Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13 英文参考文献.docVIP

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Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13 英文参考文献.doc

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Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13 英文参考文献

SevereDengueIsAssociatedwithConsumptionofvon WillebrandFactorandItsCleavingEnzymeADAMTS-13 KisDjamiatun1,AndreJ.A.M.vanderVen2,PhilipG.deGroot3,SultanaM.H.Faradz4,D.Hapsari5, WilM.V.Dolmans2,SilvieSebastian3,RobFijnheer3,QuirijndeMast2* 1Department of Parasitology, Faculty of Medicine, Diponegoro University, Semarang, Indonesia, 2Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 3Laboratory for Thrombosis and Haemostasis, Department of Clinical Chemistry and Haematology, University MedicalCentre,Utrecht,TheNetherlands,4DivisionofHumanGenetics,FacultyofMedicine,DiponegoroUniversity,Semarang,Indonesia,5DepartmentofPediatrics, FacultyofMedicine,DiponegoroUniversity,Semarang,Indonesia Abstract Background: Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activationwithexocytosisofWeibel-Paladebodies(WPBs)mayplayanetiologicalroleinthiscondition. MethodsandPrincipalFindings:Inacohortof73Indonesianchildrenwithdenguehemorrhagicfever(DHF),ofwhich30 with dengue shock syndrome (DSS), we measured plasma levels of the WPB constituents von Willebrand factor antigen (VWF:Ag),VWFpropeptideandosteoprotegerin(OPG),togetherwithactivitylevelsoftheVWF-cleavingenzymeADAMTS- 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-13activity.TheVWFactivationfactorwasalsosignificantlyhigherinDHF/DSSandhighestinchildrenwhodied. There were significant differences in the kinetics of the various WPB constituents: VWF propeptide and OPG levels decreasedtoward discharge,while VWF:Aglevelswerelowerthanexpectedat enrollmentwithplasma levelsincreasing towarddischarge.Moreover,VWFpropeptidelevelscorrelatedbetterwithmarkersofdiseaseseverity(plateletcount,liver enzymes,serumalbuminandpleuraleffusionindex)thanc