Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences.

Blood alcohol concentration in the clinical laboratory: a narrative review of the preanalytical phase in diagnostic and forensic testing.

The analysis of blood alcohol concentration (BAC), a pivotal toxicological test, concerns acute alcohol intoxication (AAI) and driving under the influence (DUI). As such, BAC presents an organizational challenge for clinical laboratories, with unique complexities due to the need for forensic defensibility as part of the diagnostic process. Unfortunately, a significant number of scientific investigations dealing with the subject present discrepancies that make it difficult to identify optimal practices in sample collection, transportation, handling, and preparation. This review provides a systematic analysis of the preanalytical phase of BAC that aims to identify and explain the chemical, physiological, and pharmacological mechanisms underlying controllable operational factors. Nevertheless, it seeks evidence for the necessity to separate preanalytical processes for diagnostic and forensic BAC testing. In this regard, the main finding of this review is that no literature evidence supports the necessity to differentiate preanalytical procedures for AAI and DUI, except for the traceability throughout the chain of custody. In fact, adhering to correct preanalytical procedures provided by official bodies such as European federation of clinical chemistry and laboratory medicine for routine phlebotomy ensures both diagnostic accuracy and forensic defensibility of BAC. This is shown to depend on the capability of modern pre-evacuated sterile collection tubes to control major factors influencing BAC, namely non-enzymatic oxidation and microbial contamination. While certain restrictions become obsolete with such devices, as the use of sodium fluoride (NaF) for specific preservation of forensic BAC, this review reinforces the recommendation to use non-alcoholic disinfectants as a means to achieve "error-proof" procedures in challenging operational environments like the emergency department.

Quality of hematology and clinical chemistry results in laboratory and zoo nonhuman primates: Effects of the preanalytical phase. A review.

Most errors in clinical pathology originate in the preanalytical phase, which includes all steps from the preparation of animals and equipment to the collection of the specimen and its management until analyzed. Blood is the most common specimen collected in nonhuman primates. Other specimens collected include urine, saliva, feces, and hair. The primary concern is the variability of blood hematology and biochemistry results due to sampling conditions with the effects of capture, restraint, and/or anesthesia. Housing and diet have fewer effects, with the exception of food restriction to reduce obesity. There has been less investigation regarding the impact of sampling conditions of nonblood specimens.

Recommendation for the design of stability studies on clinical specimens.

OBJECTIVES: Knowledge of the stability of analytes in clinical specimens is a prerequisite for proper transport and preservation of samples to avoid laboratory errors. The new version of ISO 15189:2022 and the European directive 2017/746 increase the requirements on this topic for manufacturers and laboratories. Within the project to generate a stability database of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Preanalytical Phase (WG-PRE), the need to standardise and improve the quality of published stability studies has been detected, being a manifest deficit the absence of international guidelines for the performance of stability studies on clinical specimens. METHODS: These recommendations have been developed and summarised by consensus of the WG-PRE and are intended primarily to improve the quality of sample stability claims included in information for users provided by assay supplier companies, according to the requirements of the new European regulations and standards for accreditation. RESULTS: This document provides general recommendations for the performance of stability studies, oriented to the estimation of instability equations in the usual working conditions, allowing flexible adaptation of the maximum permissible error specifications to obtain stability limits adapted to the intended use. CONCLUSIONS: We present this recommendation based on the opinions of the EFLM WG-PRE group for the standardisation and improvement of stability studies, with the intention to improve the quality of the studies and the transferability of their results to laboratories.

Quantitative protein mass-spectrometry requires a standardized pre-analytical phase.

OBJECTIVES: Quantitative protein mass-spectrometry (QPMS) in blood depends on tryptic digestion of proteins and subsequent measurement of representing peptides. Whether serum and plasma can be used interchangeably and whether in-vitro anticoagulants affect the recovery is unknown. In our laboratory serum samples are the preferred matrix for QPMS measurement of multiple apolipoproteins. In this study, we investigated the effect of different matrices on apolipoprotein quantification by mass spectrometry. METHODS: Blood samples were collected from 44 healthy donors in Beckton Dickinson blood tubes simultaneously for serum (with/without gel) and plasma (heparin, citrate or EDTA). Nine apolipoproteins were quantified according to standard operating procedure using value-assigned native serum calibrators for quantitation. Tryptic digestion kinetics were investigated in the different matrices by following formation of peptides for each apolipoprotein in time, up to 22 h. RESULTS: In citrate plasma recovery of apolipoproteins showed an overall reduction with a bias of -14.6%. For heparin plasma only -0.3% bias was found compared to serum, whereas for EDTA-plasma reduction was more pronounced (-5.3% bias) and variable with >14% reduction for peptides of apoA-I, A-II and C-III. Digestion kinetics revealed that especially slow forming peptides showed reduced formation in EDTA-plasma. CONCLUSIONS: Plasma anticoagulants affect QPMS test results. Heparin plasma showed comparable results to serum. Reduced concentrations in citrate plasma can be explained by dilution, whereas reduced recovery in EDTA-plasma is dependent on altered proteolytic digestion efficiency. The results highlight the importance of a standardized pre-analytical phase for accurate QPMS applications in clinical chemistry.

Taking a step back from testing: Preanalytical considerations in molecular infectious disease diagnostics.

Recent studies evaluating the preanalytical factors that impact the outcome of nucleic-acid based methods for the confirmation of SARS-CoV-2 have illuminated the importance of identifying variables that promoted accurate testing, while using scarce resources efficiently. The majority of laboratory errors occur in the preanalytical phase. While there are many resources identifying and describing mechanisms for main laboratory testing on automated platforms, there are fewer comprehensive resources for understanding important preanalytical and environmental factors that affect accurate molecular diagnostic testing of infectious diseases. This review identifies evidence-based factors that have been documented to impact the outcome of nucleic acid-based molecular techniques for the diagnosis of infectious diseases.

The preanalytical phase - from an instrument-centred to a patient-centred laboratory medicine.

In order to guarantee patient safety, medical laboratories around the world strive to provide highest quality in the shortest amount of time. A major leap in quality improvement was achieved by aiming to avoid preanalytical errors within the total testing process. Although these errors were first described in the 1970s, it took additional years/decades for large-scale efforts, aiming to improve preanalytical quality by standardisation and/or harmonisation. Initially these initiatives were mostly on the local or national level. Aiming to fill this void, in 2011 the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group "Preanalytical Phase" (WG-PRE) was founded. In the 11 years of its existence this group was able to provide several recommendations on various preanalytical topics. One major achievement of the WG-PRE was the development of an European consensus guideline on venous blood collection. In recent years the definition of the preanalytical phase has been extended, including laboratory test selection, thereby opening a huge field for improvement, by implementing strategies to overcome misuse of laboratory testing, ideally with the support of artificial intelligence models. In this narrative review, we discuss important aspects and milestones in the endeavour of preanalytical process improvement, which would not have been possible without the support of the Clinical Chemistry and Laboratory Medicine (CCLM) journal, which was one of the first scientific journals recognising the importance of the preanalytical phase and its impact on laboratory testing quality and ultimately patient safety.

The preanalytical process in the emergency department, a European survey.

OBJECTIVES: Clinical decision-making in emergency medicine is under constant pressure from demand and performance requirements, with blood tests being a fundamental part of this. However, the preanalytical process has received little attention. Therefore, this study aimed to investigate the quality of preanalytical phase processes in European emergency departments (EDs) from the perspectives of the three main providers: clinicians, nurses, and laboratory specialists. METHODS: This online survey, distributed among European EDs and laboratories, was supported by the European Society for Emergency Nursing (EUSEN), European Society for Emergency Medicine (EuSEM), and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). The size of the centres, the European region, the responder's profession and the country's economic condition were used as co-variables. RESULTS: We included 376 responses from all ED-related professions from 306 European centres. In 66.9% of all ED visits, at least one blood test was performed. Tests were requested mostly by nurses (44.6%) using electronic Order/Entry systems (65.4%). Only a minority (19%) reported not using laboratory quality indicators (QIs). Most responders defined the TAT starting point "when the laboratory receives the sample" (66.1%), defining the goal to be "less than 60 min" (69.9%), but only 42.4% of the centres estimated achieving this goal. CONCLUSIONS: Our survey illustrates the current situation on preanalytical blood sample processing in European EDs from the clinical and laboratory perspectives. The results emphasise the importance of the IT infrastructure and QI usage in this process and highlight some differences between European regions.

Control of non-conformities in the pre-analytical phase at the Bacteriology Laboratory of the Ibn Sina University Hospital in Rabat (Morocco).

INTRODUCTION: The errors in the pre-analytic phase are at the origin of 60 to 85% of the errors in the results proceeded from laboratory. AIM: To evaluate the impact of the pre-analytical phase on the received bacteriology samples received at the medical bacteriology laboratory of Ibn Sina UH in Rabat Morocco in order to propose corrective actions. METHODS: A descriptive and quantitative study of the non-conformities of the pre-analytical phase identified in the central laboratory of medical bacteriology of the Ibn Sina hospital in Rabat over a period of 6 months (from January 01 to July 01, 2020). It concerned samples from various clinical services and care units of Ibn Sina Hospital, as well as external samples. In order to act on these various dysfunctions, we used quality tools such as the Pareto chart and from Ishikawa. RESULTS: We counted 424 cases of pre-analytical NC on 14468 samples received to the Central Laboratory of Bacteriology or 2.93%. These are mainly errors of sample identification and patient identity (59.66%), quality and quantity of samples (25.02%) and problem of conditions of transport and packaging (15.32%). CONCLUSION: Its mastery requires firstly, a close collaboration between the various services, prescribers, samplers and biologists and secondly the respect of each stage of this phase by the hospital staff.

Failure Mode and Effects Analysis (FMEA) at the preanalytical phase for POCT blood gas analysis: proposal for a shared proactive risk analysis model.

OBJECTIVES: Proposal of a risk analysis model to diminish negative impact on patient care by preanalytical errors in blood gas analysis (BGA). METHODS: Here we designed a Failure Mode and Effects Analysis (FMEA) risk assessment template for BGA, based on literature references and expertise of an international team of laboratory and clinical health care professionals. RESULTS: The FMEA identifies pre-analytical process steps, errors that may occur whilst performing BGA (potential failure mode), possible consequences (potential failure effect) and preventive/corrective actions (current controls). Probability of failure occurrence (OCC), severity of failure (SEV) and probability of failure detection (DET) are scored per potential failure mode. OCC and DET depend on test setting and patient population e.g., they differ in primary community health centres as compared to secondary community hospitals and third line university or specialized hospitals. OCC and DET also differ between stand-alone and networked instruments, manual and automated patient identification, and whether results are automatically transmitted to the patient's electronic health record. The risk priority number (RPN = SEV × OCC × DET) can be applied to determine the sequence in which risks are addressed. RPN can be recalculated after implementing changes to decrease OCC and/or increase DET. Key performance indicators are also proposed to evaluate changes. CONCLUSIONS: This FMEA model will help health care professionals manage and minimize the risk of preanalytical errors in BGA.

A deep learning-based system for assessment of serum quality using sample images.

BACKGROUND: Serum quality is an important factor in the pre-analytical phase of laboratory analysis. Visual inspection of serum quality (including recognition of hemolysis, icterus, and lipemia) is widely used in clinical laboratories but is time-consuming, subjective, and prone to errors. METHODS: Deep learning models were trained using a dataset of 16,427 centrifuged blood images with known serum indices values (including hemolytic index, icteric index, and lipemic index) and their performance was evaluated by five-fold cross-validation. Models were developed for recognizing qualified, unqualified and image-interfered samples, predicting serum indices values, and finally composed into a deep learning-based system for the automatic assessment of serum quality. RESULTS: The area under the receiver operating characteristic curve (AUC) of the developed model for recognizing qualified, unqualified and image-interfered samples was 0.987, 0.983, and 0.999 respectively. As for subclassification of hemolysis, icterus, and lipemia, the AUCs were 0.989, 0.996, and 0.993. For serum indices and total bilirubin predictions, the Pearson's correlation coefficients (PCCs) of the developed model were 0.840, 0.963, 0.854, and 0.953 respectively. Moreover, 30.8% of serum indices tests were deemed unnecessary due to the preliminary application of the deep learning-based system. CONCLUSIONS: The deep learning-based system is suitable for the assessment of serum quality and holds the potential to be used as an accurate, efficient, and rarely interfered solution in clinical laboratories.

Development of a virtual classroom for pre-analytical phase of laboratory medicine for undergraduate medical students using the Delphi technique.

BACKGROUND: Amongst the pre-analytical, analytical, and post-analytical phase of laboratory testing, pre-analytical phase is the most error-prone. Knowledge gaps in understanding of pre-analytical factors are identified in the clinical years amongst undergraduate students due to lack of formal teaching modules on the pre-analytical phase. This study was conducted to seek experts' consensus in Clinical Chemistry on learning objectives and contents using the Delphi technique with an aim to develop an asynchronous virtual classroom for teaching pre-analytical factors of laboratory testing. METHODS: A mixed method study was conducted at the Aga Khan University. A questionnaire comprising of 16 learning objectives and their associated triggers was developed on Google Docs for developing the case vignettes. A four-point Likert Scale, which included strongly agree, agree, disagree and strongly disagree, was utilized for the learning objectives. An open-ended question was included for experts to suggest new items for inclusion. A cut off of at least 75% agreement was set to establish consensus on each item. A total of 17 Chemical Pathology faculty from 13 institutions across Pakistan were invited to participate in the first round of Delphi. Similar method of response was used in round two to establish consensus on the newly identified items suggested by the faculty in round 1. Later, the agreed-upon objectives and triggers were used to develop interactive scenarios over Moodle to concurrently test and teach medical students in a nonchalant manner. RESULTS: A total of 17 responses were received in Round 1 of the Delphi process (response rate = 100%), while 12 responses were received in Round 2 (response rate = 71%). In round 1, all 16 learning objectives reached the required consensus (≥ 75%) with no additional learning objectives suggested by the experts. Out of 75 triggers in round 1, 61 (81.3%) reached the consensus to be included while 39 were additionally suggested. In 2nd round, 17 out of 39 newly suggested triggers met the desired consensus. 14 triggers did not reach the consensus after two rounds, and were therefore eliminated. The virtual classroom developed using the agreed-upon learning objectives and triggers consisted of 20 items with a total score of 31 marks. The questions included multiple choice questions, fill in the blanks, drag and drop sequences and read-and-answer comprehensions. Specific learning points were included after each item and graphs and pictures were included for a vibrant experience. CONCLUSION: We developed an effective and interactive virtual session with expert consensus on the pre-analytical phase of laboratory testing for undergraduate medical students which can be used for medical technologist, graduate students and fellows in Chemical Pathology.

Types and Frequency of Errors in the Pre-Analytical Phase in the Clinical Laboratory - Single Center Study from Bosnia and Herzegovina.

BACKGROUND: The pre-analytical phase, which includes all preparatory actions to the analytical procedure, is part of the process during which there is the greatest possibility of laboratory errors. This study was conducted to investigate the frequency and types of laboratory errors during work in the clinical laboratory as well as the frequency and types of laboratory errors in the pre-analytical phase of laboratory work. METHODS: The retrospective, descriptive study covered the period from 01/01/2016 to 12/31/2016 within which the presence of 5 different indicators of quality of work, i.e., pre-analytical errors, was monitored: improperly drawn blood, coagulated blood sample, hemolyzed blood sample, improperly marked referral for analysis, and insufficient sample for analysis. RESULTS: The most common error in the pre-analytical phase of our study was "coagulated sample", followed by: "improperly drawn blood", "improperly marked referral", "insufficient sample for analysis", and "hemolyzed sample". Using the chi-squared test, a statistically significant difference was found in the frequency of occurrence of certain types of indicators in different departments (p < 0.005). CONCLUSIONS: Reduction of these errors can be achieved through analyzing and correcting the reasons for them, education, and by joint action of experts and international organizations, continual training of staff as well as to following the adopted guidelines and standards.

Pre-Analytical Error Cost Analysis of 10,732 Contaminated Urine Culture Samples.

BACKGROUND: Unlike other pre-analytical (PA) phase errors, in our country Social Security Institution (SSI) reimburses urine samples rejected due to contamination in the form of a finalized test. The primary purpose was to estimate the direct financial loss created by contaminated urine sampling. We want to encourage its prioritization among corrective and preventive actions of laboratory PA management. METHODS: We examined the urine samples which were sent to Istanbul Anatolian North Central Laboratory retrospectively. The central laboratory serves the community of 6,400-bed hospitals. We made direct financial loss calculations with material-, labor-, and waste-related financial elements. RESULTS: We rejected 10,732 of 138,834 samples due to contamination. With the 2019 Euro Index, the cost for each urine sample rejected due to contamination was calculated as € 2.98. CONCLUSIONS: It is the first cost study where the prices are in human resources, material, waste cost, and the amount reimbursed by SSI as direct cost elements per rejection sample. Highlighting the cost elements in establishing health policies predicted due to their striking feature may contribute to their prioritization in corrective and preventive actions. The urine culture test is the most commonly performed bacterial culture test. The determination of financial loss predicted that it would also reduce antibiotic resistance in healthcare by providing financial resource threshold information to develop improved methods. In addition, it will inspire new additions to the existing few detailed pre-analytical error cost studies.

Os principais erros da fase pré-analítica de exames laboratoriais / The main errors of the pre-analytical phase of laboratory exams

As análises clínicas laboratoriais possuem papel fundamental na saúde, pois é através de seus resultados que 70% dos diagnósticos são concluídos pelos médicos, e desta forma é necessário que se preze pela emissão de resultados confiáveis. Entretanto, uma das fases do processo de realização dos exames laboratoriais tem se destacado como a fase que concentra o maior percentual de erros no âmbito laboratorial até os dias atuais. Trata-se da fase pré-analítica, que se inicia com a solicitação do exame e finaliza quando se inicia a análise. Os erros pré-analíticos podem ser responsáveis por até 75% dos erros laboratoriais, o que mostra a vulnerabilidade desta fase. Portanto, este trabalho tem como objetivo identificar os principais erros que estão vinculados à fase pré-analítica, assim como os impactos que esses erros podem causar. Os tipos de erros pré-analíticos foram revisados na literatura entre os anos de 2011 a 2020. Os resultados apontaram que os principais erros pré-analíticos estão associados ao momento da coleta de amostras biológicas. Isto mostra a necessidade de gerar melhorias nos setores de coleta, através da realização de treinamentos voltados para as equipes de flebotomia, com o intuito de aperfeiçoar este processo e diminuir as taxas dos erros provocados nesta fase.

The clinical laboratory analyses have a fundamental role in health, because it is through their results that 70% of the diagnoses are concluded by the doctors, therefore, it is necessary to give priority to the issuance of reliable and safe results. However, one of the phases of the process of performing laboratory tests has been highlighted as the phase that concentrates the highest percentage of errors in the laboratory environment until the present day.It is the pre-analytical phase, which begins with the request of the exam and ends when the analysis begins.The pre-analytical errors can be responsible for up to 75% of laboratory errors, which shows the vulnerability of this phase. Therefore, this work aims to identify the main errors that are linked to the pre-analytical phase, as well as the impacts that these errors may cause. The types of pre-analytical errors were reviewed in the literature between 2011 and 2020. The results showed that the main pre-analytical errors are associated with the time of collection of biological samples. This shows the need to generate improvements in the collection sectors, through training for phlebotomy teams, in order to improve this process and decrease the rates of errors caused in this phase.

Making a science out of preanalytics: An analytical method to determine optimal tissue fixation in real-time.

Modern histopathology is built on the cornerstone principle of tissue fixation, however there are currently no analytical methods of detecting fixation and as a result, in clinical practice fixation is highly variable and a persistent source of error. We have previously shown that immersion in cold formalin followed by heated formalin is beneficial for preservation of histomorphology and have combined two-temperature fixation with ultra-sensitive acoustic monitoring technology that can actively detect formalin diffusing into a tissue. Here we expand on our previous work by developing a predictive statistical model to determine when a tissue is properly diffused based on the real-time acoustic signal. We trained the model based on the morphology and characteristic diffusion curves of 30 tonsil cores. To test our model, a set of 87 different tonsil samples were fixed with four different protocols: dynamic fixation according to our predictive algorithm (C/H:Dynamic, N = 18), gold-standard 24 hour room temperature (RT:24hr, N = 24), 6 hours in cold formalin followed by 1 hour in heated formalin (C/H:6+1, N = 21), and 2 hours in cold formalin followed by 1 hour in heated formalin (C/H:2+1, N = 24). Digital pathology analysis revealed that the C/H:Dynamic samples had FOXP3 staining that was spatially uniform and statistically equivalent to RT:24hr and C/H:6+1 fixation protocols. For comparison, the intentionally underfixed C/H:2+1 samples had significantly suppressed FOXP3 staining (p<0.002). Furthermore, our dynamic fixation protocol produced bcl-2 staining concordant with standard fixation techniques. The dynamically fixed samples were on average only submerged in cold formalin for 4.2 hours, representing a significant workflow improvement. We have successfully demonstrated a first-of-its-kind analytical method to assess the quality of fixation in real-time and have confirmed its performance with quantitative analysis of downstream staining. This innovative technology could be used to ensure high-quality and standardized staining as part of an expedited and fully documented preanalytical workflow.