scholarly journals Angiopoietin 2 Levels in the Risk Stratification and Mortality Outcome Prediction of Sepsis-Associated Coagulopathy

2018 ◽  
Vol 24 (8) ◽  
pp. 1223-1233 ◽  
Author(s):  
Stephen Statz ◽  
Giselle Sabal ◽  
Amanda Walborn ◽  
Mark Williams ◽  
Debra Hoppensteadt ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Predictive Biomarker ◽  
Illness Severity ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Icu Admission ◽  
Severity Scores ◽  
Mortality Outcome ◽  
Clinical Illness ◽  
Angiopoietin 2

It has been well established that angiopoietin 2 (Ang-2), a glycoprotein involved in activation of the endothelium, plays an integral role in the pathophysiology of sepsis and many other inflammatory conditions. However, the role of Ang-2 in sepsis-associated coagulopathy (SAC) specifically has not been defined. The aim of this study was to measure Ang-2 plasma levels in patients with sepsis and suspected disseminated intravascular coagulation (DIC) in order to demonstrate its predictive value in SAC severity determination and 28-day mortality outcome. Plasma samples were collected from 102 patients with sepsis and suspected DIC at intensive care unit (ICU) admission. The Ang-2 plasma levels were quantified using a sandwich enzyme-linked immunosorbent assay method. The International Society on Thrombosis and Haemostasis DIC scoring system was used to compare the accuracy of Ang-2 levels versus clinical illness severity scores in predicting SAC severity. Mean Ang-2 levels in patients with sepsis and DIC were significantly higher in comparison to healthy controls ( P < 0.0001), and median Ang-2 levels showed a downward trend over time ( P = 0.0008). Baseline Ang-2 levels and clinical illness severity scores were higher with increasing severity of disease, and Ang-2 was a better predictor of DIC severity than clinical illness scores. This study demonstrates that Ang-2 levels are significantly upregulated in SAC, and this biomarker can be used to risk stratify patients with sepsis into non-overt DIC and overt DIC. Furthermore, the Ang-2 level at ICU admission in a patient with sepsis and suspected DIC may provide a predictive biomarker for mortality outcome.

scholarly journals Evaluation of Expression Level of Apolipoprotein M as a Diagnostic Marker for Primary Venous Thromboembolism

2017 ◽  
Vol 24 (3) ◽  
pp. 416-422
Author(s):  
Abrar Ahmad ◽  
Kristina Sundquist ◽  
Bengt Zöller ◽  
Björn Dahlbäck ◽  
Johan Elf ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Plasma Levels ◽  
Assay Method ◽  
First Episode ◽  
Enzyme Linked Immunosorbent Assay ◽  
Apolipoprotein M ◽  
Score Study ◽  
Diagnostic Role ◽  
Male Patients

Recently, decreased levels of apolipoprotein M (ApoM) were shown to be associated with higher risk of recurrent venous thromboembolism (VTE) in male patients. However, the role of ApoM in primary VTE is unknown. We aimed in our study to analyze the plasma levels of ApoM in patients with VTE in order to evaluate the diagnostic importance of ApoM in primary VTE. A total of 357 patients with suspected first episode of VTE were recruited prospectively in the SCORE study. Plasma samples from 307 patients were available for quantifying the plasma levels of ApoM in patients with VTE using sandwich enzyme-linked immunosorbent assay method. Among the whole population, plasma levels (mean [standard deviation]) of ApoM were not significantly different between patients with VTE (0.72 [0.20]) and non-VTE patients (0.72 [0.16]), P = .99. Similarly, in regression analyses, no significant association of ApoM plasma levels with the risk of VTE was found on univariate (odds ratio [OR] =1.0, 95% confidence interval [CI] 0.21-4.84, P = .99) and multivariate analysis (OR = 1.25, 95% CI = 0.19-8.34, P = .819) after adjusting for age, body mass index, and smoking. Moreover, results did not differ significantly after stratification of data according to sex ( P > .05). In this study, our results do not suggest a diagnostic role for ApoM plasma levels in patients with primary VTE. Moreover, the current study suggests that role of ApoM as a risk factor may differ for primary VTE and recurrent VTE in male patients.

scholarly journals KIF5A and the contribution of susceptibility genotypes as a predictive biomarker for multiple sclerosis

2021 ◽  
Author(s):  
Kelly Hares ◽  
K. Kemp ◽  
S. Loveless ◽  
C. M. Rice ◽  
N. Scolding ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prognostic Value ◽  
Tissue Injury ◽  
Susceptibility Gene ◽  
Predictive Biomarker ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nucleotide Polymorphisms ◽  
Risk Alleles ◽  
Severity Scores ◽  
Kinesin Superfamily

AbstractThere is increasing interest in the development of multiple sclerosis (MS) biomarkers that reflect central nervous system tissue injury to determine prognosis. We aimed to assess the prognostic value of kinesin superfamily motor protein KIF5A in MS by measuring levels of KIF5A in cerebrospinal fluid (CSF) combined with analysis of single nucleotide polymorphisms (SNPs; rs12368653 and rs703842) located within a MS susceptibility gene locus at chromosome 12q13–14 region. Enzyme-linked immunosorbent assay was used to measure KIF5A in CSF obtained from two independent biobanks comprising non-inflammatory neurological disease controls (NINDC), clinically isolated syndrome (CIS) and MS cases. CSF KIF5A expression was significantly elevated in progressive MS cases compared with NINDCs, CIS and relapsing–remitting MS (RRMS). In addition, levels of KIF5A positively correlated with change in MS disease severity scores (EDSS, MSSS and ARMSSS), in RRMS patients who had documented disease progression at 2-year clinical follow-up. Copies of adenine risk alleles (AG/AA; rs12368653 and rs703842) corresponded with a higher proportion of individuals in relapse at the time of lumbar puncture (LP), higher use of disease-modifying therapies post LP and shorter MS duration. Our study suggests that CSF KIF5A has potential as a predictive biomarker in MS and further studies into the potential prognostic value of analysing MS susceptibility SNPs should be considered.

scholarly journals Biomarker Profiling in Stage 5 Chronic Kidney Disease Identifies the Relationship between Angiopoietin-2 and Atrial Fibrillation

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 269S-276S ◽  
Author(s):  
Jack Bontekoe ◽  
Justin Lee ◽  
Vinod Bansal ◽  
Mushabbar Syed ◽  
Debra Hoppensteadt ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Strong Association ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Biomarker ◽  
Angiopoietin 2 ◽  
The Relationship ◽  
Circulating Levels

Atrial fibrillation (AF) is prevalent in nearly 27% of patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD), suggesting a strong association between these 2 pathologies. It is hypothesized that the relationship between these 2 diseases may be mediated by inflammation. Angiopoietin-2 (Ang-2), a pro-inflammatory biomarker of endothelial instability, inflammation, and vascular remodeling, is elevated in CKD5-HD and AF, yet has not been evaluated in patients with concomitant AF and CKD5-HD. The aim of this study is to analyze circulating levels of inflammatory and thrombotic biomarkers in patients with concomitant AF and CKD5-HD. Plasma levels of Ang-2 were measured via sandwich enzyme-linked immunosorbent assay method in CKD5-HD patients (n = 96), patients with AF (n = 38), and controls (n = 50). Angiopoietin-2 was markedly elevated in CKD5-HD with comorbid AF as compared to CKD5-HD alone, and AF alone, respectively (13.05 ± 1.56 vs 9.57 ± 0.71 ng/mL; P = .00169; vs 2.48 ± 0.57 ng/mL; P < .0001). The results of this study suggest an additive effect of Ang-2 with coexistence of AF and CKD5-HD, which may be useful in the detection of AF within this patient population.

scholarly journals Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia

Blood ◽  
2010 ◽  
Vol 116 (4) ◽  
pp. 584-592 ◽  
Author(s):  
Rossana Maffei ◽  
Silvia Martinelli ◽  
Rita Santachiara ◽  
Davide Rossi ◽  
Carla Guarnotta ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Variable Region ◽  
Lymphocytic Leukemia ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chain Gene ◽  
Small Series ◽  
Time To First Treatment ◽  
Angiopoietin 2

Abstract The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive of reduced TTFT (P < .001) and overall survival (P = .002). Multivariate analysis confirmed that high Ang2 was an independent prognosticator for TTFT (hazard ratio = 1.739; 95% confidence interval, 1.059-2.857; P = .029). Significant associations were found between high Ang2 and advanced Binet stages (P < .001), high β2-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and ζ-chain-associated protein kinase 70 expression (P < .001 and P = .003), and intermediate/high cytogenetic risk (P = .005). Moreover, Ang2 added prognostic power to other conventional prognosticators and helped to refine prognosis among CLL subsets with both high and low vascular endothelial growth factor plasma levels. Ang2 plasma level may be a useful independent prognosticator for CLL.

scholarly journals PO 8356 ANGIOGENIC AND ANGIOSTATIC FACTORS IN THE SALIVA OF MALARIA PATIENTS

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A29.2-A29
Author(s):  
Cecilia Lekpor ◽  
Felix Botchway ◽  
Jonathan Stiles ◽  
Wilson O Nana
Keyword(s):  
Plasma Levels ◽  
Predictive Biomarker ◽  
Detection Methods ◽  
Host Responses ◽  
Inflammatory Factors ◽  
P Value ◽  
Non Invasive ◽  
Increased Risk ◽  
Angiopoietin 2 ◽  
Malaria Severity

BackgroundMalaria mortality is associated with exaggerated host responses to inflammatory factors such as C-X-C motif chemokine 10 (CXCL10) and host biomarkers such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2). The aim of this study was to determine saliva levels of CXCL10, Ang-1 and Ang-2 and compare with plasma levels regarding their potential as biomarkers of malaria, which may be useful for further development of highly efficient non-invasive malaria detection methods.MethodsCase control study involving 213 subjects (119 with and 94 without malaria) aged 1–16 years. Haematological determination was done using Haematology Analyser. Plasmodium Lactate Dehydrogenase/Histidine Rich Protein-2 (pLDH/HRP-2) Antigen rapid diagnostic test (RDT) were performed. Plasma and saliva levels of CXCL10, Ang-1 and Ang-2 were measured using Elisa kit. Data was presented as mean ±standard error or median and interquartile range (IQR). A p-value<0.001 was considered statistically significant.ResultsThere was decreased plasma levels of Ang-1 and increased plasma levels of CXCL10 and Ang-2 in individuals with malaria compared to those without malaria (Ang-1, p<0.009; Ang-2, p<0.001; CXCL10 p<0.001). Biomarker levels in both plasma and saliva in subjects with malaria and without malaria were correlated and a significant relationship was found between Ang −2 and CXCL10 which could be used to predict malaria severity (p=0.001 for Ang-2 and p<0.01 for CXCL10). Low Ang-1 and high Ang-2 in both plasma and saliva were significantly associated with increased risk of malaria severity: Ang-1, 2741.04 (1785.85–3582.68), p<0.009; Ang-2, 3508.82 (2139.61–5091.633.9), p<0.001 and Ang-1, 720.27 (439.82–1086.74); 16.98 (10.08–33.26), (p<0.001 for all). Finally, Ang-2 was informative when combined with CXCL10 to predict malaria severity.ConclusionThese results provide insight into the use of saliva for a non-invasive diagnostic method and demonstrate that Ang-2 combined with CXCL10 is a promising predictive biomarker of malaria severity.

Severe Inherited “Homozygous” Protein C Deficiency in a Newborn Infant

1984 ◽  
Vol 52 (01) ◽  
pp. 053-056 ◽  
Author(s):  
A Estellés ◽  
I Garcia-Plaza ◽  
A Dasí ◽  
J Aznar ◽  
M Duart ◽  
...  
Keyword(s):  
Newborn Infant ◽  
Protein C ◽  
Skin Lesions ◽  
Fresh Frozen Plasma ◽  
Clinical Syndrome ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein C Deficiency ◽  
Fresh Frozen ◽  
Frozen Plasma

SummaryA relapsing clinical syndrome of skin lesions and disseminated intravascular coagulation (DIC) that showed remission with the infusion of fresh frozen plasma is described in a newborn infant with homozygous deficiency of protein C antigen.This patient presented since birth a recurrent clinical picture of DIC and ecchymotic skin lesions that resembled typical ecchymosis except for the fact that they showed immediate improvement with the administration of fresh frozen plasma. Using an enzyme linked immunosorbent assay method, the determination of protein C antigen levels in the patient, without ingestion of coumarin drugs, showed very low values (<1%).No other deficiencies in the vitamin-K-dependent factors or in anti thrombin III, antiplasmin, and plasminogen were found. Seven relatives of the infant had heterozygous deficiency in protein C antigen (values between 40-55%), without clinical history of venous thrombosis. The pedigree analysis of this family suggests an autosomal recessive pattern of inheritance for the clinical phenotype, although an autosomal dominant pattern has been postulated until now in other reported families.We conclude that our patient has a homozygous deficiency in protein C and this homozygous state may be compatible with survival beyond the neonatal period.

Removal of elevated circulating angiopoietin-2 by plasma exchange – A pilot study in critically ill patients with thrombotic microangiopathy and anti-glomerular basement membrane disease

2010 ◽  
Vol 104 (11) ◽  
pp. 1038-1043 ◽  
Author(s):  
Carsten Hafer ◽  
Jan Kielstein ◽  
Marion Haubitz ◽  
Hermann Haller ◽  
Svjetlana Lovric ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Plasma Exchange ◽  
Critically Ill ◽  
Glomerular Basement Membrane ◽  
Critically Ill Patients ◽  
Plasma Levels ◽  
Vascular Inflammation ◽  
Endothelial Damage ◽  
Healthy Controls ◽  
Angiopoietin 2

SummaryIn critically ill patients, the massive release of angiopoietin-2 (Ang-2) from Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2 signalling in endothelial cells, thus leading to vascular inflammation and subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is efficient for lowering excess Ang-2 levels in critically ill patients with thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti-GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four PE sessions. Twenty apparently healthy volunteers served as controls. Median (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3 (2.4–21.1) ng/ml) and anti-GBM disease (5.8 (3.4–7.0) ng/ml) compared to healthy controls (1.0 (0.9–1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.62–1.62) ng/ml) and anti-GBM disease patients (0.74 (0.59–3.62) ng/ml) compared to healthy controls (2.5 (1.93–3.47) ng/ ml, p <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7 ± 19.6 % per treatment (p <0.0001), whereas low Ang-1 plasma levels remained unchanged (0.3 ± 58.5 %; p =0.147). Ang-2 levels declined to almost normal values during ≤4 PE treatments (Friedman´s test p <0.0001). PE is an effective method to remove excess circulating Ang-2. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity.

scholarly journals Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Benson J. Ouma ◽  
Paul Bangirana ◽  
John M. Ssenkusu ◽  
Dibyadyuti Datta ◽  
Robert O. Opoka ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Parental Education ◽  
Preschool Education ◽  
Kidney Injury ◽  
Malaria Episode ◽  
Enzyme Linked Immunosorbent Assay ◽  
Testing Time ◽  
Age Related ◽  
Angiopoietin 2 ◽  
The Relationship

Abstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate. Results Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. Conclusion Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.

scholarly journals Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Savino Spadaro ◽  
Alberto Fogagnolo ◽  
Gianluca Campo ◽  
Ottavio Zucchetti ◽  
Marco Verri ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Endothelial Injury ◽  
University Hospital ◽  
Intercellular Adhesion Molecule ◽  
Secondary Outcome ◽  
Intercellular Adhesion Molecule 1 ◽  
Mechanically Ventilated ◽  
Adhesion Protein ◽  
Alveolar Epithelial ◽  
Angiopoietin 2

Abstract Background Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. Methods This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. Results In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). Conclusions COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053, Date of registration: April 13, 2020

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