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Angiopoietin‐2 levels in the risk stratification and mortality outcome prediction of sepsis associated coagulopathy
Author(s) -
Statz Steve,
Walborn Amanda,
Williams Mark,
Hoppensteadt Debra,
Mosier Michael,
Rondina Matthew,
Fareed Jawed
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb494
Subject(s) - medicine , sepsis , coagulopathy , angiopoietin , angiopoietin 2 , gastroenterology , biomarker , cohort , disseminated intravascular coagulation , vascular endothelial growth factor , biology , biochemistry , vegf receptors
Background Angiopoietin‐2 (Ang‐2) is a 70 kDa glycoprotein which plays multiple roles in angiogenesis, inflammation, and vascular development. Ang‐2 is upregulated in vascular stress, and circulates at high levels in certain pathologic conditions such as sepsis. Ang‐2 upregulation may be related to the severity of sepsis associated coagulopathy (SAC), and therefore it may have a predictive role in the clinical outcome of this syndrome. Aim The aim of this study is to measure Ang‐2 levels in a defined cohort of patients with sepsis and suspected disseminated intravascular coagulation (DIC), to compare the circulating levels of this biomarker to controls, and to demonstrate its predictive value for the clinical outcome and severity of SAC. Methods Plasma samples were collected from 102 patients with sepsis and suspected DIC at ICU admission and immediately frozen at −80°C for batch analysis. Control plasma represented 50 normal samples which were commercially obtained from George King (Orland Park, KS). Ang‐2 levels were quantified using a sandwich ELISA method (R&D Systems, Minneapolis, MN, USA). This method employs a monoclonal antibody specific for human Ang‐2. DIC scores in all 102 patients were evaluated using the ISTH scoring algorithm. Results Table 1 shows that in comparison to normal levels, the samples collected from all patients showed significantly higher levels of Ang‐2 for all groups (p=0.0005). Table 2 shows that the Ang‐2 levels were also significantly different between the survivors and non‐survivors for 28‐day mortality outcome by the Mann‐Whitney test (p=0.001). Conclusion This study demonstrates that Ang‐2 levels are significantly upregulated in SAC, and this biomarker can be used to risk stratify the severity of this disease. Ang‐2 level can also be used to differentiate non‐overt and overt DIC. Furthermore, Ang‐2 level at the time of initial diagnosis provides a predictive biomarker for mortality outcome. 1 Ang‐2 levels in patients with Sepsis and Suspected DIC Broken Down by ISTH DIC ScoreCategory Normals + Sepsis−DIC + Sepsis + Non‐Overt DIC + Sepsis + Overt DIC ISTH DIC Score N/A 0–2 3–4 ≥ 5n 50 20 57 24 Ang‐2 Mean ± SEM (ng/mL) 1.87 ± 0.15 8.34 ± 2.50 11.53 ± 1.40 29.44 ± 6.27 Ang‐2 Std. Deviation (ng/mL) 1.07 11.19 10.54 30.732 Significant Difference in Ang‐2 Level Between Survivors and Non‐SurvivorsSurvivors Non‐Survivorsn 86 15 Ang‐2 Mean ± SEM (ng/mL) 12.54 ± 1.54 30.17 ± 8.62 Ang‐2 Std. Deviation (ng/mL) 14.28 33.39