Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia.
Blood
; 102(9): 3085-92, 2003 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-12869495
ABSTRACT
Sepsis is associated with systemic inflammation, coagulopathy, and disrupted protein C (PC) pathway function. The effect of prothrombotic polymorphism, factor V Leiden (Arg506Gln; FV Leiden), was examined in a large clinical trial (PROWESS) of severe sepsis and a mouse endotoxemia model. In PROWESS, 4.1% (n = 65) of patients were heterozygous FV Leiden (VL+/-) carriers. The 28-day mortality was lower in VL+/- (13.9%) than in non-FV Leiden (VL-/-; 27.9%) patients (P =.013). The mortality benefit of recombinant human activated PC (rhAPC) treatment was similar in VL+/- (placebo, 15.6%; rhAPC,12.1%) and VL-/- patients (placebo, 31.0%; rhAPC, 24.7%; interaction P =.981). VL+/- status did not appear to influence baseline biomarkers of coagulopathy and inflammation or disease severity, with the exception that vasopressor usage was less in VL+/- patients (46.2% versus 63.0%; P =.009). In a median lethal dose (40 mg/kg) endotoxin mouse model, VL+/- mice had lower mortality than wild-type mice (19% versus 57%; P =.008), whereas the mortality of homozygous (VL+/+) mice was almost identical to that of wild-type mice (65% versus 57%; P =.76). The findings suggest that FV Leiden constitutes a rare example of a balanced gene polymorphism that maintains the FV Leiden mutation in the general gene pool due to a survival advantage of VL+/- in severe sepsis.
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Base de dados:
MEDLINE
Assunto principal:
Fator V
/
Sepse
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Endotoxemia
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
/
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article