Sodium citrate blood contamination by K<sub>2</sub>‐ethylenediaminetetraacetic acid (<scp>EDTA</scp>): impact on routine coagulation testing

Lima-Oliveira, Gabriel; Salvagno, Gian Luca; Danese, Elisa; Favaloro, Emmanuel J.; Guidi, Gian Cesare; Lippi, Giuseppe

doi:10.1111/ijlh.12301

Cited by 20 publications

(12 citation statements)

References 21 publications

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“…This has been subsequently confirmed in another study [45]. Although it seems difficult to reconcile the conflicting results emerged from different studies, it may be that a random order of draw using poor sample collection techniques and/or during difficult venipunctures may result in cross-contamination of sample tubes, thus ultimately jeopardizing the quality of testing [46,47]. This idea is supported by a study of Berg et al [48], which showed that only 6% of blood collections were performed using the conventional manufacturer prescribed closed loop system in a major emergency department in the UK.…”

Section: The Order Of Draw -Myth or Science?mentioning

confidence: 89%

Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE)

Lippi¹,

Banfi²,

Church³

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Laboratory diagnostics develop through different phases that span from test ordering (pre-preanalytical phase), collection of diagnostic specimens (preanalytical phase), sample analysis (analytical phase), results reporting (postanalytical phase) and interpretation (post-postanalytical phase). Although laboratory medicine seems less vulnerable than other clinical and diagnostic areas, the chance of errors is not negligible and may adversely impact on quality of testing and patient safety. This article, which continues a biennial tradition of collective papers on preanalytical quality improvement, is aimed to provide further contributions for pursuing quality and harmony in the preanalytical phase, and is a synopsis of lectures of the third European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled 'Preanalytical quality improvement. In pursuit of harmony' (Porto, 20-21 March 2015). The leading topics that will be discussed include unnecessary laboratory testing, management of test request, implementation of the European Union (EU) Directive on needlestick injury prevention, harmonization of fasting requirements for blood sampling, influence of physical activity and medical contrast media on in vitro diagnostic testing, recent evidence about the possible lack of necessity of the order of draw, the best practice for monitoring conditions of time and temperature during sample transportation, along with description of problems emerging from inappropriate sample centrifugation. In the final part, the article includes recent updates about preanalytical quality indicators, the feasibility of an External Quality Assessment Scheme (EQAS) for the preanalytical phase, the results of the 2nd EFLM WG-PRE survey, as well as specific notions about the evidence-based quality management of the preanalytical phase.

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Section: The Order Of Draw -Myth or Science?mentioning

confidence: 89%

Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE)

Lippi¹,

Banfi²,

Church³

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Mohri and Rezapoor (2009) also demonstrated the difference in estimating routine biochemical parameters using EDTA, heparin and citrate tubes. The chelating nature of EDTA and its influence on samples collected for blood clotting assay and serum electrolytes was shown by Lima-Oliveria et al (2014, 2015). Cross-contamination of heparinized or citrated blood with EDTA was shown to adversely affect the blood clotting assay and also the electrolyte levels, grossly underestimating them.…”

Section: Resultsmentioning

confidence: 94%

Effect of various anticoagulants on the bioanalysis of drugs in rat blood: implication for pharmacokinetic studies of anticancer drugs

Kulkarni¹,

Karanam

Gurjar

et al. 2016

SpringerPlus

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BackgroundPharmacokinetic studies are vital in development and optimization of drugs. While blood samples can be collected either in EDTA, heparin or citrate containing tubes for the estimation of drug levels in plasma, EDTA tubes are more commonly used. The purpose of this study was to evaluate the effects of anticoagulants on bioanalysis of drugs. Six drugs used extensively in cancer therapy were selected. Albino wistar rats (N = 6 per drug) were dosed with one of the following drugs intraperitoneally—pemetrexed (50 mg/kg), imatinib (50 mg/kg), erlotinib (25 mg/kg), meropenem (60 mg/kg), 6-mercaptopurine (20 mg/kg) and voriconazole (6 mg/kg). Blood samples were collected 2 h after dosing (1 h in 6-mercaptopurine group due to short half-life) by terminal bleeding from the retro-orbital plexus. Blood was collected in each of Disodium ETDA, heparin, trisodium citrate (TSC) and no anticoagulant (plain) tubes. Drug levels in these samples were determined by validated HPLC assays. ANOVA with Tukey’s post hoc test was performed to identify statistically significant differences in drug concentrations in anticoagulant tubes. p < 0.05 was considered statistically significant.ResultsSignificant differences in concentration between anticoagulant tubes was observed in case of erlotinib (p = 0.013) and meropenem (p = 0.00), while borderline statistical significance for pemetrexed (p = 0.076). TSC tubes overestimated erlotinib levels, heparin tubes underestimated meropenem concentrations and EDTA tubes overestimated pemetrexed concentrations.ConclusionsCareful selection of anti-coagulant is necessary for accurate characterization of pharmacokinetics of drugs. Routine use of EDTA tubes may lead to erroneous interpretation of pharmacokinetic data.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3770-4) contains supplementary material, which is available to authorized users.

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“…Accordingly, depending on the APTT reagent, and its specific formulation and intended application (heparin monitoring; sensitivity or not to LAC; hemostasis testing), different APTT reagents will show different sensitivities to each of these. Spurious prolongations of APTT clotting times are also frequently observed due to pre-analytical or analytical issues, such as sample contamination with heparin or ethylenediaminetetraacetic acid salts [73], insufficient filling of primary blood tubes [74], the presence of hypertriglyceridemia and hyperbilirubinemia [75] and delayed sample centrifugation (FIGURE 2) [76].…”

Section: First-line (Routine Coagulation) Testsmentioning

confidence: 99%

“…Indeed, just as APTT reagents are designed for multiple uses, the PT is primarily utilized in the laboratory setting to monitor patients on VKA therapy, and many reagents are only weakly sensitive to hemostasis defects. Spurious prolongation can also be encountered when the sample is contaminated with ethylenediaminetetraacetic acid salts [73] or (heavily) contaminated with heparin, or suffers from insufficient filling of primary blood tubes [74].…”

Section: First-line (Routine Coagulation) Testsmentioning

confidence: 99%

Detection of mild inherited disorders of blood coagulation: current options and personal recommendations

Lippi

Pasalic

Favaloro

2015

Expert Review of Hematology

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Although assessment of prior personal and familial bleeding history is an important aspect of the diagnosis of bleeding disorders, patients with mild inherited bleeding disorders are sometimes clinically asymptomatic until presented with a hemostatic challenge. However, bleeding may occur after incursion of trauma or surgery, so detection of these conditions reflects an important facet of clinical and laboratory practice. Mild bleeding disorders may be detected as a result of family studies or following identification of abnormal values in first-line screening tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and global platelet function screen testing, such as the platelet function analyzer. Following determination of abnormal screening tests, subsequent investigation should follow a systematic approach that targets specific diagnostic tests, and including factor assays, full platelet function assays and more extensive specialized hemostasis testing. The current report provides a personal overview on inherited disorders of blood coagulation and their detection.

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Sodium citrate blood contamination by K₂‐ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing

Abstract: The results of this investigation show that contamination of citrated blood with as much as 29% of K2 EDTA blood generates a significant bias in results of routine clotting assays. This has serious implications for patient safety and management.

Cited by 20 publications

References 21 publications

Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE)

Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE)

Effect of various anticoagulants on the bioanalysis of drugs in rat blood: implication for pharmacokinetic studies of anticancer drugs

Detection of mild inherited disorders of blood coagulation: current options and personal recommendations

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Sodium citrate blood contamination by K2‐ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing

Abstract: The results of this investigation show that contamination of citrated blood with as much as 29% of K2 EDTA blood generates a significant bias in results of routine clotting assays. This has serious implications for patient safety and management.

Cited by 20 publications

References 21 publications

Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE)

Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE)

Effect of various anticoagulants on the bioanalysis of drugs in rat blood: implication for pharmacokinetic studies of anticancer drugs

Detection of mild inherited disorders of blood coagulation: current options and personal recommendations

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Sodium citrate blood contamination by K₂‐ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing