title: Hyperferritinaemia in dengue virus infected patients is associated with immune activation and coagulation disturbances.
abstract: BACKGROUND
  During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances.
  
  
  RESULTS
  Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile.
  
  
  CONCLUSIONS
  Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully.
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelia A M
authors.initials: CA
authors.lastname: van de Weg
authors.affiliation: Emergency Department and Department of Internal Medicine, Dr. Horacio E. Oduber Hospitaal, Oranjestad, Aruba.
authors.forename: Ralph M H G
authors.initials: RM
authors.lastname: Huits
authors.affiliation: Instituto de Medicina Tropical de São Paulo e Departamento de Moléstias Infecciosas e Parasitárias (LIM-52), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Cláudio S
authors.initials: CS
authors.lastname: Pannuti
authors.affiliation: Landslaboratorium, Oranjestad, Aruba.
authors.forename: Rosalba M
authors.initials: RM
authors.lastname: Brouns
authors.affiliation: Landslaboratorium, Oranjestad, Aruba.
authors.forename: Riemsdijk W A
authors.initials: RW
authors.lastname: van den Berg
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: van den Ham
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Byron E E
authors.initials: BE
authors.lastname: Martina
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Department of Experimental Internal Medicine, Radboud University, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Eric C M
authors.initials: EC
authors.lastname: van Gorp
authors.affiliation: Disciplina de Imunologia Clínica e Alergia (LIM-60), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000150:complications / Q000276:immunology*; D001938:Brazil; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D003715:Dengue / Q000097:blood* / Q000150:complications / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology; D004196:Disease Outbreaks; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D020382:Interleukin-18 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009426:Netherlands
chemical_list: D015415:Biomarkers; D016207:Cytokines; D020382:Interleukin-18; D005293:Ferritins