Document Detail


Evidence for endotoxin contamination in plastic Na+-heparin blood collection tube lots.
MedLine Citation:
PMID:  20663962     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Biomarker assays are often conducted on whole blood samples in the course of drug development studies. Because bacterial lipopolysaccharide (LPS) (endotoxin) contamination is known to cause spontaneous cytokine production by monocytes, contamination of blood collection tubes may interfere with biomarker assay results. METHODS: Whole blood from healthy donors was collected into plastic or glass sodium (Na(+))-heparin Vacutainer() blood collection tubes and heparinized syringes. Samples were analyzed for phosphoprotein response, cytokine production, and RNA expression. Tubes were tested for endotoxin contamination by use of the limulus amoebocyte lysate assay. RESULTS: Results of phospho-flow cytometry, branched DNA (bDNA), and ELISA assays indicated that a specific lot (#5339582) of plastic Na(+)-heparin Vacutainer tubes was highly contaminated with an endotoxinlike substance, and contamination was confirmed by the limulus amoebocyte lysate assay. Analysis of multiple-analyte panels revealed that analytes whose changed expression was predictive of LPS stimulation were increased when whole blood was incubated in contaminated tubes for 6 or 18 h. Two additional lots of plastic tubes tested had detectable amounts of endotoxin sufficient to strongly alter phospho-flow cytometry analyses, as determined by the fold change in phosphorylation of p38 mitogen-activated protein kinase in response to tumor necrosis factor alpha and LPS. In contrast, 3 lots of glass tubes had substantially lower levels of spontaneous blood activation. CONCLUSIONS: Endotoxin contamination associated with tubes from 3 lots of a particular type of plastic Na(+)-heparin Vacutainer tube dramatically affected biomarker assay measurements. Prescreening these tubes is suggested before their use in clinical sample analysis.
Authors:
Kathryn J Newhall; Geoffrey S Diemer; Natalia Leshinsky; Keith Kerkof; Hilary T Chute; Chris B Russell; William Rees; Andrew A Welcher; Scott D Patterson; Gary D Means
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-27
Journal Detail:
Title:  Clinical chemistry     Volume:  56     ISSN:  1530-8561     ISO Abbreviation:  Clin. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2010-09-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421549     Medline TA:  Clin Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1483-91     Citation Subset:  IM    
Affiliation:
Amgen Molecular Sciences, Amgen, Seattle, WA, USA. knewhall@amgen.com
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MeSH Terms
Descriptor/Qualifier:
Anticoagulants*
Biological Markers / blood
Blood Specimen Collection / instrumentation*
C-Reactive Protein / biosynthesis,  genetics
Chemokine CCL2 / blood,  genetics
Chemokine CCL7 / blood,  genetics
Endotoxins / analysis*
Enzyme-Linked Immunosorbent Assay
Equipment Contamination*
Flow Cytometry
Heparin*
Humans
Interleukin-1beta / blood
Interleukin-6 / blood,  genetics
Lipopolysaccharides / pharmacology
Phosphorylation
Plastics
RNA, Messenger / blood
Serum Amyloid P-Component / biosynthesis,  genetics
Time Factors
Tumor Necrosis Factor-alpha / biosynthesis,  pharmacology
p38 Mitogen-Activated Protein Kinases / blood
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Biological Markers; 0/Chemokine CCL2; 0/Chemokine CCL7; 0/Endotoxins; 0/Interleukin-1beta; 0/Interleukin-6; 0/Lipopolysaccharides; 0/Plastics; 0/RNA, Messenger; 0/Serum Amyloid P-Component; 0/Tumor Necrosis Factor-alpha; 148591-49-5/PTX3 protein; 9005-49-6/Heparin; 9007-41-4/C-Reactive Protein; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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