Thromb Haemost 2007; 97(04): 627-634
DOI: 10.1160/TH06-02-0094
Wound Healing and Inflammation/Infection
Schattauer GmbH

Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection

Darintr Sosothikul
1   Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
,
Panya Seksarn
1   Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
,
Sureeporn Pongsewalak
1   Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
,
Usa Thisyakorn
1   Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
,
Jeanne Lusher
2   Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 16. Februar 2006

Accepted after resubmission 23. Januar 2007

Publikationsdatum:
24. November 2017 (online)

Summary

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, vonWillebrand factor antigen (vWF:Ag),tissue factor (TF) and plasminogen activator inhibitor (PAI-1) were significantly elevated, while platelet counts andADAMTS 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.

 
  • References

  • 1 Halstead SB. Epidemiology of Dengue and Dengue Hemorhagic Fever. In: Dengue and Dengue Hemorrhagic Fever. New York: CAB international Press; 1997: 23-44.
  • 2 Dengue Hemorhagic Fever: Diagnosis, treatment, prevention and control. In. 2d ed. 1987. Geneva: World Health Organization; 12-47.
  • 3 Mitrakul C. Bleeding problem in dengue haemorrhagic fever: platelets and coagulation changes. Southeast Asian J Trop Med Public Health 1987; 18: 407-412.
  • 4 Srichaikul T, Nimmanitaya S, Artchararit N. et al. Fibrinogen metabolism and disseminated intravascular coagulation in dengue hemorrhagic fever. Am J Trop Med Hyg 1977; 26: 525-532.
  • 5 Srichaikul T, Nimmannitya S. Haematology in dengue and dengue haemorrhagic fever. Baillieres Best Pract Res Clin Haematol 2000; 13: 261-276.
  • 6 Krishnamurti C, Wahl LM, Alving BM. Stimulation of plasminogen activator inhibitor activity in human monocytes infected with dengue virus. Am J Trop Med Hyg 1989; 40: 102-107.
  • 7 Markoff LJ, Innis BL, Houghten R. et al. Development of cross-reactive antibodies to plasminogen during the immune response to dengue virus infection. J Infect Dis 1991; 164: 294-301.
  • 8 Bethell DB, Flobbe K, Cao XT. et al. Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever. J Infect Dis 1998; 177: 778-782.
  • 9 Suharti C, van Gorp EC, Setiati TE. et al. The role of cytokines in activation of coagulation and fibrinolysis in dengue shock syndrome. Thromb Haemost 2002; 87: 42-46.
  • 10 Green S, Vaughn DW, Kalayanarooj S. et al. Early immune activation in acute dengue illness is related to development of plasma leakage and disease severity. J Infect Dis 1999; 179: 755-762.
  • 11 Krishnamurti C, Kalayanarooj S, Cutting MA. et al. Mechanisms of hemorrhage in dengue without circulatory collapse. Am J Trop Med Hyg 2001; 65: 840-847.
  • 12 Buchanan GR, Adix L. Grading of hemorrhage in children with idiopathic thrombocytopenic purpura. J Pediatr 2002; 141: 683-688.
  • 13 Innis BL, Nisalak A, Nimmannitya S. et al. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg 1989; 40: 418-427.
  • 14 Lanciotti RS, Calisher CH, Gubler DJ. et al. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol 1992; 30: 545-551.
  • 15 Cejka J. Enzyme immunoassay for factor VIII-related antigen. Clin Chem 1982; 28: 1356-1358.
  • 16 Favaloro EJ, Grispo L, Exner T. et al. Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand's disease. Blood Coagul Fibrinolysis 1991; 2: 285-291.
  • 17 Ruggeri ZM, Zimmerman TS. Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325.
  • 18 Gerritsen HE, Turecek PL, Schwarz HP. et al. Assay of von Willebrand factor (vWF)-cleaving protease based on decreased collagen binding affinity of degraded vWF: a tool for the diagnosis of thrombotic thrombocytopenic purpura (TTP). Thromb Haemost 1999; 82: 1386-1389.
  • 19 Huang YH, Liu CC, Wang ST. et al. Activation of coagulation and fibrinolysis during dengue virus infection. J Med Virol 2001; 63: 247-251.
  • 20 van Gorp EC, Minnema MC, Suharti C. et al. Activation of coagulation factor XI, without detectable contact activation in dengue haemorrhagic fever. Br J Haematol 2001; 113: 94-99.
  • 21 Van Gorp EC, Setiati TE, Mairuhu AT. et al. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever. J Med Virol 2002; 67: 549-554.
  • 22 Wills BA, Oragui EE, Stephens AC. et al. Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome. Clin Infect Dis 2002; 35: 277-285.
  • 23 Carlos CC, Oishi K, Cinco MT. et al. Comparison of clinical features and hematologic abnormalities between dengue fever and dengue hemorrhagic fever among children in the Philippines. Am J Trop Med Hyg 2005; 73: 435-440.
  • 24 Basuki PS. A glance at the von Willebrand factor in dengue virus infection. Southeast Asian J Trop Med Public Health 2003; 34: 559-563.
  • 25 Tsai HM, Nagel RL, Hatcher VB. et al. Multimeric composition of endothelial cell-derived von Willebrand factor. Blood 1989; 73: 2074-2076.
  • 26 Ono T, Mimuro J, Madoiwa S. et al. Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood 2006; 107: 528-534.
  • 27 Srichaikul T, Punyagupta S, Nitiyanant P. et al. Disseminated intravascular coagulation in adult Dengue haemorrhagic fever: Report of three cases. Southeast Asian J Trop Med Public Health 1975; 6: 106-114.
  • 28 Gill JC, Wilson AD, Endres-Brooks J. et al. Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood 1986; 67: 758-761.
  • 29 Vincentelli A, Susen S, Le Tourneau T. et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349: 343-349.
  • 30 Moore JC, Hayward CP, Warkentin TE. et al. Decreased von Willebrand factor protease activity associated with thrombocytopenic disorders. Blood 2001; 98: 1842-1846.
  • 31 Esmon CT, Gu JM, Xu J. et al. Regulation and functions of the protein C anticoagulant pathway. Haematologica 1999; 84: 363-368.
  • 32 Esmon CT. Molecular events that control the protein C anticoagulant pathway. Thromb Haemost 1993; 70: 29-35.
  • 33 Ishii H, Uchiyama H, Kazama M. Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemost 1991; 65: 618-623.
  • 34 Anderson R, Wang S, Osiowy C. et al. Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes. J Virol 1997; 71: 4226-4232.
  • 35 Bunyaratvej A, Butthep P, Yoksan S. et al. Dengue viruses induce cell proliferation and morphological changes of endothelial cells. Southeast Asian J Trop Med Public Health 1997; 28 (Suppl. 03) Suppl 32-37.
  • 36 Nemerson Y. Tissue factor and hemostasis. Blood 1988; 71: 1-8.
  • 37 Mesters RM, Mannucci PM, Coppola R. et al. Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. Blood 1996; 88: 881-886.
  • 38 Suffredini AF, Harpel PC, Parrillo JE. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. N Engl J Med 1989; 320: 1165-1172.
  • 39 Powars D, Larsen R, Johnson J. et al. Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 1993; 17: 254-261.
  • 40 Vervloet MG, Thijs LG, Hack CE. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemost 1998; 24: 33-44.
  • 41 Watanabe R, Wada H, Watanabe Y. et al. Activity and antigen levels of thrombin-activatable fibrinolysis inhibitor in plasma of patients with disseminated intravascular coagulation. Thromb Res 2001; 104: 1-6.