title: Activation of coagulation and tissue fibrin deposition in experimental influenza in ferrets.
abstract: BACKGROUND
  Epidemiological studies relate influenza infection with vascular diseases like myocardial infarction. The hypothesis that influenza infection has procoagulant effects on humans has been investigated by experimental animal models. However, these studies often made use of animal models only susceptible to adapted influenza viruses (mouse adapted influenza strains) or remained inconclusive. Therefore, we decided to study the influence of infection with human influenza virus isolates on coagulation in the well-established ferret influenza model.
  
  
  RESULTS
  After infection with either a seasonal-, pandemic- or highly pathogenic avian influenza (HPAI-H5N1) virus strain infected animals showed alterations in hemostasis compared to the control animals. Specifically on day 4 post infection, a four second rise in both PT and aPTT was observed. D-dimer concentrations increased in all 3 influenza groups with the highest concentrations in the pandemic influenza group. Von Willebrand factor activity levels increased early in infection suggesting endothelial cell activation. Mean thrombin-antithrombin complex levels increased in both pandemic and HPAI-H5N1 virus infected ferrets. At tissue level, fibrin staining showed intracapillary fibrin deposition especially in HPAI-H5N1 virus infected ferrets.
  
  
  CONCLUSIONS
  This study showed hemostatic alterations both at the circulatory and at the tissue level upon infection with different influenza viruses in an animal model closely mimicking human influenza virus infection. Alterations largely correlated with the severity of the respective influenza virus infections.
authors.affiliation: Department of Viroscience laboratory, Erasmus MC, room ee1671, Rotterdam, CE 50 3015, The Netherlands. m.goeijenbier@erasmusmc.nl.
authors.forename: Marco
authors.initials: M
authors.lastname: Goeijenbier
authors.forename: Eric C M
authors.initials: EC
authors.lastname: van Gorp
authors.forename: Judith M A
authors.initials: JM
authors.lastname: Van den Brand
authors.forename: Koert
authors.initials: K
authors.lastname: Stittelaar
authors.forename: Kamran
authors.initials: K
authors.lastname: Bakhtiari
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.forename: Byron E E
authors.initials: BE
authors.lastname: Martina
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders; D004195:Disease Models, Animal; D005289:Ferrets; D005337:Fibrin / Q000032:analysis*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006651:Histocytochemistry; D008168:Lung / Q000473:pathology; D008297:Male; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000473:pathology*; D010314:Partial Thromboplastin Time; D013918:Thrombin Time; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014841:von Willebrand Factor; D005337:Fibrin