High plasma mid-regional pro-adrenomedullin levels in children with severe dengue virus infections

Michels, Meta; Djamiatun, Kis; Faradz, Sultana Mh; Koenders, Mieke M J F; Mast, Quirijn de; Ven, A.J.A.M. van der

doi:10.1016/j.jcv.2010.09.008

Cited by 22 publications

(13 citation statements)

References 19 publications

(12 reference statements)

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“…Angiopoietin-1 levels across different studies seem to vary more than Ang-2 levels in controls. 16,[28][29][30][31] Angiopoietin-1 levels in the controls of our study were comparable with those of other studies, which also found relatively higher Ang-1 levels. 29,30 Therefore, we suggest that relative changes in Ang-1 levels within one study may be more informative than comparing absolute Ang-1 levels between studies.…”

Section: Discussionsupporting

confidence: 91%

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Imbalance of Angiopoietin-1 and Angiopoetin-2 in Severe Dengue and Relationship with Thrombocytopenia, Endothelial Activation, and Vascular Stability

Michels¹,

Ven²,

Djamiatun³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. The pathogenesis of plasma leakage during dengue hemorrhagic fever/dengue shock syndrome (DHF/ DSS) is largely unknown. Angiopoietins are key regulators of vascular integrity: Angiopoietin-1 is stored in platelets and maintains vascular integrity, and endothelium-derived angiopoietin-2 promotes vascular leakage. We determined angiopoietin-1 and angiopoietin-2 levels in a cohort of children in Indonesia with DHF/DSS and related them to plasma leakage markers. Patients with DHF/DSS had reduced angiopoietin-1 and increased angiopoietin-2 plasma levels on the day of admission when compared with levels at discharge and in healthy controls. There was an inverse correlation between angiopoietin-1 and markers of plasma leakage and a positive correlation between angiopoietin-2 and markers of plasma leakage. Angiopoietin-1 levels followed the same trend as the soluble platelet activation marker P-selectin and correlated with platelet counts. Dengue-associated thrombocytopenia and endothelial activation are associated with an imbalance in angiopoietin-2: angiopoietin-1 plasma levels. This imbalance may contribute to the transient plasma leakage in DHF/DSS.

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Section: Discussionsupporting

confidence: 91%

“…Study details and clinical characteristics have been reported. 16 All patients had positive results for dengue-specific IgM, as determined by enzyme-linked immunosorbent assay (Focus Technologies, Chanhassen, MN). The Ethics Committee of Diponegoro University in Indonesia approved the study.…”

Section: Methodsmentioning

confidence: 99%

Imbalance of Angiopoietin-1 and Angiopoetin-2 in Severe Dengue and Relationship with Thrombocytopenia, Endothelial Activation, and Vascular Stability

Michels¹,

Ven²,

Djamiatun³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…One pediatric study by Sardà Sanchez et al [ 8 ] showed that ProADM could predict simple pneumonia versus pneumonia with complications (2.32 vs. 1.18 nmol/L, p = 0.014) or pleural effusion (2.94 vs. 1.14, p < 0.001), but only fifty patients were included in this study, including ten with complications, of which seven with pleural effusions. Another pediatric study by Michels et al [ 7 ] concluded that ProADM also predicts capillary damage, leakage and risk of shock in hemorrhagic dengue and dengue shock, showing that these lesions similar to sepsis can be predicted by this marker in non-bacterial sepsis-like syndromes.…”

Section: Discussionmentioning

confidence: 99%

“…These novel biomarkers seem useful in predicting severity and complications in severe pneumonia in adults [ 4 – 6 ], but very few studies have explored the predictive value of these markers in children [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Proadrenomedullin and copeptin in pediatric pneumonia: a prospective diagnostic accuracy study

et al. 2015

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BackgroundCommunity-acquired-pneumonia is the leading cause of child mortality worldwide. Very few studies have explored the predictive value of Proadrenomedullin and Copeptin in pediatric severe pneumonia and bacteremia.MethodsProadrenomedullin and Copeptin were assessed as predictors for complicated community-acquired pneumonia (bacteremia, empyema) in 88 children aged 0 to 16 years presenting to the pediatric emergency department, using B.R.A.H.M.S. Kryptor Compact pro-ADM and Copeptin with the TRACE technology (time-resolved amplified cryptase emission). STARD standard reporting was used.ResultsA complicated community-acquired pneumonia was found in 11 out of 88 children (12.5 %). Proadrenomedullin median values increased more than twofold, in complicated vs. uncomplicated (0.18 vs. 0.08 nmol/L, p = 0.039), and fivefold in bacteremic vs. non-bacteremic pneumonia (0.40 vs. 0.08 nmol/L, p = 0.02). Proadrenomedullin > 0.16 nmol/L showed 100 % sensitivity (95 % CI 39.8 – 100.0) and 70 % (95 % CI 58.7 – 79.7) specificity for bacteremia. Copeptin showed no added-value.ConclusionsProadrenomedullin seems a reliable and available predictor for complicated CAP, and could therefore help the physician with the decision to hospitalize, and choose the antibiotics administration route. Larger studies are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1095-5) contains supplementary material, which is available to authorized users.

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“…Endothelial cells play a crucial role in the pathophysiology of plasma leakage in dengue viral infection. 6 Angiopoietin-1 (Ang-1) and Ang-2 are known to bind Tie-2 receptors in endothelial cell. The binding of Ang-2 to Tie receptor could increased angiogenesis induced by Vascular Endothelial Growth Factor (VEGF), induced endothelial cells apoptosis and finally potentiating with Tumor Necrosis Factor-α (TNF-α) in expressing surface adhesion molecules.…”

Section: Introductionmentioning

confidence: 99%

Serum Angiopoietin-2 as Marker of Plasma Leakage in Dengue Viral Infection

Rampengan¹,

Daud²,

Warouw³

et al. 2015

AJCEM

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Background. The immunopathology of DHF/DSS is yet completely understood. Angiopoietin-2 (Ang-2) produced by endothelial cell could promote vascular leakage by disrupting endothelial junction. Few studies reported the role of Ang-2 in dengue viral infection. Objective. To study the role of Ang-2 in promoting vascular leakage in dengue viral infection. Methods. Prospective cohort study conducted at Prof. Dr. R.D. Kandou, Pancaran Kasih and R.W. Mongonsidi General Hospitals in Manado, from March 2013 to October 2014. Children, aged 1-15 years old, with the diagnosis of dengue viral infection according to 1997 World Health Organization (WHO) criteria [Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), Dengue Shock Syndrome (DSS)],were recruited consecutively. Written informed consent was obtained from parents or legal guardian. Blood samples were obtained at the time of diagnosis and 48 hours after, evaluated for complete blood counts, albumin, NS-1, Ig M, Ig G anti-dengue, and Ang-2. Results. During the study period, there were 119 children with dengue viral infections (39 DF, 39 DHF, 41 DSS). Patient's characteristics: female predominance, age between 1.5-8.5 years old, well nourished, and mean albumin level were less than ≤3.5 gr% in the DHF and DSS group. Ang-2 level at admission were 2,486.21 pg/dl, 3,194.95 pg/dl and 4,005.32 pg/dl in DF, DHF and DSS group, respectively. Anova test analyses shows significant differences in serum Ang-2 level at admission between DF, DHF and DSS group (p<0.0001). Between those groups, DSS group had the highest level of Ang-2, followed with DHF and DF. Discussion. Mean albumin level were 3.88 gr%, 3.39 gr% and 2.63gr% in DF, DHF and DSS group, respectively. This results shows increasing plasma leakage with increasing severity of dengue viral infection. Increasing level of Ang-2 can promote blood vessels instability therefore causing increased vascular permeability and subsequent plasma leakage. In this study, we found significant elevation of serum Ang-2 in patiens with DSS compared to DHF and DF but the difference was not significant between DF and DHF group. Conclusions. Angiopoietin-2 contributes in transient systemic vascular leak in dengue viral infection.

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High plasma mid-regional pro-adrenomedullin levels in children with severe dengue virus infections

Cited by 22 publications

References 19 publications

Imbalance of Angiopoietin-1 and Angiopoetin-2 in Severe Dengue and Relationship with Thrombocytopenia, Endothelial Activation, and Vascular Stability

Imbalance of Angiopoietin-1 and Angiopoetin-2 in Severe Dengue and Relationship with Thrombocytopenia, Endothelial Activation, and Vascular Stability

Proadrenomedullin and copeptin in pediatric pneumonia: a prospective diagnostic accuracy study

Serum Angiopoietin-2 as Marker of Plasma Leakage in Dengue Viral Infection

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