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Dengue virus causes a febrile illness: Dengue fever (DF), and less frequently a life-threatening illness: Dengue hemorrhagic fever (DHF). Although severe bleeding remains a major cause of death in DHF, the pathogenesis of bleeding is poorly understood. This prospective cohort study was designed to determine the extent of activation of endothelial cells and the hemostatic system in correlation with clinical severity, and also to detect the best prognostic factor(s) for DHF. Endothelial cell activation, coagulation, anticoagulant and fibrinolysis parameters were measured in 42 children with Dengue infections (20 with DF and 22 with DHF) during three phases of illness. In DHF patients, during the febrile phase, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and plasminogen activator inhibitor (PAI-1) were significantly elevated, while platelet counts and ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin repeats) were significantly low compared to DF patients. During the toxic phase, soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA) and PAI-1 were also significantly increased, while ADAMTS 13 and thrombin activatable fibrinolysis inhibitor (TAFIa) were significantly low compared to DF patients. Abnormal vWF multimers were seen only in DHF patients. For endothelial cell injury and release of procoagulant components, activation of the coagulation cascade with thrombin generation, increased antifibrinolytic factors and consumption of natural anticoagulants, each appeared to play an important role in the development of hemorrhage in Dengue patients. Using logistic regression analysis, we found plasma VWF:Ag to be the best indicator of progression to DHF.
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PMID:Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection. 1739 26

Dengue virus (DV) causes a non-specific febrile illness known as Dengue fever (DF), and a severe life-threatening illness, Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). Hemostatic changes induced by this virus involve three main factors: thrombocytopenia, endothelial cell damage, and significant abnormalities of the coagulation and fibrinolysis systems. The pathogenesis of bleeding in DV infections remains unknown. In this article, we focused on the DV activating endothelial cells and altering the parameters of hemostasis system. The expression of hemostasis-related factors, Thrombomodulin, TF, TFPI, t-PA, and PAI-1, in DV-infected cells were determined by RT-PCR. Flow cytometry analysis and immunofluorescence staining confirmed that the expression levels of TM in the DV-infected HMEC-1 and THP-1 cells were increased. In addition, the purified recombinant domain III of the envelope glycoprotein of DV (EIII) could induce the expression of TM in the HMEC-1 cells and THP-1 cells. The TM expression induced by DV or EIII in the endothelial cells and monocytic cells suggests that the EIII of DV plays an important role in the pathogenesis of DHF/DSS.
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PMID:The envelope glycoprotein domain III of Dengue virus type 2 induced the expression of anticoagulant molecules in endothelial cells. 2052 54

Dengue hemorrhagic fever (DHF) is a more severe manifestation of dengue virus infection. Patients with DHF exhibit abnormal hematological indices, including high hematocrit, low white blood cells, low neutrophils, high lymphocytes, increased atypical lymphocytes, low platelets, slightly prolonged activated partial thromboplastin time, prothrombin time, and thrombin time. Abnormal platelet functions manifest as impaired platelet aggregation to ADP, and concurrent increases in plasma thromboglobulin and platelet factor 4 levels are also seen. Variable reductions in the activities of coagulation factors including prothrombin, V, VII, VIII, IX, and X may be present. The plasma level of antithrombin is typically normal, but protein C and protein S are modestly reduced. Within the fibrinolytic system, slightly increased levels of tissue-plasminogen activator accompanied by slightly increased plasminogen activator inhibitor-1 and decreased thrombin activatable fibrinolysis inhibitor have been demonstrated. These derangements are prominent in patients with DHF grades III and IV, collectively known as dengue shock syndrome. Moreover, patients with excessive depletion of intravascular volume from plasma leakage and/or massive bleeding from endothelial dysfunction, thrombocytopenia, platelet dysfunction, and coagulopathy may exhibit shock, prolonged shock and repeated shock. DIC is also commonly found in these complicated patients. However, most patients recover spontaneously with normalization of abnormal laboratory profiles during the convalescent stage or within one to two weeks after defervescence.
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PMID:Hemostatic derangement in dengue hemorrhagic fever. 2412 Feb 37