Ana-Maria Simundic

Preanalytical quality improvement: from dream to reality

Abstract Laboratory diagnostics (i.e., the total testing process) develops conventionally through a virtual loop, originally referred to as “the brain to brain cycle” by George Lundberg. Throughout this complex cycle, there is an inherent possibility that a mistake might occur. According to reliable data, preanalytical errors still account for nearly 60%–70% of all problems occurring in laboratory diagnostics, most of them attributable to mishandling procedures during collection, handling, preparing or storing the specimens. Although most of these would be “intercepted” before inappropriate reactions are taken, in nearly one fifth of the cases they can produce inappropriate investigations and unjustifiable increase in costs, while generating inappropriate clinical decisions and causing some unfortunate circumstances. Several steps have already been undertaken to increase awareness and establish a governance of this frequently overlooked aspect of the total testing process. Standardization and monitoring preanalytical variables is of foremost importance and is associated with the most efficient and well-organized laboratories, resulting in reduced operational costs and increased revenues. As such, this article is aimed at providing readers with significant updates on the total quality management of the preanalytical phase to endeavour further improvement for patient safety throughout this phase of the total testing process.

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.

Harmonization of quality indicators in laboratory medicine. A preliminary consensus

Abstract Quality indicators (QIs) are fundamental tools for enabling users to quantify the quality of all operational processes by comparing it against a defined criterion. QIs data should be collected over time to identify, correct, and continuously monitor defects and improve performance and patient safety by identifying and implementing effective interventions. According to the international standard for medical laboratories accreditation, the laboratory shall establish and periodically review QIs to monitor and evaluate performance throughout critical aspects of pre-, intra-, and post-analytical processes. However, while some interesting programs on indicators in the total testing process have been developed in some countries, there is no consensus for the production of joint recommendations focusing on the adoption of universal QIs and common terminology in the total testing process. A preliminary agreement has been achieved in a Consensus Conference organized in Padua in 2013, after revising the model of quality indicators (MQI) developed by the Working Group on “Laboratory Errors and Patient Safety” of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The consensually accepted list of QIs, which takes into consideration both their importance and applicability, should be tested by all potentially interested clinical laboratories to identify further steps in the harmonization project.

Preanalytical phase – a continuous challenge for laboratory professionals

Preanalytical phase is the most vulnerable part of the total testing process and is considered to be among the greatest challenges to the laboratory professionals. However, preanalytical activities, management of unsuitable specimens and reporting policies are not fully standardized, nor harmonized worldwide. Several standards related to blood sampling and sample transportation and handling are available, but compliance to those guidelines is low, especially outside the laboratory and if blood sampling is done without the direct supervision of the laboratory staff. Furthermore, for some most critical procedures within the preanalytical phase, internationally accepted guidelines and recommendations as well as related quality measures are unfortunately unavailable. There is large heterogeneity in the criteria for sample rejection, the diff erent strategies by which unacceptable samples are managed, processed and test results reported worldwide. Management of unacceptable specimens warrants therefore immediate harmonization. Alongside the challenging and long road of patient safety, preanalytical phase off ers room for improvement, and Editors at Biochemia Medica Journal definitely hope to continue providing a respective mean for reporting studies on diff erent preanalytical phase topics. With pleasure and delight we invite potential future authors to submit their articles examining the quality of various preanalytical activities to Biochemia Medica. We will keep nurturing this topic as our prominent feature and by this we hope to be able to deliver valid evidence for some future guidelines and recommendations.

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.

Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease.

Abstract Although controversial, data on the genetic polymorphism of apoprotein E (APOE), methylenetetrahydrofolate (MTHFR) and paraoxonase (PON1) genes implicate their role in the development of cerebrovascular disease. The aim of this study was to assess the association of polymorphism of APOE, MTHFR and PON1 genes in 56 stroke and 36 carotid stenosis patients, and in 124 control subjects by PCR-restriction fragment length polymorphism analysis. In the stroke group a significantly different MTHFR genotype distribution (p=0.004, odds ratio for T/T of 17.571), but no significant difference in APOE and PON1 allele and genotype distribution compared to the control was found. The carotid stenosis group exhibited a significantly different APOE allele and genotype distribution (p=0.023, odds ratio APOE∊3∊4 of 4.24), but no significant difference in the MTHFR and PON1 allele and genotype distribution from the control group. The preliminary results obtained in this study revealed an association of the MTHFR and APOE gene polymorphism with cerebrovascular disease, suggesting a significant risk for stroke in subjects who are homozygous for the T allele and for carotid stenosis in subjects having APOE∊3∊4 genotype. Additional studies in larger patient groups are needed to confirm these observations.

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)

Abstract 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.

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.

Survey of national guidelines, education and training on phlebotomy in 28 European countries: an original report by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PA)

Abstract Background: European questionnaire survey was conducted by the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase (EFLM WG-PA) to assess how phlebotomy is performed in EFLM countries, including differences in personnel, level of education and skills, and to investigate the presence and compliance of national phlebotomy guidelines on this matter. Methods: A questionnaire was constructed containing questions elucidating different aspects of the organization behind the phlebotomy praxis on a national basis, including questions on the staff performing phlebotomy, the education of these staff members, and the existence of and adherence to national guidelines. All 39 EFLM member countries were invited to participate. Results: In total 28/39 (72%) EFLM member countries responded. Seven out of the 28 (25%) have national phlebotomy guidelines and five have implemented other guidelines. The estimated compliance with phlebotomy guidance for the laboratories in the countries that have national guidelines available is poor, regardless to whether the phlebotomy was under the laboratory control or not. Most countries were interested in EFLM guidelines and to participate in a pilot EFLM preanalytical phase external quality assessment (EQA) scheme. In the responding EFLM member countries, the majority of phlebotomy is performed by nurses and laboratory technicians. Their basic education is generally 4–5 years of high school, followed by 2–5 years of colleague or university studies. Only a third (10/28; 36%) of the participating member countries has any specific training available as a continuous educational resource. A specific training for phlebotomy is not part of the education required to become qualified in 6/28 (21%) and 9/28 (32%) of countries for nurses and laboratory technicians, respectively. In countries and professions where training is required, most require more than 5 h of training. Conclusions: Based on the results of this survey we conclude the following: 1) There is a need to assess the quality of current practices, compliance to the CLSI H3-A6 guidelines and to identify some most critical steps which occur during phlebotomy, in different healthcare settings, across Europe; 2) Existing CLSI H3-A6 phlebotomy guidelines should be adapted and used locally in all European countries which do not have their own guidelines; 3) National EFLM societies need to be engaged in basic training program development and continuous education of healthcare phlebotomy staff (implementing the certification of competence).