The band count imprecision - a Croatian multicentric pilot study.

Introduction: Due to high inter-observer variability the 2015 International Council for Standardization in Haematology (ICSH) recommendations state to count band neutrophils as segmented neutrophils in the white blood cell (WBC) differential. However, the inclusion of bands as a separate cell entity within the WBC differential is still widely used in hematology laboratories in Croatia. The aim of this multicentric study was to assess the degree of inter-observer variability in enumerating band neutrophils within the WBC differential among Croatian laboratories. Materials and methods: Seven large Croatian hospital laboratories from different parts of the country participated in the study. In each of 7 participating laboratories, one blood smear, that was flagged by the analyzer as possibly having bands, was evaluated by all personnel participating in the analysis of hematology samples. Between-observer manual smear reproducibility was expressed as coefficient of variation (CV) and calculated using the following formula: CV (%) = (standard deviation (SD)/mean value) x 100%. Results: The CVs (%) and relative band neutrophil counts in participating laboratories were as follows: 15.4% (16-24), 19.2% (16-32), 19.5% (17-40), 21.1% (17-44), 35.0% (8-26), 51.9% (3-29), and remarkably high 62.4% (12-59). For segmented neutrophils CVs were lower, ranging from 7.4% to 32.2%. The CVs did not correlate with the number of staff members in each hospital (P = 0.293). Conclusions: This study revealed very high variability in enumerating band neutrophil count in the blood smear differential among all participants, thus prompting a need for action on a national level.

Plasma Drug Values of DOACs in Patients Presenting with Gastrointestinal Bleeding: A Prospective Observational Study.

Background and Objectives: Anticoagulants are a well-known risk factor for gastrointestinal bleeding (GIB). In recent years, direct oral anticoagulants (DOACs) have taken a leading role in the treatment and prevention of thromboembolic incidents. The aim of this study was to investigate the prevalence of DOAC-treated patients with GIB whose plasma drug concentrations exceeded the cut-off values reported in the literature and to evaluate their clinical characteristics. Materials and Methods: Patients who were admitted to the Intensive Care Unit in the period 2/2020-3/2022 due to GIB were prospectively included in the study and classified into three groups according to the prescribed type of DOAC (apixaban, rivaroxaban, and dabigatran). For all participants, it was determined if the measured plasma drug levels exceeded the maximum serum concentration (Cmax) or trough serum concentration (Ctrough) obtained from the available data. A comparison of clinical parameters between the patients with and without excess drug values was performed. Results: There were 90 patients (54.4% men) included in the study, of whom 27 were treated with dabigatran, 24 with apixaban, and 39 with rivaroxaban. According to Cmax, there were 34 (37.8%), and according to Ctrough, there were 28 (31.1%) patients with excess plasma drug values. A statistically significant difference regarding excess plasma drug values was demonstrated between DOACs according to both Cmax (p = 0.048) and Ctrough (p < 0.001), with the highest rate in the group treated with dabigatran (55.6% for Cmax and 59.3% for Ctrough). Multivariate logistic regression showed that age (OR 1.177, p = 0.049) is a significant positive and glomerular filtration rate (OR 0.909, p = 0.016) is a negative predictive factor for excess plasma drug values. A total of six (6.7%) patients had fatal outcomes. Conclusions: Plasma drug concentrations exceed cut-off values reported in the literature in more than one-third of patients with GIB taking DOAC, with the highest rate in the dabigatran group. Clinicians should be more judicious when prescribing dabigatran to the elderly and patients with renal failure. In these patients, dose adjustment, plasma drug monitoring, or substitution with other, more appropriate DOACs should be considered.

Laboratory medicine in pandemic of COVID-19.

After the outbreak in China in the year 2019, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) quickly spread around the world causing a protracted pandemic. Approximately one-third of infections appear to be asymptomatic. Symptomatic disease is characterized primarily by symptoms of respiratory tract infection of varying severity. But Coronavirus Disease 2019 (COVID-19) is much more than an acute respiratory disease because SARS-CoV-2 affects many organs inducing a vast number of symptoms such as cardiovascular, neurological, gastrointestinal, dermatological, with numerous complications. Short and long-term effects of infection, severe ones, and especially mild forms of the disease which affect a huge number of patients need to be further investigated. Laboratory medicine has a crucial role in early diagnosis of the disease, recognition of the patients who need hospital care, and close monitoring of hospitalized patients to timely identify associated clinical complications as well as follow-up of patients with long-term COVID-19.

Reporting of activated partial thromboplastin time (aPTT): Could we achieve better comparability of the results?

INTRODUCTION: Activated partial thromboplastin time (aPTT) is determined and reported as clotting time in seconds aPTT(s), but it is presumed that reporting results as patient-to-normal clotting time ratio, aPTT(r), could minimize within-laboratory variability. The aim of study was to investigate differences in reporting aPTT results that can affect comparability of the results among Croatian laboratories and suggest further steps for its harmonization. MATERIALS AND METHODS: The questionnaire on aPTT reporting practice was distributed to 83 laboratories through Survey Monkey application in March 2019 as the part of the first regular round of Croatian Centre for Quality Assessment in Laboratory Medicine proficiency testing. RESULTS: The survey response rate was 0.49. Majority of laboratories report aPTT results as both, seconds and ratio. Participants reported use of 23 different aPTT(s) reference intervals along with 17 different combinations of reagent/coagulometer and 25 aPTT(s) denominators of different origin for aPTT(r) calculation. Despite the same aPTT(s) results, the use of different denominators caused a dispersion of aPTT(r) results that can lead to exceeding external quality assessment performance criteria of 7%, particularly when results were compared for the same reagent group only. By applying aPTT(s) reference interval mean as denominator for calculation of aPTT(r) reference interval better concordance to harmonized one was obtained (17 vs. 27; χ2 = 3.972; P = 0.046). CONCLUSION: In order to improve comparability of the results, laboratories are advised to use mean of aPTT(s) reference interval as denominator for aPTT(r) calculation. Type of coagulometer need to be considered when evaluating aPTT proficiency test results and its currently acceptable limit of performance evaluated accordingly.

How well do Croatian laboratories adhere to national recommendations for laboratory diagnostics of chronic kidney disease (CKD)?

Background In 2014, the Joint Croatian Working Group (JCWG) for laboratory diagnostic of chronic kidney disease (CKD) conducted a survey across medical-biochemistry laboratories which demonstrated a large heterogeneity in this area of laboratory medicine. To ensure the tools for the standardization process, in 2017 the JCWG-CKD published the first Croatian recommendations for laboratory diagnostics of CKD. To assess the implementation process, we have repeated a survey to explore how well laboratories adhere to the recommendations. Methods An invitation to the survey was sent to all Croatian medical-biochemistry laboratories (n = 196). The questionnaire was designed in a form of 19 questions and statements, with possible multiple answers. Results The response rate was 98/196 (50.0%). The predominant method for serum creatinine measurement was the standardized compensated Jaffe method (79.2%). There was substantial decrease in the number of laboratories which measure creatinine with the non-standardized uncompensated Jaffe method, compared with the initial 2014 assessment; 7% vs. 40%, respectively. The number of the laboratories that did not report estimated glomerular filtration rate (eGFR) values decreased almost by half compared to the initial data (37.6% vs. 74.4%). However, compared to the 2014 initial assessment, a similar number of laboratories (54/98 vs. 58/80) did not measure urine albumin or protein. Conclusions The collected data showed a substantial improvement in the standardization of the serum creatinine measurement, as well as in the reporting of eGFR. However, albuminuria or proteinuria assessment is still not implemented nationwide, mainly in primary health care laboratories. This demonstrates the importance of promoting and monitoring implementation of guidelines after publication.

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.