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 Kronborg; Marianne Ring Andersen; Anne Tybjaerg-Hansen; Børge G Nordestgaard; Peter Garred

doi:10.1186/cc8899

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

Department of Clinical Medicine

12 Citations (Scopus)

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 language	English
Journal	Critical Care (Online Edition)
Volume	14
Issue number	2
Pages (from-to)	R28
ISSN	1466-609X
DOIs	https://doi.org/10.1186/cc8899 https://doi.org/10.1186/cc8899
Publication status	Published - 5 Mar 2010

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Benfield, T., Ejrnæs, K., Juul, K., Ostergaard, C., Helweg-Larsen, J., Weis, N., Munthe-Fog, L., Kronborg, G., Andersen, M. R., Tybjærg-Hansen, A., Nordestgaard, B. G., Garred, P., Benfield, T., Ejrnaes, K., Juul, K., Andersen, C. Ø., Helweg-Larsen, J., Weis, N. M., Munthe-Fog, L., ... Garred, P. (2010). Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study. Critical Care (Online Edition), 14(2), R28. https://doi.org/10.1186/cc8899, https://doi.org/10.1186/cc8899

Benfield, T, Ejrnæs, K, Juul, K, Ostergaard, C, Helweg-Larsen, J, Weis, N, Munthe-Fog, L, Kronborg, G, Andersen, MR, Tybjærg-Hansen, A, Nordestgaard, BG, Garred, P, Benfield, T, Ejrnaes, K, Juul, K, Andersen, CØ, Helweg-Larsen, J, Weis, NM, Munthe-Fog, L, Kronborg, G, Andersen, MR, Tybjaerg-Hansen, A , Nordestgaard, BG & Garred, P 2010, 'Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study', Critical Care (Online Edition), vol. 14, no. 2, pp. R28. https://doi.org/10.1186/cc8899, https://doi.org/10.1186/cc8899

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

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.",

author = "Thomas Benfield and Karen Ejrn{\ae}s and Klaus Juul and Christian Ostergaard and Jannik Helweg-Larsen and Nina Weis and Lea Munthe-Fog and Gitte Kronborg and Andersen, {Marianne Ring} and Anne Tybj{\ae}rg-Hansen and Nordestgaard, {B{\o}rge G} and Peter Garred and Thomas Benfield and Karen Ejrnaes and Klaus Juul and Andersen, {Christian {\O}stergaard} and Jannik Helweg-Larsen and Weis, {Nina Margrethe} and Lea Munthe-Fog and Gitte Kronborg and Andersen, {Marianne Ring} and Anne Tybjaerg-Hansen and Nordestgaard, {B{\o}rge G} and Peter Garred",

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doi = "10.1186/cc8899",

language = "English",

volume = "14",

pages = "R28",

journal = "Critical Care",

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TY - JOUR

T1 - Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study

AU - Benfield, Thomas

AU - Ejrnæs, Karen

AU - Juul, Klaus

AU - Ostergaard, Christian

AU - Helweg-Larsen, Jannik

AU - Weis, Nina

AU - Munthe-Fog, Lea

AU - Kronborg, Gitte

AU - Andersen, Marianne Ring

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G

AU - Garred, Peter

AU - Benfield, Thomas

AU - Ejrnaes, Karen

AU - Juul, Klaus

AU - Andersen, Christian Østergaard

AU - Helweg-Larsen, Jannik

AU - Weis, Nina Margrethe

AU - Munthe-Fog, Lea

AU - Kronborg, Gitte

AU - Andersen, Marianne Ring

AU - Tybjaerg-Hansen, Anne

AU - Nordestgaard, Børge G

AU - Garred, Peter

PY - 2010/3/5

Y1 - 2010/3/5

N2 - 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.

AB - 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.

U2 - 10.1186/cc8899

DO - 10.1186/cc8899

M3 - Journal article

C2 - 20202226

SN - 1364-8535

VL - 14

SP - R28

JO - Critical Care

JF - Critical Care

IS - 2

ER -

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

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