Policies and practices in the field of laboratory hematology in Croatia - a current overview and call for improvement.

OBJECTIVES: In 2019 The Croatian Working Group for Laboratory Hematology, on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine, wanted to explore the background in field of laboratory hematology routine practice among Croatian laboratories in order to develop future strategies for producing national recommendations, if needed. METHODS: During April and May 2019, a comprehensive survey covering all main parts of the total testing process within the field of laboratory hematology among Croatian medical laboratories was conducted. The survey comprised 49 inquiries. Data was collected using Survey Monkey (Palo Alto, CA, USA). All collected data was anonymized. RESULTS: The response rate was 72%. There is still a substantial number of laboratories that have only three-part differential hematology analyzers (9%). Furthermore, a very high number of laboratories did not perform analyzer verification prior to implementation into routine work (31%). Out of those who have verified their analyzers, a diversity of guidelines and recommendations were used. Nearly 10% of the laboratories do not have a defined policy regarding specimen rejection. The majority of the participants perform internal quality control daily (83%), however, only 51% of respondents evaluate the agreement between different hematology analyzers on daily basis. Although more than 90% of Croatian laboratories have a defined policy regarding specimen rejection, only 61% of respondents continuously monitor quality indicators in routine practice. CONCLUSIONS: The survey revealed substantial differences in all aspects of laboratory hematology practices among Croatian medical laboratories, indicating the need for universal recommendations at the national level.

Platelet count, mean platelet volume and smoking status in stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), an increasing global health problem, may be complicated by acute atherothrombotic events. Although systemic inflammation plays the leading role in atherothrombotic processes, platelet activation and increased coagulation together with oxidative stress can significantly exacerbate atherosclerosis in COPD patients. In this study we determined platelet count, mean platelet volume (MPV) and classical markers of systemic inflammation - serum C-reactive protein (CRP), white blood cell (WBC) count and the relative proportion of segmented neutrophils in COPD patients, and compared them to those from the healthy controls. The most important and novel finding of this study was that patients with COPD had a significantly increased platelet count, along with a reduced MPV when compared to healthy controls (286 vs. 260 × 10(9)/l; 9.6 vs. 8.7 fL, respectively). Cigarette smoking had no influence on these results. The presence of systemic inflammation was clearly proved by the increase in classical inflammatory markers (CRP, WBC and segmented neutrophil count).

Glutathione cycle in stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidant/antioxidant imbalance. Glutathione is the most abundant cellular low-molecular weight thiol and the glutathione redox cycle is the fundamental component of the cellular antioxidant defence system. Concentration of total glutathione and catalytic activities of glutathione peroxidase and glutathione reductase were determined in peripheral blood of patients (n = 109) and healthy subjects (n = 51). Concentration of total glutathione in patients was not changed in comparison to healthy controls. However, we found statistically significant difference between patients with moderate and severe disease stages. Glutathione reductase activity was increased, while glutathione proxidase activity was decreased in the patients with COPD, when compared to healthy controls. We found no significant difference in glutathione peroxidase and glutathione reductase activities between stages. Patients who smoked had lower concentration of total glutathione compared with former smokers and never-smoking patients. Lung function parameters were inversely associated with glutathione level. Evidence is presented for differential modulation of glutathione peroxidase and glutathione reductase activities in peripheral blood of patients with stable COPD. We suppose that in addition to glutathione biosynthesis, glutathione reductase-dependent regulation of the glutathione redox state is vital for protection against oxidative stress.

Critical Results Reporting in Portuguese Hospital Laboratories: State-of-the-Art.

INTRODUCTION: This survey aimed to assess the state-of-the-art of current practices on critical results reporting among Portuguese Clinical Pathology Laboratories. The results of the survey will set basis for future standardization and national guideline development. MATERIALS AND METHODS: The survey was transmitted to 49 Clinical Pathology Laboratories among public hospitals inserted in the Portuguese National Health System. In 27 questions, laboratories were asked about their critical results procedures, critical results list, reporting and further education. Data were analyzed using Microsoft Excel v.2016 and MedCalc Statistical Software version 12.5.0.0 (Ostend, Belgium). Where applicable, the comparison of proportions was used to estimate the level of significance (P<0.05). RESULTS: The response rate was 44/49 (90%), including 36 participants with a defined critical results reporting procedure. Among them, 31 laboratories defined a critical results list, mainly based on published literature (27/31). There was a statistically significant number of laboratories (P=0.019, 24/30) that report different critical results depending on the patient's age, but regardless of disease, ethnicity and location (P>0.05). The majority of laboratories (60%) report critical results via telephone within 15 minutes. Critical results are usually reported by clinical pathologists to physicians. Twenty-five laboratories periodically reevaluate their critical results list. CONCLUSION: Despite the fact that most of the Portuguese hospitals have a critical results policy, this survey showed high variability among the hospitals concerning critical results reporting practices and critical results list. This survey points out that nationally established procedures and guidelines are urgent step for critical results standardization.

Analytical verification and quality assessment of the Tosoh HLC-723GX HbA1c analyzer.

OBJECTIVES: Ion-exchange high-performance liquid chromatography (IE-HPLC) has long been used as a reproducible and versatile analytical tool for HbA1c measurement. In this study, we performed analytical verification and quality assessment of the recently introduced small IE-HPLC Tosoh HLC-723GX HbA1c analyzer, and a comparison of results to immunoassay (IA) and capillary electrophoresis (CE). DESIGN AND METHODS: The total imprecision of Tosoh HLC-723GX was verified according to CLSI EP15-A2 protocol using commercial control materials (C-QC) and pooled human whole blood samples (HWB). The Sigma metric was used for the evaluation of quality targets. HbA1c results were compared to automated CE (MiniCap Flex Piercing, Sebia, France) and IA (Tina-quant HbA1c Gen 2, Cobas Integra 400+, Roche Diagnostics, USA) procedures. RESULTS: The total imprecision of Tosoh HLC-723GX-HbA1c for IFCC(mmol/mol) and NGSP(%) units was: 1.91/1.25% (HbA1c=31 mmol/mol/5.0%) and 0.51/0.63% (HbA1c=84 mmol/mol/9.8%) for C-QC, and 0.39/0.2% (HbA1c=47 mmol/mol/6.5%) and 0.77/0.46% (HbA1c=94 mmol/mol/10.8%) in HWB samples, respectively. Bland-Altman analysis did not reveal any deviation of the results between Tosoh HLC-723GX and CE: mean difference 0.0% (95%CI: -0.02927 to 0.02653%), while the mean HbA1c difference against IA was -0.07% (95%CI: -0.1039 to -0.02765). At the selected HbA1c clinical decision level (48 mmol/mol/6,5%), six sigma analysis gave σ value of 3.91, within a desirable classification of performance. CONCLUSION: The analytical performance of the Tosoh HLC-723GX complies with the rigorous quality criteria for clinical use of HbA1c, with the results comparable to the CE procedure. Tosoh HLC-723GX provides a plausible analytical choice for reliable HbA1c measurement in low-volume laboratories.

The role of laboratory testing in detection and classification of chronic kidney disease: national recommendations.

Chronic kidney disease (CKD) is a common clinical condition with significant adverse consequences for the patient and it is recognized as a significant public health problem. The role of laboratory medicine in diagnosis and management of CKD is of great importance: the diagnosis and staging are based on estimation of glomerular filtration rate (eGFR) and assessment of albuminuria (or proteinuria). Therefore, the joint working group of the Croatian society of medical biochemistry and laboratory medicine and Croatian chamber of medical biochemists for laboratory diagnostics in CKD issued this national recommendation regarding laboratory diagnostics of CKD.Key factors for laboratories implementing the national guidelines for the diagnosis and management of CKD are:1. Ensure good communication between laboratory professionals and clinicians, such as nephrologists or specialists in general/family medicine,2. Ensure all patients are provided with the same availability of laboratory diagnostics,3. Ensure creatinine assays are traceable to isotope dilution mass spectrometry (IDMS) method and have minimal bias and acceptable imprecision,4. Select the appropriate GFR estimating formula. Recommended equation is the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD - EPI) equation,5. In reporting the key laboratory tests (creatinine, eGFR, urine albumin-to-creatinine ratio, urine protein-to-creatinine ratio) use the appropriate reporting units,6. Provide adequate information on limitations of creatinine measurement.The manuscript has been organized to identify critical points in laboratory tests used in basic laboratory diagnostics of CKD and is based on the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.

A Pathway to National Guidelines for Laboratory Diagnostics of Chronic Kidney Disease - Examples from Diverse European Countries.

The principal benefit of guidelines is to improve the quality of care received by patients. In the 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (KDIGO) was released and it is designed to provide information and assist decision making. This review gives a brief overview of a various national CKD guidelines that rely on the newly released KDIGO guidelines. All of the included countries (France, Turkey, Norway and Croatia) are non-English speaking countries and they differ in population and socio economic aspects. Examples shown in this review may provide valuable experience for countries that are in process of creating their national CKD guidelines.

Impact of creatinine methodology on glomerular filtration rate estimation in diabetes.

AIM: To evaluate the influence of creatinine methodology on the performance of chronic kidney disease (CKD)-Epidemiology Collaboration Group-calculated estimated glomerular filtration rate (CKD-EPI-eGFR) for CKD diagnosis/staging in a large cohort of diabetic patients. METHODS: Fasting blood samples were taken from diabetic patients attending our clinic for their regular annual examination, including laboratory measurement of serum creatinine and eGFR. RESULTS: Our results indicated an overall excellent agreement in CKD staging (kappa = 0.918) between the Jaffé serum creatinine- and enzymatic serum creatinine-based CKD-EPI-eGFR, with 9% of discordant cases. As compared to the enzymatic creatinine, the majority of discordances (8%) were positive, i.e., associated with the more advanced CKD stage re-classification, whereas only 1% of cases were negatively discordant if Jaffé creatinine was used for eGFR calculation. A minor proportion of the discordant cases (3.5%) were re-classified into clinically relevant CKD stage indicating mildly to moderately decreased kidney function (< 60 mL/min per 1.73 m2). Significant acute and chronic hyperglycaemia, assessed as plasma glucose and HbA1c levels far above the recommended glycaemic goals, was associated with positively discordant cases. Due to a very low frequency, positive discordance is not likely to present a great burden for the health-care providers, while intensified medical care may actually be beneficial for the small number of discordant patients. On the other hand, a very low proportion of negatively discordant cases (1%) at the 60 mL/min per 1.73 m2 eGFR level indicate a negligible possibility to miss the CKD diagnosis, which could be the most prominent clinical problem affecting patient care, considering high risk of CKD for adverse patient outcomes. CONCLUSION: This study indicate that compensated Jaffé creatinine procedure, in spite of the glucose-dependent bias, is not inferior to enzymatic creatinine in CKD diagnosis/staging and therefore may provide a reliable and cost-effective tool for the renal function assessment in diabetic patients.

A Summary of Worldwide National Activities in Chronic Kidney Disease (CKD) Testing.

Chronic kidney disease (CKD) is a major public health issue worldwide and is associated with adverse health outcomes, especially in low- and middle-income countries. In a cash limited healthcare system, guidelines that improve the efficiency of health care free up resources needed for other healthcare services. This short review presents some examples from national acitivities in CKD testing, including countries throughout the globe: Mexico in North America, Uruguay in South America, Italy in Europe, Nigeria in Africa and India in Asia. Considering the fact that treatment of CKD is cost-effective and improves outcomes, this observation argue in favor of including CKD in national guidelines and noncommunicable chronic disease (NCD) programs. This diverse example of national activities fullfil the very first step in achieving this goal.

Hemolysis from a nurses' standpoint--survey from four Croatian hospitals.

INTRODUCTION: Hemolysis can occur during sample collection, handling and transport. It is more frequent when the non-laboratory staff performs sampling. The aim of this study was to assess nurses' knowledge on the causes of hemolysis and consequential impact on the laboratory tests results. Additionally, the differences in knowledge, related to work experience, professional degree and previous education about hemolysis were explored. MATERIALS AND METHODS: An anonymus survey, containing 11 questions on demographics, causes of hemolysis, its impact on biochemical parameters and nurses' attitude towards additional education in preanalytics, was conducted in four Croatian hospitals. The answers were compared by Chi-squared and Fischer exact test. RESULTS: In total, 562 survey results were collected. Majority of nurses declared familiarity with the term "hemolysis" (99.6%). There were 77% of correct answers regarding questions about the causes of hemolysis, but only 50% when it comes to questions about interference in biochemical tests. The percentage of correct answers about causes was significantly lower (P=0.029) among more experienced nurses, and higher (P=0.027) in those with higher professional degree, while influence of previous education was not significant. Also, higher percentage of correct answers about interferences was encountered in nurses with longer work experience (P=0.039). More than 70% of nurses declared that additional education about preanalytical factors would be beneficial. CONCLUSION: Croatian nurses are familiar with the definition of hemolysis, but a lack of knowledge about causes and influence on laboratory test results is evident. Nurses are eager to improve their knowledge in this field of preanalytical phase.

Laboratory diagnostics of chronic kidney disease in Croatia: state of the art.

INTRODUCTION: Early identification and management of chronic kidney disease (CKD) is highly cost-effective and can reduce the risk of kidney failure progression and cardiovascular disease. In 2014, the Joint Croatian Working Group (JCWG) for laboratory diagnostic of CKD on the behalf of Croatian society of medical biochemistry and laboratory medicine (CSMBLM) and Croatian chamber of medical biochemists (CCMB) conducted a survey across Croatian medical-biochemistry laboratories to assess the current practice in this area of laboratory medicine. The aim of this study was to present the data collected through the survey and to give insight about laboratory diagnostics of chronic kidney disease in Croatia. MATERIALS AND METHODS: An invitation to participate in the survey was sent to all Croatian medical-biochemistry laboratories (N=196). The questionnaire was designed in a form of questions and statements, with possible multiple answers, comprising 24 questions. RESULTS: The response rate was 80/196 (40.8%). 39 answers were from primary medical-biochemistry laboratories. 31/78 (0.40) laboratories measure creatinine with non-standardized method (uncompensated Jaffe method). 58/78 (0.74) of laboratories that measure creatinine do not report eGFR values. Similar number of laboratories (58/80, 0.73) do not measure urine albumin or protein. CONCLUSIONS: There is a large heterogeneity among Croatian laboratories regarding measuring methods, reporting units and reference intervals (cut-off values), both for creatinine and urine albumin or protein. The two key prerequisites for CKD screening, automatic reporting of eGFR and albuminuria or proteinuria assessment, are not implemented nationwide. There is a need for harmonization in laboratory diagnostics of CKD in Croatia.

Validation of a laboratory and hospital information system in a medical laboratory accredited according to ISO 15189.

INTRODUCTION: The aim of the study was to present a protocol for laboratory information system (LIS) and hospital information system (HIS) validation at the Institute of Clinical Chemistry and Laboratory Medicine of the Merkur University Hospital, Zagreb, Croatia. MATERIALS AND METHODS: Validity of data traceability was checked by entering all test requests for virtual patient into HIS/LIS and printing corresponding barcoded labels that provided laboratory analyzers with the information on requested tests. The original printouts of the test results from laboratory analyzer(s) were compared with the data obtained from LIS and entered into the provided template. Transfer of data from LIS to HIS was examined by requesting all tests in HIS and creating real data in a finding generated in LIS. Data obtained from LIS and HIS were entered into a corresponding template. The main outcome measure was the accuracy of transfer obtained from laboratory analyzers and results transferred from LIS and HIS expressed as percentage (%). RESULTS: The accuracy of data transfer from laboratory analyzers to LIS was 99.5% and of that from LIS to HIS 100%. CONCLUSION: We presented our established validation protocol for laboratory information system and demonstrated that a system meets its intended purpose.