thromboplastin and Dengue

Tissue Factor (TF) is the initiator of coagulation and Tissue Factor Inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Circulating levels of TF and TFPI were quantified in dengue patients and the relationships with disease severity and infecting serotype analysed. A significant decrease in TF and TPFI plasma levels was observed in mild DF patients compared with severe dengue. Furthermore, both factors were associated with haemorrhagic manifestations. Finally, TF levels were significantly increased in DENV-1/2 infected patients as compared with DENV-4. These findings suggest that activation of TF-pathway is an important component of DENV -related coagulation disorders.

Topics: Adult; Dengue; Dengue Virus; Female; Humans; Lipoproteins; Male; Middle Aged; Serogroup; Severity of Illness Index; Thromboplastin; Young Adult

Topics: Case-Control Studies; Dengue; Humans; Monocytes; Thromboplastin

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.

Topics: ADAM Proteins; ADAMTS13 Protein; Adolescent; Biomarkers; Blood Coagulation; Carboxypeptidase B2; Child; Cohort Studies; Dengue; Endothelial Cells; Fibrinolysis; Humans; Logistic Models; Odds Ratio; Plasminogen Activator Inhibitor 1; Platelet Count; Prognosis; Prospective Studies; Severe Dengue; Severity of Illness Index; Thrombomodulin; Thromboplastin; Tissue Plasminogen Activator; von Willebrand Factor

Dengue virus infection can induce mild dengue fever (DF) or severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in human. The pathogenesis of hemorrhage in dengue virus infection is not fully understood. Since hemostasis depends on the balance between coagulation and fibrinolysis, alternation of some coagulation parameters (platelet count and activated partial thromoboplastin time, APTT) as well as fibrinolytic parameters (tissue plasminogen activator, tPA and plasminogen activator inhibitor-1, PAI-1) were compared in 8 DHF/DSS and 17 DF patients. Patients showed thrombocytopenia, APTT prolongation, and tPA increase in the acute stage of disease, indicating activation of coagulation and fibrinolysis. The activation of coagulation and fibrinolysis in DHF/DSS patients was much more severe than DF patients. In the convalescent stage, a rise of PAI-1 level and platelet count with concomitant decline of tPA level and APTT returned to normal in both DHF/DSS and DF patients. Therefore, the activation of coagulation and fibrinolysis during the acute stage of dengue virus infection is offset by the increase of platelet and PAI-1 during convalescent stage. Taken together, these results suggest that the degree of coagulation and fibrinolysis activation induced by dengue virus infection is associated with the disease severity.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Coagulation; Child; Child, Preschool; Dengue; Female; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Platelet Count; Severe Dengue; Thromboplastin; Tissue Plasminogen Activator

In an attempt to reveal certain aspects of the pathogenesis of the bleeding disorder in dengue hemorrhagic fever, hemostatic and platelet kinetic studies were carried out in 61 children with this disease. As has been shown by others, thrombocytopenia and hypofibrinogenemia were the two most prominent hemostatic defects constantly discovered. Increased intravascular clotting seemed to be one responsible factor, though not an outstanding one. This was evidenced by mildly and variably low factors II, V, VII, VIII, IX, X, and XII, and by mild to moderate increase of fibrin degradation products as well as low platelet counts and fibrinogen. In 11 cases platelet kinetic study revealed increased destruction as a main cause for the thrombocytopenia, most probably due to the underlying immunologic mechanism, i.e., via the immune complexes formed. Another factor was platelet dysfunction--the release of adenosine diphosphate.

Topics: Adenosine Diphosphate; Blood Cell Count; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Child; Dengue; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hematocrit; Humans; Prothrombin Time; Thrombocytopenia; Thromboplastin