title: Disseminated intravascular coagulation in a novel porcine model of severe Staphylococcus aureus sepsis fulfills human clinical criteria.
abstract: Sepsis is a common and often fatal complication in human patients in intensive care units. Relevant and well characterized animal models of sepsis may provide valuable information on pathophysiological mechanisms and be a mean of testing new therapeutic strategies. Large animal models of Staphylococcus aureus sepsis are rare, even though S. aureus increasingly affects human patients. Sepsis changes the haemostatic balance and leads to endothelial cell (EC) activation, coagulopathy and, in severe cases, disseminated intravascular coagulation (DIC). The aim of this study was to characterize the haemostatic and vascular alterations in a novel porcine model of severe S. aureus sepsis, investigating whether the changes fulfill the human clinical criteria for DIC. Five pigs were inoculated intravenously with S. aureus and two control animals were sham-inoculated. Blood samples were collected for thromboelastography (TEG) and assessment of plasma-based haemostatic parameters. Tissue was collected for histopathology and reverse transcriptase quantitative real-time polymerase chain reaction for measurement of mRNA encoding EC markers. All infected animals developed DIC; including procoagulant activation represented by hypercoagulable TEG profiles and prolonged clotting time. Histologically, numerous pulmonary thrombi were present in one pig. Inhibitor consumption was represented by decreasing antithrombin levels in infected pigs. Hyaline globules were found in three infected pigs, confirming fibrinolytic activation. EC activation was identified by expression of von Willebrand factor in small vessels together with elevated mRNA encoding activated EC markers. Severe haemostatic and vascular changes fulfilling the human criteria for DIC were therefore seen in all infected pigs. A tendency towards uncompensated DIC was seen in two animals.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Pathology and Wildlife Disease, National Veterinary Institute, Sweden. Electronic address: elisabethsoerensen@gmail.com.
authors.forename: K E
authors.initials: KE
authors.lastname: Soerensen
authors.forename: H G
authors.initials: HG
authors.lastname: Olsen
authors.forename: K
authors.initials: K
authors.lastname: Skovgaard
authors.forename: B
authors.initials: B
authors.lastname: Wiinberg
authors.forename: O L
authors.initials: OL
authors.lastname: Nielsen
authors.forename: P S
authors.initials: PS
authors.lastname: Leifsson
authors.forename: H E
authors.initials: HE
authors.lastname: Jensen
authors.forename: A T
authors.initials: AT
authors.lastname: Kristensen
authors.forename: T M
authors.initials: TM
authors.lastname: Iburg
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D018805:Sepsis; D013203:Staphylococcal Infections / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013211:Staphylococcus aureus; D013552:Swine
keywords: DIC; Staphylococcus aureus; porcine model; sepsis