Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study.
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.
Benfield
Thomas
T
Department of Infectious Diseases and Clinical Research Centre, Hvidovre University Hospital, Kettegaard Alle 30, Hvidovre, Denmark. tlb@dadlnet.dk
Ejrnaes
Karen
K
Juul
Klaus
K
Østergaard
Christian
C
Helweg-Larsen
Jannik
J
Weis
Nina
N
Munthe-Fog
Lea
L
Kronborg
Gitte
G
Andersen
Marianne Ring
MR
Tybjaerg-Hansen
Anne
A
Nordestgaard
Børge G
BG
Garred
Peter
P
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
C095381:factor V Leiden; D005165:Factor V