The shift from fluoride/oxalate to acid citrate/fluoride blood collection tubes for glucose testing — The impact upon patient results

Blood is a rich biological sample routinely collected in clinical and epidemiological studies. With advancements in high throughput -omics technology, such as metabolomics, epidemiology can now delve more deeply and comprehensively into biological mechanisms involved in the etiology of diseases. However, the impact of the blood collection tube matrix of samples collected needs to be carefully considered to obtain meaningful biological interpretations and understand how the metabolite signatures are affected by different tube types. In the present study, we investigated whether the metabolic profile of blood collected as serum differed from samples collected as ACD plasma, citrate plasma, EDTA plasma, fluoride plasma, or heparin plasma. We identified and quantified 50 metabolites present in all samples utilizing nuclear magnetic resonance (NMR) spectroscopy. The heparin plasma tubes performed the closest to serum, with only three metabolites showing significant differences, followed by EDTA which significantly differed for five metabolites, and fluoride tubes which differed in eleven of the fifty metabolites. Most of these metabolite differences were due to higher levels of amino acids in serum compared to heparin plasma, EDTA plasma, and fluoride plasma. In contrast, metabolite measurements from ACD and citrate plasma differed significantly for approximately half of the metabolites assessed. These metabolite differences in ACD and citrate plasma were largely due to significant interfering peaks from the anticoagulants themselves. Blood is one of the most banked samples and thus mining and comparing samples between studies requires understanding how the metabolite signature is affected by the different media and different tube types.

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Underfilling of vacuum blood collection tubes leads to increased lactate dehydrogenase activity in serum and heparin plasma samples

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0616 ◽

2020 ◽

Vol 58 (2) ◽

pp. 213-221

Author(s):

Nick Neuwinger ◽

Dirk Meyer zum Büschenfelde ◽

Rudolf Tauber ◽

Kai Kappert

Keyword(s):

Lactate Dehydrogenase ◽

Healthy Volunteers ◽

Room Temperature ◽

Blood Collection ◽

Lactate Dehydrogenase Activity ◽

Patient Cohort ◽

Reference Limits ◽

Heparin Plasma ◽

The Impact ◽

Blood Collection Tubes

AbstractBackgroundLactate dehydrogenase (LD) activity is routinely monitored for therapeutic risk stratification of malignant diseases, but is also prone to preanalytical influences.MethodsWe systematically analyzed the impact of defined preanalytical conditions on the hemolysis-susceptible parameters LD, potassium (K) and hemolysis index in vacuum blood collection tubes (serum [SE], heparin plasma [HP]). Blood was collected by venipuncture from healthy volunteers. Tubes were either filled or underfilled to approximately 50%, then processed directly or stored at room temperature for 4 h. Potassium (K), sodium (Na), chloride (Cl), LD, creatine kinase (CK), total cholesterol, and indices for hemolysis, icterus, and lipemia were analyzed. Filling velocity was determined in a subset of tubes. Findings in healthy volunteers were reconfirmed in an in-patient cohort (n = 74,751) that was analyzed for plasma yield and LD data distribution.ResultsLD activity was higher in HP compared to SE. Underfilling led to higher LD values (SE: +21.6%; HP: +28.3%), K (SE: +4.2%; HP: +5.3%), and hemolysis index (SE: +260.8%; HP: +210.0%), while other analytes remained largely unchanged. Filling velocity of tubes was approximately 3-fold higher in the first half compared to the second half in both HP and SE collection tubes. Importantly, plasma yield also inversely correlated with LD in routine patients. By calculating reference limits, the lowest plasma yield quartile of the patient cohort displayed LD values clearly exceeding current reference recommendations.ConclusionsUnderfilling of tubes leads to a higher proportion of blood aspirated with high velocity and relevant elevations in LD. This finding should be considered in cases of clinically implausible elevated LD activities.

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Optimization of Preanalytical Variables for cfDNA Processing and Detection of ctDNA in Archival Plasma Samples

BioMed Research International ◽

10.1155/2021/5585148 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Marijana Nesic ◽

Julie S. Bødker ◽

Simone K. Terp ◽

Karen Dybkær

Keyword(s):

Nucleic Acid ◽

B Cell Lymphoma ◽

Circulating Tumor Dna ◽

Blood Collection ◽

Plasma Samples ◽

Cell Free Dna ◽

Blood Samples ◽

Free Dna ◽

The Impact ◽

Blood Collection Tubes

DNA released from cells into the peripheral blood is known as cell-free DNA (cfDNA), representing a promising noninvasive source of biomarkers that could be utilized to manage Diffuse Large B-Cell Lymphoma (DLBCL), among other diseases. The procedure for purification and handling of cfDNA is not yet standardized, and various preanalytical variables may affect the yield and analysis of cfDNA, including the purification kits, blood collection tubes, and centrifugation regime. Therefore, we aimed to investigate the impact of these preanalytical variables on the yield of cfDNA by comparing three different purification kits DNeasy Blood & Tissue Kit (Qiagen), QIAamp Circulating Nucleic Acid Kit (Qiagen), and Quick-cfDNA Serum & Plasma Kit (Zymo Research). Two blood collection tubes (BCTs), EDTA-K2 and Cell-Free DNA (Streck), stored at four different time points before plasma was separated and cfDNA purified, were compared, and for EDTA tubes, two centrifugation regimes at 2000 × g and 3000 × g were tested. Additionally, we have tested the utility of long-term archival blood samples from DLBCL patients to detect circulating tumor DNA (ctDNA). We observed a higher cfDNA yield using the QIAamp Circulating Nucleic Acid Kit (Qiagen) purification kit, as well as a higher cfDNA yield when blood samples were collected in EDTA BCTs, with a centrifuge regime at 2000 × g . Moreover, ctDNA detection was feasible from archival plasma samples with a median storage time of nine years.

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Performance of RNA purification kits and blood collection tubes in the Extracellular RNA Quality Control (exRNAQC) study

10.1101/2021.05.11.442610 ◽

2021 ◽

Author(s):

◽

Jasper Anckaert ◽

Francisco Avila Cobos ◽

Anneleen Decock ◽

Jill Deleu ◽

...

Keyword(s):

Quality Control ◽

Messenger Rna ◽

Performance Metrics ◽

Blood Collection ◽

Sample Collection ◽

Blood Draw ◽

Extracellular Rna ◽

Rna Purification ◽

The Impact ◽

Blood Collection Tubes

The use of blood-based extracellular RNA (exRNA) as clinical biomarker requires the implementation of a validated procedure for sample collection, processing and profiling. So far, no study has systematically addressed the pre-analytical variables affecting transcriptome analysis of exRNAs. In the exRNAQC study, we evaluated 10 blood collection tubes, 3 time points between blood draw and downstream processing, and 8 RNA purification methods using the supplier-specified minimum and maximum biofluid input volumes. The impact of these pre-analytics is assessed by deep transcriptome profiling of both small and messenger RNA from healthy donors' plasma or serum. Experiments are conducted in triplicate (for a total of 276 transcriptomes) using 189 synthetic spike-in RNAs as processing controls. When comparing blood tubes, so-called blood preservation tubes do not stabilize RNA very well, as is reflected by increasing RNA concentration and number of detected genes over time, and by compromised reproducibility. We also document large differences in RNA purification kit performance in terms of sensitivity, reproducibility, and observed transcriptome complexity. Our results are summarized in 11 performance metrics that enable an informed selection of the most optimal sample processing workflow for your own experiments. In conclusion, we put forward robust quality control metrics for exRNA quantification methods with validated standard operating procedures (SOPs) for processing, representing paramount groundwork for future exRNA-based precision medicine applications.

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Addition of protease inhibitors to EDTA containing blood collection tubes does not deliver significant advantage for preservation of plasma for down-stream analysis

Clinical Proteomics and Bioinformatics ◽

10.15761/cpb.1000115 ◽

2016 ◽

Vol 1 (3) ◽

Author(s):

Mahboob S ◽

Ahn SB ◽

Mohamedali A ◽

Amirkhani A ◽

Tan S-H ◽

...

Keyword(s):

Protease Inhibitors ◽

Blood Collection ◽

Blood Collection Tubes

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Comparison of Blood Collection Tubes from Three Different Manufacturers for the Collection of Cell-Free DNA for Liquid Biopsy Mutation Testing

Journal of Molecular Diagnostics ◽

10.1016/j.jmoldx.2017.06.004 ◽

2017 ◽

Vol 19 (5) ◽

pp. 801-804 ◽

Cited By ~ 35

Author(s):

Christina Alidousty ◽

Danielle Brandes ◽

Carina Heydt ◽

Svenja Wagener ◽

Maike Wittersheim ◽

...

Keyword(s):

Liquid Biopsy ◽

Mutation Testing ◽

Blood Collection ◽

Cell Free Dna ◽

Free Dna ◽

Blood Collection Tubes

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Stability of Phenytoin in Blood Collected in Vacuum Blood Collection Tubes

Therapeutic Drug Monitoring ◽

10.1097/00007691-199001000-00016 ◽

1990 ◽

Vol 12 (1) ◽

pp. 85-89 ◽

Cited By ~ 8

Author(s):

Roy C. Parish ◽

Tamra Alexander

Keyword(s):

Blood Collection ◽

Blood Collection Tubes

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Avoidable Blood Loss in Critical Care and Patient Blood Management: Scoping Review of Diagnostic Blood Loss

Journal of Clinical Medicine ◽

10.3390/jcm11020320 ◽

2022 ◽

Vol 11 (2) ◽

pp. 320

Author(s):

Philipp Helmer ◽

Sebastian Hottenrott ◽

Andreas Steinisch ◽

Daniel Röder ◽

Jörg Schubert ◽

...

Keyword(s):

Intensive Care ◽

Blood Loss ◽

Blood Volume ◽

Scoping Review ◽

Relevant Information ◽

Blood Collection ◽

Patient Blood Management ◽

Blood Management ◽

Intensive Care Patients ◽

Blood Collection Tubes

Background: Anemia remains one of the most common comorbidities in intensive care patients worldwide. The cause of anemia is often multifactorial and triggered by underlying disease, comorbidities, and iatrogenic factors, such as diagnostic phlebotomies. As anemia is associated with a worse outcome, especially in intensive care patients, unnecessary iatrogenic blood loss must be avoided. Therefore, this scoping review addresses the amount of blood loss during routine phlebotomies in adult (>17 years) intensive care patients and whether there are factors that need to be improved in terms of patient blood management (PBM). Methods: A systematic search of the Medline Database via PubMed was conducted according to PRISMA guidelines. The reported daily blood volume for diagnostics and other relevant information from eligible studies were charted. Results: A total of 2167 studies were identified in our search, of which 38 studies met the inclusion criteria (9 interventional studies and 29 observational studies). The majority of the studies were conducted in the US (37%) and Canada (13%). An increasing interest to reduce iatrogenic blood loss has been observed since 2015. Phlebotomized blood volume per patient per day was up to 377 mL. All interventional trials showed that the use of pediatric-sized blood collection tubes can significantly reduce the daily amount of blood drawn. Conclusion: Iatrogenic blood loss for diagnostic purposes contributes significantly to the development and exacerbation of hospital-acquired anemia. Therefore, a comprehensive PBM in intensive care is urgently needed to reduce avoidable blood loss, including blood-sparing techniques, regular advanced training, and small-volume blood collection tubes.

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