Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study

Thomas Benfield, Karen Ejrnæs, Klaus Juul, Christian Ostergaard, Jannik Helweg-Larsen, Nina Weis, Lea Munthe-Fog, Gitte Kronborg, Marianne Ring Andersen, Anne Tybjærg-Hansen, Børge G Nordestgaard, Peter Garred, Thomas Benfield, Karen Ejrnaes, Klaus Juul, Christian Østergaard Andersen, Jannik Helweg-Larsen, Nina Margrethe Weis, Lea Munthe-Fog, Gitte KronborgMarianne Ring Andersen, Anne Tybjaerg-Hansen, Børge G Nordestgaard, Peter Garred

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Abstract

ABSTRACT: INTRODUCTION: 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.
Original languageEnglish
JournalCritical Care (Online Edition)
Volume14
Issue number2
Pages (from-to)R28
ISSN1466-609X
DOIs
Publication statusPublished - 1 Jan 2010

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