title: Anticoagulation increases alveolar hemorrhage in mice infected with influenza A.
abstract: Influenza A virus infection is a common respiratory tract infection. Alveolar hemorrhage has been reported in patients with influenza pneumonia and in mice infected with influenza A. In this study, we investigated the effect of two anticoagulants on alveolar hemorrhage after influenza A virus (IAV) infection of wild-type mice. Wild-type mice were anticoagulated with either warfarin or the direct thrombin inhibitor dabigatran etexilate and then infected with a mouse-adapted influenza virus (A/Puerto Rico/8/34 H1N1). Alveolar hemorrhage was assessed by measuring hemoglobin levels in the bronchoalveolar lavage fluid (BALF). We also measured vascular permeability and viral genomes in the lung, as well as white blood cells, inflammatory mediators, and protein in BALF Survival and body weight were monitored for 14 days after influenza A infection. In infected mice receiving either warfarin or dabigatran etexilate we observed decreased activation of coagulation in the BALF and increased alveolar hemorrhage. Warfarin but not dabigatran etexilate increased vascular permeability and mortality of influenza A-infected mice. Anticoagulation did not affect levels of influenza A genomes, white blood cells, inflammatory mediators, or protein in the BALF Our study indicates that systemic anticoagulation increases alveolar hemorrhage in influenza A-infected mice.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Silvio
authors.initials: S
authors.lastname: Antoniak
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Gondouin
authors.affiliation: Department of Nutrition, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Neidich
authors.affiliation: Department of Nutrition, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Beck
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mickelson
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Dougald M
authors.initials: DM
authors.lastname: Monroe
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bastarache
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina nigel_mackman@med.unc.edu.
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects*; D002199:Capillary Permeability / Q000187:drug effects; D000069604:Dabigatran / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced* / Q000821:virology*; D007249:Inflammation / Q000821:virology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000150:complications*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000503:physiopathology / Q000821:virology*; D016019:Survival Analysis; D014859:Warfarin / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D000069604:Dabigatran
keywords: Alveolar hemorrhage; anticoagulation; influenza A virus infection; mouse model