Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-10-21
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3085-92
pubmed:dateRevised
2007-11-14
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
pubmed:year
2003
pubmed:articleTitle
Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia.
pubmed:affiliation
Blood Research Institute, Blood Center of Southeast Wisconsin and Medical College of Wisconsin, Milwaukee, WI 53226, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't