title: Factor V Leiden mutation does not affect coagulopathy or outcome in lethal H1N1 influenza.
abstract: Influenza A is a major cause of mortality. Knowledge on coagulation activation in influenza infection is limited. The factor V Leiden (FVL) mutation is possibly subject to positive selection pressure. It is unknown whether this mutation impacts on the outcome of severe influenza. In the present study, the effect of lethal influenza on pulmonary and systemic coagulation activation and whether or not FVL mutation alters coagulation activation in and the course of lethal influenza, was determined. Wild-type mice, and mice heterozygous or homozygous for FVL were infected intranasally with a lethal dose of H1N1 (haemagglutinin 1 and neuraminidase 1) influenza A. Mice were sacrificed after 48 or 96 h for determination of coagulation activation, histopathology, pulmonary inflammatory parameters and viral load, or were observed in a survival study. Extensive local and systemic coagulation activation during lethal influenza was demonstrated by increased lung and plasma levels of thrombin-antithrombin complexes and fibrin degradation products, and by pulmonary fibrin deposition. FVL mutation did not influence the procoagulant response, lung histopathology or survival. FVL mice demonstrated elevated viral loads 48 h after infection. In conclusion, coagulation is activated locally and systemically during lethal murine influenza A infection. The FVL mutation does not influence coagulation activation, lung inflammation or survival in lethal influenza A.
authors.affiliation: Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands. m.schouten@amc.uva.nl
authors.forename: M
authors.initials: M
authors.lastname: Schouten
authors.forename: K F
authors.initials: KF
authors.lastname: van der Sluijs
authors.forename: J J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: C
authors.initials: C
authors.lastname: Van't Veer
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000032:analysis; D001778:Blood Coagulation Disorders / Q000235:genetics*; D001779:Blood Coagulation Factors / Q000032:analysis; D005165:Factor V / Q000235:genetics*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006579:Heterozygote; D006720:Homozygote; D053118:Influenza A Virus, H1N1 Subtype; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000097:blood* / Q000401:mortality*; D017354:Point Mutation; D012720:Severity of Illness Index; D013917:Thrombin / Q000032:analysis; D019562:Viral Load
chemical_list: D000991:Antithrombins; D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; C095381:factor V Leiden; D005165:Factor V; D013917:Thrombin