Dataset Information

Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13.

ABSTRACT:

Background

Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs) may play an etiological role in this condition.

Methods and principal findings

In a cohort of 73 Indonesian children with dengue hemorrhagic fever (DHF), of which 30 with dengue shock syndrome (DSS), we measured plasma levels of the WPB constituents von Willebrand factor antigen (VWF:Ag), VWF propeptide and osteoprotegerin (OPG), together with activity levels of the VWF-cleaving enzyme ADAMTS-13 and the amount of VWF in a platelet binding conformation (VWF activation factor). Compared with healthy controls (n?=?17), children with DHF/DSS had significantly higher levels of VWF:Ag, VWF propeptide and OPG and decreased ADAMTS-13 activity. The VWF activation factor was also significantly higher in DHF/DSS and highest in children who died. There were significant differences in the kinetics of the various WPB constituents: VWF propeptide and OPG levels decreased toward discharge, while VWF:Ag levels were lower than expected at enrollment with plasma levels increasing toward discharge. Moreover, VWF propeptide levels correlated better with markers of disease severity (platelet count, liver enzymes, serum albumin and pleural effusion index) than corresponding VWF levels. Together, these findings suggest that there is consumption of VWF in DHF/DSS. In 4 out of 15 selected children with low ADAMTS-13 levels on admission, we found a remarkable reduction in the large and intermediate VWF multimers in the discharge blood samples, consistent with an acquired von Willebrand disease.

Conclusion

These findings suggest that severe dengue is associated with exocytosis of WPBs with increased circulating levels of VWF:Ag, VWF propeptide and OPG. High circulating levels of VWF in its active conformation, together with low ADAMTS-13 activity levels, are likely to contribute to the thrombocytopenia and complications of dengue. During the convalescence phase, qualitative defects in VWF with loss of larger VWF multimers may develop.

SUBMITTER: Djamiatun K

PROVIDER: S-EPMC3341341 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13.

Djamiatun Kis K van der Ven Andre J A M AJ de Groot Philip G PG Faradz Sultana M H SM Hapsari D D Dolmans Wil M V WM Sebastian Silvie S Fijnheer Rob R de Mast Quirijn Q

PLoS neglected tropical diseases 20120501 5

<h4>Background</h4>Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs) may play an etiological role in this condition.<h4>Methods and principal findings</h4>In a cohort of 73 Indonesian children with dengue hemorrhagic fever (DHF), of which 30 with dengue shock syndrome (DSS), we measured plasma levels of the WPB constituents von Willebrand factor antigen (VWF:Ag), VWF propeptide and oste ...[more]

PMID: 22563509

Similar Datasets

Project description:Backgroundvon Willebrand factor (VWF) multimers are cleaved by A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) into less active fragments. Thrombospondin 1 (TSP-1) competes with VWF's cleavage site, protecting it from degradation. Low ADAMTS-13 and high VWF have been associated with cardiovascular disease and atrial fibrillation (AF).ObjectivesWe aimed to investigate whether VWF, ADAMTS-13, and TSP-1 are associated with clinical outcome.MethodsElderly patients with a recent myocardial infarction (MI) (n = 1027) were followed for 2 years. Blood was collected 2 to 8 weeks after the MI for ADAMTS-13, VWF, and TSP-1 measures. The primary endpoints (major adverse cardiovascular events; n = 210) included the first event of MI, stroke, heart failure hospitalization, coronary revascularization, and all-cause death. Total mortality was also registered (n = 56). The secondary endpoint was new-onset AF (n = 43).ResultsConcentrations of VWF, ADAMTS-13, and TSP-1 did not intercorrelate. The risk of major adverse cardiovascular events was altered in patients with VWF ≥ median (hazard ratio [HR], 1.4; 95% CI, 1.0-1.8; P = .03) and ADAMTS-13 ≥ median (HR, 0.7; 95% CI, 0.5-0.9; P = .02); however, it was not significant in adjusted models. VWF and ADAMTS-13 were significantly associated with total mortality, with a HR of 2.7 (95% CI, 1.6-4.6; P < .001) for VWF (Q4 vs. Q1-Q3) and HR of 0.3 (95% CI, 0.2-0.5; P < .001) for ADAMTS-13 (Q2-4 vs. Q1). The associations persisted in multivariable analysis, but the significance disappeared for VWF after correcting for high-sensitivity C-reactive protein. The risk of new-onset AF was lower in patients with VWF ≥ median (HR, 0.5; 95% CI, 0.3-1.0; P = .04]), and this was still significant after adjustments.ConclusionAlthough low ADAMTS-13 predicted death, the cardiovascular risk associated with VWF and ADAMTS-13 was weaker than previously reported. Low VWF is associated with new-onset AF and needs further research.

Dataset Information

Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13.

Background

Methods and principal findings

Conclusion

Publications

Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13.

Similar Datasets

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