NDLI: Impact of the factor V Leiden mutation on the outcome of pneumococcal pneumonia: a controlled laboratory study

Content Provider	Springer Nature : BioMed Central
Author	Schouten, Marcel van't Veer, Cornelis Roelofs, Joris JTH Levi, Marcel van der Poll, Tom
Abstract	Introduction Streptococcus (S.) pneumoniae is the most common cause of community-acquired pneumonia. The factor V Leiden (FVL) mutation results in resistance of activated FV to inactivation by activated protein C and thereby in a prothrombotic phenotype. Human heterozygous FVL carriers have been reported to be relatively protected against sepsis-related mortality. We here determined the effect of the FVL mutation on coagulation, inflammation, bacterial outgrowth and outcome in murine pneumococcal pneumonia. Methods Wild-type mice and mice heterozygous or homozygous for the FVL mutation were infected intranasally with 2*106 colony forming units of viable S. pneumoniae. Mice were euthanized after 24 or 48 hours or observed in a survival study. In separate experiments mice were treated with ceftriaxone intraperitoneally 24 hours after infection and euthanized after 48 hours or observed in a survival study. Results The FVL mutation had no consistent effect on activation of coagulation in either the presence or absence of ceftriaxone therapy, as reflected by comparable lung and plasma levels of thrombin-antithrombin complexes and fibrin degradation products. Moreover, the FVL mutation had no effect on lung histopathology, neutrophil influx, cytokine and chemokine levels or bacterial outgrowth. Remarkably, homozygous FVL mice were strongly protected against death due to pneumococcal pneumonia when treated with ceftriaxone, which was associated with more pronounced FXIII depletion; this protective effect was not observed in the absence of antibiotic therapy. Conclusions Homozygosity for the FVL mutation protects against lethality due to pneumococcal pneumonia in mice treated with antibiotics.
Related Links	https://ccforum.biomedcentral.com/counter/pdf/10.1186/cc9213.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
ISSN	13648535
DOI	10.1186/cc9213
Journal	Critical Care
Issue Number	4
Volume Number	14
Language	English
Publisher	BioMed Central
Publisher Date	2010-08-03
Access Restriction	Open
Subject Keyword	Intensive Critical Care Medicine Emergency Medicine Severe Sepsis Factor Xiii Pneumococcal Pneumonia Factor Versus Leiden Fibrin Degradation Product
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine
Journal Impact Factor	8.8/2023
5-Year Journal Impact Factor	10.4/2023

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