitus (45.2%) were the commonest comorbidities. The median ADAMTS13 levels were 336.65, 339.35 and 313.9, respectively. ROC analysis showed maximum area under the curve for second ADAMTS13 (AUC=0.760) compared with first (AUC=0.660) and third samples (AUC=0.707) and APACHE II scores (AUC=0.662). Patients were divided into low and high ADAMTS13 groups according to the best cut-off point. Mortality was high in the low ADAMTS13 level group [OR=4.5]and was significantly associated with age, DBP, ADAMTS13, APACHE II score, DIC score and platelet count. ADAMTS13 (OR=5.3), APACHE II (OR=4.13) and DIC scores (OR=7.32) were significant risk factors for mortality.Conclusions: Low ADAMTS13 was associated with increased mortality in patients with severe sepsis and septic shock and was comparable to APACHE II scores for predicting mortality.

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“…We chose to focus on the vascular effector proteins, VEGF, VCAM-1, and endostatin (Fig. 2), since vascular endothelial inflammation is a key feature of MOF syndromes (20,23,40). Protein levels of VEGF were found to be significantly elevated in both VILI and CLPϩVILI compared with sham (P Ͻ 0.001 and P Ͻ 0.05, respectively) and CLP kidneys (P Ͻ 0.001 and P Ͻ 0.01, respectively) by Western blot analysis.…”

Section: Mediators Of Vascular Endothelial Inflammation Are Increasedmentioning

confidence: 99%

Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney

Hepokoski

Englert

Baron

et al. 2017

American Journal of Physiology-Renal Physiology

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In critical illness, such as sepsis or the acute respiratory distress syndrome, acute kidney injury (AKI) is common and associated with increased morbidity and mortality. Mechanical ventilation in critical illnesses is also a risk factor for AKI, but it is potentially modifiable. Injurious ventilation strategies may lead to the systemic release of inflammatory mediators from the lung due to ventilator induced lung injury (VILI). The systemic consequences of VILI are difficult to differentiate clinically from other systemic inflammatory syndromes, such as sepsis. The purpose of this study was to identify unique changes in the expression of inflammatory mediators in kidney tissue in response to VILI compared with systemic sepsis to gain insight into direct effects of VILI on the kidney. Four groups of mice were compared—mice with sepsis from cecal ligation and puncture (CLP), mice subjected to injurious mechanical ventilation with high tidal volumes (VILI), mice exposed to CLP followed by VILI (CLP+VILI), and sham controls. Protein expression of common inflammatory mediators in kidneys was analyzed using a proteome array and confirmed by Western blot analysis or ELISA. VEGF and VCAM-1 were found to be significantly elevated in kidneys from VILI mice compared with sham and CLP. Angiopoietin-2 was significantly increased in CLP+VILI compared with CLP alone and was also correlated with higher levels of AKI biomarker, neutrophil gelatinase-associated lipocalin. These results suggest that VILI alters the renal expression of VEGF, VCAM-1, and angiopoietin-2, and these proteins warrant further investigation as potential biomarkers and therapeutic targets.

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Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

Cited by 122 publications

References 94 publications

Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis

Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney

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