title: Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study.
abstract: BACKGROUND
  Disturbance of the pro-coagulatant and anti-coagulant balance is associated with a poor outcome from critical illness. The objective of this study is to determine whether the Factor V Leiden (FVL) mutation is associated with susceptibility to or death from critical illness.
  
  
  METHODS
  A genetic association study involving four case cohorts comprising two Gram negative sepsis, one invasive pneumococcal disease and one intensive care unit cohort with a total of 1,249 patients. Controls were derived from a population-based cohort study (N = 8,147). DNA from patients and controls was genotyped for the FVL mutation.
  
  
  RESULTS
  When all patients were investigated together no significant difference in the frequency of FVL mutation was observed compared with controls (odds ratio (OR), 1.03; 95% confidence interval (CI), 0.83 to 1.29). However, when stratified among patients admitted to intensive care (N = 237), susceptibility and the likelihood of long-term death was influenced by the FVL mutation. In adjusted logistic regression analysis, FVL carriers had an increased risk of ICU admission compared to non-carriers (OR 1.62; 95% CI, 1.08 to 2.42). In adjusted Cox regression analysis, FVL carriers were at increased risk of long-term death compared to non-carriers (relative risk 1.78; 95% CI, 1.13 to 2.81). FVL carrier status did not predict either susceptibility to or outcome from Gram negative, Escherichia coli or Streptococcus pneumoniae sepsis.
  
  
  CONCLUSIONS
  Overall, the FVL mutation did not appear to increase the risk of admission due to severe invasive infections. Nevertheless, in the subgroup of patients admitted to intensive care an increased risk and a poorer long-term outcome for individuals with critical illness were observed for FVL mutation carriers.
authors.affiliation: Department of Infectious Diseases and Clinical Research Centre, Hvidovre University Hospital, Kettegaard Alle 30, Hvidovre, Denmark. tlb@dadlnet.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Benfield
authors.forename: Karen
authors.initials: K
authors.lastname: Ejrnaes
authors.forename: Klaus
authors.initials: K
authors.lastname: Juul
authors.forename: Christian
authors.initials: C
authors.lastname: Østergaard
authors.forename: Jannik
authors.initials: J
authors.lastname: Helweg-Larsen
authors.forename: Nina
authors.initials: N
authors.lastname: Weis
authors.forename: Lea
authors.initials: L
authors.lastname: Munthe-Fog
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.forename: Marianne Ring
authors.initials: MR
authors.lastname: Andersen
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjaerg-Hansen
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality; D003718:Denmark / Q000453:epidemiology; D005165:Factor V / Q000235:genetics* / Q000502:physiology*; D006090:Gram-Negative Bacteria / Q000276:immunology; D006801:Humans; D017063:Outcome Assessment, Health Care; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods; D018805:Sepsis / Q000401:mortality / Q000503:physiopathology
chemical_list: C095381:factor V Leiden; D005165:Factor V