Nora Nikolac

Preanalytical quality improvement: in quality we trust

Abstract Total quality in laboratory medicine should be defined as the guarantee that each activity throughout the total testing process is correctly performed, providing valuable medical decision-making and effective patient care. In the past decades, a 10-fold reduction in the analytical error rate has been achieved thanks to improvements in both reliability and standardization of analytical techniques, reagents, and instrumentation. Notable advances in information technology, quality control and quality assurance methods have also assured a valuable contribution for reducing diagnostic errors. Nevertheless, several lines of evidence still suggest that most errors in laboratory diagnostics fall outside the analytical phase, and the pre- and postanalytical steps have been found to be much more vulnerable. This collective paper, which is the logical continuum of the former already published in this journal 2 years ago, provides additional contribution to risk management in the preanalytical phase and is a synopsis of the lectures of the 2nd European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled “Preanalytical quality improvement: in quality we trust” (Zagreb, Croatia, 1–2 March 2013). The leading topics that will be discussed include quality indicators for preanalytical phase, phlebotomy practices for collection of blood gas analysis and pediatric samples, lipemia and blood collection tube interferences, preanalytical requirements of urinalysis, molecular biology hemostasis and platelet testing, as well as indications on best practices for safe blood collection. Auditing of the preanalytical phase by ISO assessors and external quality assessment for preanalytical phase are also discussed.

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

OBJECTIVES Our aim was to explore (i) the difference in concentration of IL-6, TNF-alpha and IL-10 between acute ischemic stroke patients and control individuals; (ii) the association of plasma cytokine concentration with stroke severity at admission assessed by NIHSS and stroke outcome in 90 days assessed by Barthel index (BI) and modified Rankin scale (mRS). MATERIALS AND METHODS Study included 68 stroke patients admitted within 12 h of symptoms onset and 71 controls. RESULTS IL-6 was increased in patients relative to controls (P=0.035) and this increase was associated with severe stroke (P=0.007) and worse outcome (P=0.030 and 0.019; assessed by BI and mRS, respectively), whereas IL-10 was decreased (P=0.044) and associated with better outcome (P=0.043). TNF-alpha did not differ between studied groups (P=0.302). CONCLUSIONS Increased IL-6 and reduced IL-10 concentrations are present in early stroke period and are associated with a degree of neurological deficit and/or stroke outcome.

Lipemia: causes, interference mechanisms, detection and management

In the clinical laboratory setting, interferences can be a significant source of laboratory errors with potential to cause serious harm for the patient. After hemolysis, lipemia is the most frequent endogenous interference that can influence results of various laboratory methods by several mechanisms. The most common preanalytical cause of lipemic samples is inadequate time of blood sampling after the meal or parenteral administration of synthetic lipid emulsions. Although the best way of detecting the degree of lipemia is measuring lipemic index on analytical platforms, laboratory experts should be aware of its problems, like false positive results and lack of standardization between manufacturers. Unlike for other interferences, lipemia can be removed and measurement can be done in a clear sample. However, a protocol for removing lipids from the sample has to be chosen carefully, since it is dependent on the analytes that have to be determined. Investigation of lipemia interference is an obligation of manufacturers of laboratory reagents; however, several literature findings report lack of verification of the declared data. Moreover, the acceptance criteria currently used by the most manufacturers are not based on biological variation and need to be revised. Written procedures for detection of lipemia, removing lipemia interference and reporting results from lipemic samples should be available to laboratory staff in order to standardize the procedure, reduce errors and increase patient safety.

Croatian Society of Medical Biochemistry and Laboratory Medicine : national recommendations for venous blood sampling

Phlebotomy is one of the most complex medical procedures in the diagnosis, management and treatment of patients in healthcare. Since laboratory test results are the basis for a large proportion (60–80%) of medical decisions, any error in the phlebotomy process could have serious consequences. In order to minimize the possibility of errors, phlebotomy procedures should be standardised, well-documented and written instructions should be available at every workstation. Croatia is one of the few European countries that have national guidelines for phlebotomy, besides the universally used CLSI (Clinical Laboratory Standards Institute) H3-A6 Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; approved Standard-Sixth Edition (CLSI, 2007) and WHO (World Health Organization) guidelines on drawing blood: best practices in phlebotomy (WHO, 2010). However, the growing body of evidence in importance of preanalytical phase management resulted in a need for evidence based revision and expansion of existing recommendations. The Croatian Society for Medical Biochemistry and Laboratory Medicine, Working Group for the Preanalytical Phase issued this recommendation. This document is based on the CLSI guideline H3-A6, with significant differences and additional information.

Comparison of visual vs. automated detection of lipemic, icteric and hemolyzed specimens: can we rely on a human eye?

Abstract Background: Results from hemolyzed, icteric, and lipemic samples may be inaccurate and can lead to medical errors. These preanalytical interferences may be detected using visual or automated assessment. Visual inspection is time consuming, highly subjective and not standardized. Our aim was to assess the comparability of automated spectrophotometric detection and visual inspection of lipemic, icteric and hemolyzed samples. Methods: This study was performed on 1727 routine biochemistry serum samples. Automated detection was performed using the Olympus AU2700 analyzer. We assessed: 1) comparability of visual and automated detection of lipemic, icteric and hemolyzed samples, 2) precision of automated detection, and 3) inter-observer variability for visual inspection. Results: Weighted κ coefficients for comparability of visual and automated detection were: 0.555, 0.529 and 0.638, for lipemic, icteric and hemolyzed samples, respectively. The precision for automated detection was high for all interferences, with the exception of samples being only slightly lipemic. The best overall agreement between observers was present in assessing lipemia (mean weighted κ=0.698), whereas the lowest degree of agreement was observed in assessing icterus (mean weighted κ=0.476). Conclusions: Visual inspection of lipemic, icteric and hemolyzed samples is highly unreliable and should be replaced by automated systems that report serum indices. Clin Chem Lab Med 2009;47:1361–5.

The prevalence of preanalytical errors in a Croatian ISO 15189 accredited laboratory.

Abstract Background: The preanalytical phase is the most common source of laboratory errors. The goal of this descriptive study was to analyze the prevalence and type of preanalytical errors in relation to the site of sample collection (inpatient vs. outpatient) and the type of laboratory unit (hematology and coagulation vs. biochemistry). For the biochemistry unit, the data were also analyzed relative to the type of the analysis (stat vs. routine). Methods: We retrospectively analyzed the sample and test request form error rate for a 1-year period, from January to December 2008. Results: The frequency of the sample errors differed significantly between the emergency and routine biochemistry unit (0.69% vs. 2.14%; p<0.0001), and between inpatients and outpatients (1.12% vs. 1.36%; p=0.0006). Hemolysis was the most frequent sample error, accounting for 65% of all unsuitable specimens in the emergency biochemistry unit. The total sample error rate did not differ between hematology and coagulation vs. the biochemistry unit. The frequency of test request form errors differed significantly with respect to the sample collection site (p<0.0001), laboratory unit (p<0.0001) and type of the analysis (p<0.0001). Errors in the test request form were least frequent in the outpatient unit (2.98%) and most frequent in the routine biochemistry unit (65.94%). Conclusions: Sample and test request form errors in our laboratory are occurring with a frequency comparable to that reported by others. Continuous educational action is needed for all stakeholders involved in laboratory testing to improve the quality of the preanalytical phase of the total testing process. Clin Chem Lab Med 2010;48:1009–14.

Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE)

Abstract Background: An observational study was conducted in 12 European countries by the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase (EFLM WG-PRE) to assess the level of compliance with the CLSI H3-A6 guidelines. Methods: A structured checklist including 29 items was created to assess the compliance of European phlebotomy procedures with the CLSI H3-A6 guideline. A risk occurrence chart of individual phlebotomy steps was created from the observed error frequency and severity of harm of each guideline key issue. The severity of errors occurring during phlebotomy was graded using the risk occurrence chart. Results: Twelve European countries participated with a median of 33 (18–36) audits per country, and a total of 336 audits. The median error rate for the total phlebotomy procedure was 26.9 % (10.6–43.8), indicating a low overall compliance with the recommended CLSI guideline. Patient identification and test tube labelling were identified as the key guideline issues with the highest combination of probability and potential risk of harm. Administrative staff did not adhere to patient identification procedures during phlebotomy, whereas physicians did not adhere to test tube labelling policy. Conclusions: The level of compliance of phlebotomy procedures with the CLSI H3-A6 guidelines in 12 European countries was found to be unacceptably low. The most critical steps in need of immediate attention in the investigated countries are patient identification and tube labelling.

The quality of the extra-analytical phase of laboratory practice in some developing European countries and Mexico - a multicentric study.

Abstract Background: This cross-sectional multicentric survey study aimed to assess the quality of the extra-analytical phase of laboratory activities in some developing European countries and Mexico. We assessed the quality of the extra-analytical practices in participating laboratories regarding the: a) sample acceptance criteria; b) phlebotomy procedures; c) test results reporting and d) recording non-conformities. Methods: A survey was performed during the April–May 2009. A total of 15 clinical laboratories from the following countries were included: Bosnia, Croatia, Czech Republic, Hungary, Mexico, Poland, Portugal, Romania, Serbia and Ukraine. Questions were scored (scores from 1–4) and average scores was calculated for each category. Results: The overall score for all respondents (n=443) was 3.10±0.33. The average score was 3.11±0.56 for sample acceptance criteria, 2.76±0.58 for phlebotomy and 3.34± 0.53, for test results reporting (F=116.49; p<0.001). Laboratory accreditation was associated with better practices and higher overall quality of the extra-analytical procedures (F=16.62; p<0.001). Moreover, the highest scores for sample acceptance criteria (F=8.32; p<0.001), phlebotomy procedures (F=13.28; p<0.001) and for reporting non-conformities (F=33.62; p<0.001) were observed for accredited laboratories or laboratories under preparation for accreditation. Conclusions: The overall quality of the extra-analytical practices in countries in this survey is not satisfactory. Phlebotomy practices are the most critical extra-analytical activity. Since laboratory accreditation was associated with better practices and higher overall quality of the extra-analytical procedures, we believe that the most significant improvement could be made by implementing the total quality management system and standardizing laboratory procedures.

Metabolic Control in Type 2 Diabetes Is Associated with Sulfonylurea Receptor-1 (SUR-1) but Not with KCNJ11 Polymorphisms

BACKGROUND AND AIMS Sulfonylureas are hypoglycemic agents used for promotion of insulin secretion in type 2 diabetics (T2D). They bind to sulfonylurea receptor-1 (SUR-1), which is a functional subunit of the ATP-sensitive potassium channel (K(ATP)). The other component of the potassium channel is Kir6.2, encoded by gene KCNJ11. Polymorphisms in these genes may lead to modulated response to sulfonylurea therapy. The aim of this study was to determine a relationship between SUR-1 [exon 16 (-3C/T), exon 31 (Arg1273Arg; AGG-->AGA) and exon 33 (S1369A)] and KCNJ11 (E23K) polymorphisms and the following parameters of metabolic control in T2D: fasting plasma glucose (FPG), postprandial glucose (PPG) and HbA1c in Caucasian T2D of European origin. METHODS A total of 228 unrelated patients with T2D on sulfonylurea therapy were included in the study. Genotyping of all polymorphisms was performed by PCR-RFLP method. Biochemical parameters were determined using standard laboratory methods. RESULTS There was no difference in FPG and PPG concentration in any of the genotype subgroups. However, diabetics with wild-type C/C genotype of the SUR-1 exon 16 polymorphism had significantly lower HbA1c concentration compared to the patients with variant T/T genotype [6.9 (6.2-7.7) mmol/L vs. 8.1 (6.7-8.8) mmol/L; p=0.009]. Also, patients with wild-type G/G genotype of the SUR-1 exon 31 polymorphism had significantly higher HbA1c concentration compared to the patients with variant A/A genotype [7.8 (6.9-8.8) mmol/L vs. 6.3 (5.7-6.8) mmol/L; p<0.001]. CONCLUSIONS SUR-1 exon 16 and exon 31 polymorphisms are significantly associated with HbA1c concentration.

How to assess the quality of your analytical method

Abstract Laboratory medicine is amongst the fastest growing fields in medicine, crucial in diagnosis, support of prevention and in the monitoring of disease for individual patients and for the evaluation of treatment for populations of patients. Therefore, high quality and safety in laboratory testing has a prominent role in high-quality healthcare. Applied knowledge and competencies of professionals in laboratory medicine increases the clinical value of laboratory results by decreasing laboratory errors, increasing appropriate utilization of tests, and increasing cost effectiveness. This collective paper provides insights into how to validate the laboratory assays and assess the quality of methods. It is a synopsis of the lectures at the 15th European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Continuing Postgraduate Course in Clinical Chemistry and Laboratory Medicine entitled “How to assess the quality of your method?” (Zagreb, Croatia, 24–25 October 2015). The leading topics to be discussed include who, what and when to do in validation/verification of methods, verification of imprecision and bias, verification of reference intervals, verification of qualitative test procedures, verification of blood collection systems, comparability of results among methods and analytical systems, limit of detection, limit of quantification and limit of decision, how to assess the measurement uncertainty, the optimal use of Internal Quality Control and External Quality Assessment data, Six Sigma metrics, performance specifications, as well as biological variation. This article, which continues the annual tradition of collective papers from the EFLM continuing postgraduate courses in clinical chemistry and laboratory medicine, aims to provide further contributions by discussing the quality of laboratory methods and measurements and, at the same time, to offer continuing professional development to the attendees.