title: Evaluation of the host response to endotoxemia of FVIII and FIX deficient mice.
abstract: For several years, coagulation has been implicated in the pathogenesis of sepsis. However, results from clinical trials with natural anticoagulants, as well as studies with knock-out mice for specific coagulation factors yielded conflicting results on the role of coagulation in the pathogenesis of sepsis. The aim of this study was to evaluate the impact of severe The factor VIII:C (FVIII:C) and factor IX:C (FIX:C) deficiency on a lipopolysaccharide (LPS)-induced murine model of sepsis. FVIII:C and FIX:C deficient mice, and their haemostatic normal littermate controls were challenged with LPS, and several parameters of the host response were evaluated: seven-day survival experiments were performed using two dose levels of LPS; biochemical and histological markers of tissue damage, coagulation parameters, and pro-inflammatory cytokines were evaluated at baseline and after 3 h and 6 h after an injection of LPS. Severe FVIII and FIX deficiency were compatible with normal survival in experimental sepsis. In addition, LPS-induced tissue damage and coagulation activation were similar in FVIII or FIX deficient mice compared to their respective controls. A lower release of pro-inflammatory cytokines was observed in FIX but not in FVIII deficient mice. Severe FIX or FVIII deficiency does not protect mice from mortality or from tissue damage in the endotoxemia model, supporting the hypothesis that FVIII and FIX are not critical to the pathogenesis of experimental sepsis.
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
authors.forename: S M C
authors.initials: SM
authors.lastname: Vancine
authors.forename: S K
authors.initials: SK
authors.lastname: Picoli-Quaino
authors.forename: D S P
authors.initials: DS
authors.lastname: Costa
authors.forename: S A L
authors.initials: SA
authors.lastname: Montalvao
authors.forename: M C
authors.initials: MC
authors.lastname: Ozelo
authors.forename: J M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
authors.forename: E V
authors.initials: EV
authors.lastname: de Paula
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001777:Blood Coagulation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism*; D005340:Fibrinogen / Q000032:analysis; D006467:Hemophilia A / Q000378:metabolism* / Q000401:mortality; D002836:Hemophilia B / Q000378:metabolism* / Q000401:mortality; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; D005340:Fibrinogen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase