Source:http://linkedlifedata.com/resource/pubmed/id/12869495
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2003-10-21
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pubmed:abstractText |
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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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Factor V,
http://linkedlifedata.com/resource/pubmed/chemical/Protein C,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/factor V Leiden
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3085-92
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12869495-Aged,
pubmed-meshheading:12869495-Animals,
pubmed-meshheading:12869495-Biological Markers,
pubmed-meshheading:12869495-Blood Coagulation,
pubmed-meshheading:12869495-Endotoxemia,
pubmed-meshheading:12869495-Factor V,
pubmed-meshheading:12869495-Female,
pubmed-meshheading:12869495-Heterozygote,
pubmed-meshheading:12869495-Humans,
pubmed-meshheading:12869495-Inflammation,
pubmed-meshheading:12869495-Male,
pubmed-meshheading:12869495-Mice,
pubmed-meshheading:12869495-Mice, Mutant Strains,
pubmed-meshheading:12869495-Middle Aged,
pubmed-meshheading:12869495-Point Mutation,
pubmed-meshheading:12869495-Protein C,
pubmed-meshheading:12869495-Recombinant Proteins,
pubmed-meshheading:12869495-Retrospective Studies,
pubmed-meshheading:12869495-Sepsis,
pubmed-meshheading:12869495-Survival Rate,
pubmed-meshheading:12869495-Treatment Outcome
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pubmed:year |
2003
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pubmed:articleTitle |
Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia.
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pubmed:affiliation |
Blood Research Institute, Blood Center of Southeast Wisconsin and Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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