De Biologie Clinique Research Articles

SFBC Working Group on sources of errors in laboratory medicine: objectives and key areas of work

Laboratory medicine plays a crucial role in patient care, contributing to approximately 70% of clinical decisions. In collaboration with clinicians, laboratory medicine specialists perform analyses that are useful for diagnosis, screening and prevention. Laboratories are known for their efficiency, which is reached through a rigorous quality system. However, errors can occur, especially given the complexity of the total testing process. These errors may lead to severe consequences, such as incorrect diagnoses or delays in treatment. Errors can occur at every stage of the total testing process, those related to the pre-analytical phase being the most prevalent. To reduce medical errors related to laboratory processes, it is essential to provide training for medical and paramedical staff, optimize production automation, and leverage technological advancements. These considerations have led to the creation of a French Working Group on Sources of Errors in Laboratory Medicine, under the aegis of the French lean society of clinical chemistry and laboratory medicine (Société Française de Biologie Clinique - SFBC). The objectives of this working group are to produce an educational handbook on sources of errors in laboratory medicine, provide training for clinical chemists, and conducting applied research projects to better understand the mechanisms behind specific errors. Ultimately, the aim is to minimize errors and enhance the quality of laboratory tests.

Verification of the analytical performance of the serum magnesium assay on Abbott Architect ci8200

Magnesium is recognized as the fourth most important cation in the body and the second most abundant intracellular cation, following potassium. Its physiological significance lies in its capacity to form complexes with crucial intracellular anionic ligands, notably ATP, and its ability to compete with calcium for specific binding sites on proteins and cell membranes. Over 300 enzyme reactions rely on magnesium. The concentration of free magnesium within cells determines the magnesium content of these enzymes. Magnesium influences myocardial contraction and the electrical activity of myocardial cells, as well as the specialized conduction systems of the fetus, by modulating the transmembrane movements of ions like sodium, potassium, and calcium. Furthermore, magnesium can affect the contractility of vascular smooth muscle, and alterations in intracellular magnesium levels may impact cell proliferation or contraction. Magnesium is involved in nucleic acid and protein metabolism, intermediary metabolism, energy production, and consumption reactions, and it plays specific roles in various physiological systems such as the neuromuscular and cardiovascular systems. Our research aims to assess the analytical accuracy of the serum magnesium assay method utilizing an Abbott kit on the Architect ci8200 automated system in the biochemistry laboratory of Mohammed VI University Hospital of Oujda. The evaluation of the kit's analytical accuracy was conducted within the flexible scope A by conducting a performance analysis on the Architect ci8200. We examined repeatability, reproducibility, measurement imprecision, and compared results between two Architect ci8200 instruments. All findings align with the acceptability criteria recommended by the supplier and the Valtec protocol of the Société Française de Biologie Clinique (SFBC), indicating overall satisfactory outcomes for the study. The Architect ci8200 automated system demonstrated satisfactory analytical performance for reliably determining serum magnesium levels. Method verification in medical laboratories is essential to guarantee the accuracy, precision, and reliability of test results. Verification entails confirming that the test method used is suitable for its intended purpose, yields result consistent with the claimed performance characteristics, and meets the laboratory's quality control and quality assurance standards.

Verification of the analytical performance of the serum phosphorus assay on the Abbott Alinity ci®: Experience of the central laboratory Mohammed VI University Hospital of Oujda

Introduction: In our study, we aimed to evaluate the analytical performance of the serum phosphorus determination method using an Abbott kit on the Alinity c automaton at the biochemistry laboratory of Mohammed VI University Hospital of Oujda. Materials and methods: We evaluated the performance of the kit using flexible scope A and conducted a thorough performance study on the Alinity c automaton. This study encompassed assessments of repeatability, reproducibility and comparisons of results obtained from two Alinity c automatons. Results: The obtained results met the acceptability criteria recommended by the supplier and the French Society of Clinical Biology(Société Française de Biologie Clinique SFBC) Valtec protocol, indicating overall satisfaction with the study. The Alinity c automaton exhibited the necessary analytical performance to ensure accurate and dependable determination of phosphorus levels. Discussion: Ensuring accurate and reliable results, the verification of the serum phosphorus determination method in the medical laboratory is crucial. This process entails implementing quality control measures, calibration, and comparing with established reference methods. It guarantees that the laboratory's phosphorus testing method is precise, accurate, and compliant with industry standards, thereby upholding the quality of patient care. Conclusion: The verification study of the serum phosphorus determination method yielded satisfactory results, providing high reliability to the test results from the central laboratory at Mohammed VI University Hospital of Oujda. This verification study serves as a strong foundation in the accreditation process, ensuring the accuracy and quality of laboratory testing, and enhancing the overall reliability of patient care

Verification of the analytical performance of the serum total cholesterol assay on Abbott Architect ci8200

Serum total cholesterol measurement is an essential aspect of preventive healthcare as high levels of cholesterol are linked to various diseases such as atherosclerosis, heart attacks, and strokes. Serum cholesterol measurement is a simple blood test that assesses the levels of cholesterol in the bloodstream. It is an important diagnostic tool that helps healthcare professionals evaluate a patient's risk of developing cardiovascular disease and make decisions regarding treatment and lifestyle changes. Our study aims to verify the analytical performance of the serum total cholesterol assay method using an Abbott kit on the Architect ci8200 automated system in the biochemistry laboratory of the Mohammed VI University Hospital of Oujda. The analytical performance of the kit was verified through flexible scope A by performing a performance study on the Architect ci8200. We evaluated the repeatability, the reproducibility, the imprecision of the measurements and the comparison between two Architect ci8200 automatons. All the results obtained are in conformity with the acceptability criteria recommended by the supplier and the Valtec protocol of the ‘Société Française de Biologie Clinique’ (SFBC), and the study is globally satisfactory. The analytical performance of the Architect ci8200 automated system was satisfactory for a reliable determination of total cholesterol. Verification of methods of dosage in the medical laboratory is crucial to ensure the accuracy, precision, and reliability of laboratory test results. Verification involves confirming that the test method employed is appropriate for the intended use, produces results that are consistent with the claimed performance characteristics, and meets the laboratory's quality control and quality assurance requirements.

Verification of the analytical performance of the serum gamma-glutamyl transferase assay on the Abbott Alinity ci®: Experience of the biochemistry laboratory of the Mohammed VI university hospital of Oujda

Introduction: As part of our study, we set out to evaluate the analytical performance of the gamma-glutamyl transferase (GGT) assay using an Abbott kit on the Alinity ci® automated system in the biochemistry laboratory of the CHU Mohammed VI in Oujda. Materials and methods: This study assessed the repeatability and reproducibility of Alinity ci® and compared the results obtained by the Alinity ci® and Architect ci-8200® automated systems. Results: The results obtained met the acceptability criteria recommended by the supplier and the Valtec protocol of the Société Française de Biologie Clinique (SFBC), demonstrating overall satisfaction with the study. The Alinity ci® automated system demonstrated the analytical performance required for accurate and reliable determination of GGT levels. Discussion: Validation of an analytical method is an essential step in guaranteeing that the result obtained is as close as possible to the reference value of a sample. Several standards and technical guides set out requirements for the performance criteria of an analytical method, notably NF EN ISO 15 189. Conclusion: the verification study of the GGT assay method produced satisfactory results, providing a high level of reliability for analysis results from the central laboratory of the CHU Mohammed VI d'Ouja. This work forms an essential basis for developing an accreditation procedure, which is part of the quality approach to which our laboratory is committed.

Recommendations for the application and follow-up of quality controls in medical laboratories

This is a translation of the paper “Recommendations for the application and follow-up of quality controls in medical biology laboratories” published in French in the journal Annales de Biologie Clinique (Recommandations pour la mise en place et le suivi des contrôles de qualité dans les laboratoires de biologie médicale. Ann Biol Clin (Paris). 2019;77:577-97.). The recommendations proposed in this document are the result of work conducted jointly by the Network of Accredited Medical Laboratories (LABAC), the French Society of Medical Biology (SFBC) and the Federation of Associations for External Quality Assessment (FAEEQ). The different steps of the implementation of quality controls, based on a risk analysis, are described. The changes of reagent or internal quality control (IQC) materials batches, the action to be taken in case of non-conform IQC results, the choice of external quality assessment (EQA) scheme and interpretation of their results as well as the new issue of analyses performed on several automatic systems available in the same laboratory are discussed. Finally, the concept of measurement uncertainty, the robustness of the methods as well as the specificities of near-patient testing and rapid tests are described. These recommendations cannot apply for all cases we can find in medical laboratories. The implementation of an objective alternative strategy, supported with documented evidence, might be equally considered.

Added value of hepcidin quantification for the diagnosis and follow-up of anemia-related diseases.

Iron homeostasis is based on a strict control of both intestinal iron absorption and iron recycling through reticulo-endothelial system. Hepcidin controls the iron fluxes in order to maintain sufficient iron levels for erythropoietic activities, hemoproteins synthesis or enzymes function, but also to limit its toxic accumulation throughout the body. Hepcidin expression is regulated by various stimuli: inflammation and iron stimulate the production of the peptide, while anemia, erythropoiesis and hypoxia repress its production. Regulation of hepcidin expression is not so simple in complex pathological situations such as hemolytic anemia, cancer or chronic inflammation. Serum hepcidin quantification in association with the diagnostic tests currently available is quite promising for the diagnosis or the follow-up of anemia in those conditions. This study is part of the working group «Clinical interests of hepcidin quantification» of the Société française de biologie clinique.

Evaluation of the quality of clinical practice guidelines published in the Annales de Biologie Clinique with the help of the EFLM checklist

Several tools are available to help evaluate the quality of clinical practice guidelines (CPG). The AGREE instrument (Appraisal of guidelines for research & evaluation) is the most consensual tool but it has been designed to assess CPG methodology only. The European federation of laboratory medicine (EFLM) recently designed a check-list dedicated to laboratory medicine which is supposed to be comprehensive and which therefore makes it possible to evaluate more thoroughly the quality of CPG in laboratory medicine. In the present work we test the comprehensiveness of this check-list on a sample of CPG written in French and published in Annales de biologie clinique (ABC). Thus we show that some work remains to be achieved before a truly comprehensive check-list is designed. We also show that there is some room for improvement for the CPG published in ABC, for example regarding the fact that some of these CPG do not provide any information about allowed durations of transport and of storage of biological samples before analysis, or about standards of minimal analytical performance, or about the sensitivities or the specificities of the recommended tests.

Recommendations for the selection and alignment techniques for the determination of creatinine

In 2010, a working group from the French Society of Clinical Chemistry (Société française de biologie clinique -SFBC) and the French Society of Nephrologie (SN) make a proposal to up-date the guidelines for measuring plasma creatinine.

Évaluation des performances analytiques d’une méthode Elisa pour le dosage du GDF-15 plasmatique

Summary Background Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β (TGFβ) superfamily. The growing interest for its prognostic value in acute coronary syndromes (ACS) and pulmonary embolism lead us to evaluate a recently commercialised immunoenzymatic Elisa kit. Methods The DuoSet ® Elisa kit (R&D Systems ® ) was evaluated according to the Societe francaise de biologie clinique (SFBC) validation protocol. Pre-analytical conditions were tested. GDF-15 was quantified in two groups: “healthy” individuals and patients with troponin greater than 0,15 μg/L. Results The method was validated. Heparinated plasma at a one-eighth dilution was selected for the study. The stability of GDF-15 allows several freeze/thaw cycles. Medians of the GDF-15 levels in the two populations (827 ng/L versus 3268 ng/L) were significantly different. Conclusion The DuoSet ® Elisa kit can be used to quantify GDF-15 in human serum and plasma. This will allow us to study GDF-15 prognostic interest in different clinical settings like ACS and pulmonary embolism.

Recommandations préanalytiques pour les analyses de protéomique clinique des fluides biologiques

Research of new diagnosis or prognosis biomarkers is a major challenge for the management of patients with complex pathologies like cancer. Clinical proteomics is one of the recent approaches to identify these biomarkers in biological fluids. Over the last five years, many problems related to the variability and the quality control of these analyses have been observed. This was notably related to the different preanalytical status of each sample. A strong need for standardization of the critical preanalytical phases (collection, transport, processing, storage...) has been therefore recognized. With this goal in mind, working groups of the "Institut national du cancer" (INCa) and the "Société française de biologie clinique" (SFBC) proposed here preanalytical proteomics guidelines for the most common biological fluids: plasma, serum, urine and cerebrospinal fluid. To goal is to provide the basis for the harmonization of the procedures in clinical laboratories and biobanks to allow an optimal use of biological collections.

Propositions pour l’expression standardisée des résultats d’HbA1c

The 2007 international consensus about the standardization of HbA(1c) determination and expression of results is progressively implemented in most countries. In France, a common working group of the Société française de biologie clinique (SFBC) and the Société francophone de diabétologie (SFD) has expressed the following recommendations. HbA(1c) results are expressed in percentage of total hemoglobin and in mmol HbA(1c)/mol Hb, but are not converted into estimated average glucose. A table indicating the correspondence between HbA(1c) and estimated average glucose may be given with the results, subject to precautions of interpretation at the individual level.

Guides de pratique clinique: trions-les*

A growing number of clinical practice guidelines (CPG) is published. This is understandable because CPG are the corner stone in the evaluation of professional practices (EPP). One cannot deny that EPP is necessary. However, in order for the EPP to reach their objectives, which are to use our resources better and to improve health-care, CPG at our disposal should be of good quality, both in their form and in their content. This is not always the case. What is more, health-care professionals are often not properly trained to distinguish "good" from "not so good" CPG. In this context, the Société française de biologie clinique has created a working group on "CPG and Evidence-Based Laboratory Medicine (EBLM)". One of the main objectives of our group is to publish critical appraisals of CPG on a regular basis in the Annales de Biologie Clinique (ABC). Thus, the ABC will follow the example set by other medical journals, for example in France: Prescrire. We will more particularly appraise CPGs in relation with laboratory medicine. In this first article, we describe the methods that we will use in order to distinguish "good" from "not so good" CPG. Just like Prescrire as well as like many others, our first tool will be the AGREE instrument, which is quite consensual at an international level. The AGREE tool makes it possible to appraise quite easily, and in a reproducible way, the methodological quality of CPG. We also briefly discuss the more complicated methods that can be used to make judgments about the content of CPG, bearing in mind that equity, patients' autonomy, balancing risks and benefits, are the four universal principles of medical ethics, that is of good medicine, that is of EB(L)M.

Evaluation of the Unicel DXC 600 (Beckman Coulter) and comparison with Integra 800 (Roche Diagnostics)

The Unicel DXC 600 is an automated analytical system from Beckman Coulter for measuring usual biochemistry parameters (electrolytes, substrates and enzymatic activities), therapeutic drugs, drugs of abuse and specific proteins. According to the "Société française de biologie clinique (SFBC)" validation protocol, we tested the following parameters: electrolytes (sodium, potassium, chloride, total CO2), substrates (uric acid, calcium, phosphate, glucose, creatinine, urea, cholesterol, HDL cholesterol, bilirubin, iron, triglycerides), enzymes (ALAT, ASAT, amylase, CK, GGT, LDH, lipase, ALP), total proteins and specific proteins (albumin, CRP, haptoglobin). The results confirm the excellent analytical performances regarding imprecision. The comparison study shows differences between values obtained with Unicel DXC 600 and Integra 800 (Roche diagnostics), leading to the use of correcting factors for some parameters.

Plasma Homocysteine Measurement with Ion Exchange Chromatography (Jeol Aminotac 500): A Comparison with the Abbott IMx Assay

Objective: We evaluated ion exchange chromatography (IEC) on the Jeol Aminotac 500 analyzer for total homocysteine (tHcy) determination and compared it with an immunoassay method using fluorescence polarization on an Abbott IMx analyzer. Methods: IEC method validation (linearity, limit of detection, precision, interference) was made according to the French Biology Society guidelines (Société Française de Biologie Clinique). Moreover, during a 2-month period, 55 plasma samples from patients scheduled for routine tHCy measurement were assayed by both methods for determining correlation. Results: The IEC method was found linear up to at least 190 µmol/l, and the limit of detection was 1.6 µmol/l. Precision was studied with 3 controls at 6, 15 and 30 µmol/l. Intra-assay coefficients of variation (n = 14) were 8.3, 3.1 and 2.3%, respectively, and inter-assay coefficients of variation (n = 15) were 9.6, 5.1 and 4.9%, respectively. No interference was found with other sulfur-containing amino acids (methionine, cysteine). An excellent agreement was found between IEC and fluorescence polarization (Deming regression; y = 0.99x – 1.23; r = 0.97; p < 0.001). Conclusion: The IEC method for tHcy measurement shows adequate precision and correlates highly with the IMx assay. The IEC method is more time-consuming but less expensive in reagent cost and allows simultaneous determination of plasma methionine concentration which may help to explain the underlying mechanism responsible for hyperhomocysteinemia.

Évaluation comparée des analyseurs dimension RXL ® et Cobas ® Intégra 700

The Dimension RXL ® and Cobas ® Integra 700 analysers are multi-parameter biochemical auto-analysers which can be considered to fall within the same range of instrument in view of their analytical possibilities (number and variety of in line tests available) and their theoretical throughput, ranging between 600 and 800 tests per hour, depending on whether or not an ionogram is included. These auto-analysers are well suited to emergency services and to biochemical laboratories with a medium volume of activity. The purpose of this paper is to compare the technical performance of these two analysers for a limited number of analytes, the determination of which occasionally gives rise to difficulties. The assessment made concerns only plasma and urine ionograms, catalytic activity of LDHs, C reactive protein (CRP), calcaemia, serum iron, vancomycinaemia, creatinine in plasma and urine, proteinuria and determination of benzodiazepines in urine. The recommendations of the technical validation protocol (Valtec) published by the Société française de biologie clinique (French clinical biology society) were strictly followed throughout this study. For the Cobas ® Integra 700 analyser, the results obtained show essentially a certain weakness on the urine ionogram. This weakness is reflected in imprecise chloride readings and inexact sodium, potassium and chloride values with respect to the chosen comparison techniques. As far as Dimension RXL ® is concerned, this analyser proved to give imprecise results for urine benzodiazepines as well as inexact CRP readings. For the other analytes, the degree of imprecision is acceptable and the transferability of patients results between the two auto-analysers is possible. In addition, the visible interference thresholds (haemolysis, turbidity and bilirubin) are generally-speaking lower on the Dimension RXL ®. Finally, both analysers are easy to use and the Cobas ® Integra 700 works station proves to be very user-friendly.

Évaluation d'un automate d'immunoanalyse : le vitros ECi

The assessment of the Vitros ECi, an automated chemiluminescence system, was carried out according to the Société française de biologie clinique (SFBC) protocol. Analytical performances of the ECi system (precision, linearity, sensitivity…) and the reagents were recorded from 2000 tests including controls, with good results. In almost all cases, the within and between-run coefficients of variation were acceptable and often less than 10 %. Comparative study ECi versus Elecsys with a panel of 921 sera belonging to different clinical patterns showed a good correlation for the different analyses within a range between 0,77 and 0,99. Finally, the software was globally satisfactory for routine and emergency diagnostic needs.

Évaluation des performances analytiques de l'analyseur cobas ®integra 700

The Cobas Integra 700 is a closed multiparametrical analyser with captive reagents allowing to test usual biochemistry parameters (electrolytes, substrates and enzymatic activities), but also therapeutic drugs, drugs of abuse, toxics and specific proteins. During our experimental work, we evaluated the analytical performances of the Cobas Integra 700 according to the Société française de biologie clinique (SFBC) technique validation protocol (Valtec 97) for the following analytes: sodium, potassium, iron, urea nitrogen, creatin kinase, amikacin, IgG, albumin and C-reactive protein (CRP) in blood, sodium, potassium, creatinine and proteins in urine. The results we obtained allow to confirm the excellent analytical performances regarding imprecision and operational characteristics. On the other hand, concerning some analytes, we noticed an inaccuracy with the selected comparison techniques, especially for CRP, urine sodium and proteins. In conclusion and considering its practicability (automated daily servicing, software user-friendliness, automated reagents reconstitution…), the Cobas Integra 700 seems to us well suited for biochemistry laboratories performing from 1,500 to 3,000 daily tests.

Évaluation du mercury 16 (nova biomedical) : application aux profils d'urgence et de routine sur sang total et urine en néphrologie

The aim of this work was to assess the performances of Mercury 16 (sodium, potassium, chloride, total CO 2, glucose, urea, creatinine and hematocrit on whole blood, plasma, serum, urine, dialysate and cerebrospinal fluid) in following critical situations: use without formation, use with minimal maintenance and short laboratory responses time (less than 5 min.) on whole blood and urine and on icteric samples. The results obtained on whole blood and plasma were quite similar and the correlations between Mercury 16 - whole blood, CX7 Delta (Beckman) and STKS (Coulter) before and after dialysis (30 patients) were highly significant. Considering the well known potential bilirubin interference on glucose, creatinine and blood urea nitrogen determinations, our study showed the insensitivity of Mercury 16 to bilirubin (concentrations up 200 μmol/L to 700 μmol/L as total bilirubin). The correlations between Mercury 16 and CX7 Delta in 42 urine were highly significant. Finally, considering the analytical specifications, the short and easy maintenance, the management of analytical and patient data and reagents, the turnaround time (less than 2 min. for all mesured tests), the possibility of a link (direct or via a specific station) to central laboratory system, Mercury 16 is well adapted to any critical care situations and so, to point care of testing, in agreement with GBEA and Société française de biologie clinique recommendations.

Glycohemoglobin assays evaluated in a large-scale quality-control survey

We report the results of a national quality-control survey on glycohemoglobin (GHb), monitored in France by the Société Française de Biologie Clinique on behalf of the authority of the "Agence du Médicament." A sample of lyophilized hemolysate was sent to 3109 laboratories. Results were obtained from 2770 laboratories. HbA1C, HbA1, and total GHb were measured by 50%, 24%, and 26% of the participants, respectively. Of these measurements, 79% of the HbA1C results and 76% of the total GHb results, but only 48% of the HbA1 results, were within the +/- 20% limits of the indicated target values. Mean values for the hemolysate ranged from 8% to 11% for HbA1C, from 7% to 12% for HbA1, and from 11% to 13% for total GHb. The interlaboratory CVs ranged from 3% to 20%, according to method used. So, methods used for GHb assay, which are based on various principles, exhibit very different analytical performances. Nonetheless, this large-scale study indicates that some techniques can support transferability of results from laboratory to laboratory.