Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection.
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.
Sosothikul
Darintr
D
Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Sor Kor Building, Bangkok, Bangkok, Thailand. dsosothikul@hotmail.com
Seksarn
Panya
P
Pongsewalak
Sureeporn
S
Thisyakorn
Usa
U
Lusher
Jeanne
J
D051722:ADAM Proteins / Q000097:blood; D000071120:ADAMTS13 Protein; D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D025901:Carboxypeptidase B2 / Q000097:blood; D002648:Child; D015331:Cohort Studies; D003715:Dengue / Q000097:blood* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010976:Platelet Count; D011379:Prognosis; D011446:Prospective Studies; D019595:Severe Dengue / Q000097:blood* / Q000378:metabolism; D012720:Severity of Illness Index; D018180:Thrombomodulin / Q000097:blood; D013925:Thromboplastin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism*
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D018180:Thrombomodulin; D014841:von Willebrand Factor; D013925:Thromboplastin; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human