severe dengue is associated with consumption of von willebrand factor and its cleaving enzyme adamts-13严重的登革热与消费有关的血管性血友病因子及其酶adamts-13裂开.pdfVIP

Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13 1 2 3 4 5 Kis Djamiatun , Andre J. A. M. van der Ven , Philip G. de Groot , Sultana M. H. Faradz , D. Hapsari , 2 3 3 2 Wil M. V. Dolmans , Silvie Sebastian , Rob Fijnheer , Quirijn de Mast * 1 Department of Parasitology, Faculty of Medicine, Diponegoro University, Semarang, Indonesia, 2 Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 3 Laboratory for Thrombosis and Haemostasis, Department of Clinical Chemistry and Haematology, University Medical Centre, Utrecht, The Netherlands, 4 Division of Human Genetics, Faculty of Medicine, Diponegoro University, Semarang, Indonesia, 5 Department of Pediatrics, Faculty of Medicine, Diponegoro University, Semarang, Indonesia 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 level