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

Contains fulltext : 108223.pdf (publisher's version ) (Open Access)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

Patient characteristics and baseline data for non-severe and severe dengue patients.

<p>Patient characteristics and baseline data for non-severe and severe dengue patients.</p

Hematocrit values in dengue patients with and without subclinical plasma leakage detected by handheld ultrasonography.

<p>(A) Absolute hematocrit values (%) (Normal maximum hematocrit value 50% and 44% for men and women, respectively) related to the presence or absence of plasma leakage detected by handheld ultrasonography on the day of enrollment. (B) Changes in hematocrit (%) related to the presence or absence of plasma leakage during the follow up of adult Indonesian dengue patients. Plasma leakage was detected in the form of ascites or pleural effusion by daily handheld ultrasonography at the bedside performed by a clinician and by conventional ultrasonography. The black dots indicate patients who developed severe dengue characterized by shock. The horizontal continuous lines represent median values. The horizontal interrupted line represents the reference value for hematocrit change (normally <20% change) P-values were determined by unpaired t-test for hematocrit values and by Mann Whitney U test for hematocrit changes. * p value<0.05; ** p value<0.01.</p

Ultrasonography findings showing presence or absence of ascites in dengue patients.

<p>Handheld ultrasonography performed at the bedside with the patient in supine position during examination. (A) Normal hepatic-renal area. (B) Minimal ascites in hepato-renal area (arrow). (C) Normal spleno-renal area. (D) Ascites in spleno-renal area (arrow). Abbreviations: L: liver; K: kidney, RLL: right lower lobe of lung; LLL: left lower lobe of lung; S: Spleen.</p

Criteria for severe dengue according to World Health Organization guidelines 1997 and 2009.

<p>Criteria for severe dengue according to World Health Organization guidelines 1997 and 2009.</p

Ultrasonography findings showing a normal and thickened gallbladder wall in dengue patients.

<p>Handheld ultrasonography performed at the bedside with the patient in supine position during examination. (A) normal gallbladder wall (<0.30 cm) (B) and thickened gallbladder wall. The gall bladder wall is thickened with 0.90 cm and has a subserosal fluid layer, giving the gallbladder wall a multiple layer aspect. Abbreviations: L: liver; GB: gallbladder lumen.</p

Ultrasonography findings of plasma leakage and hemoconcentration in non-severe and severe dengue patients.

<p>Ultrasonography findings of plasma leakage and hemoconcentration in non-severe and severe dengue patients.</p