Ceftriaxone, a widely used antibiotic, is one of the most common drugs to cause drug-induced immune hemolytic anemia. In this report, we describe the effect of ceftriaxone on red blood cell parameters (low red blood cell count, low hematocrit, and high erythrocyte index values) in two pediatric patients without clinical symptoms of hemolytic anemia. Although automated hematology analyzers have helped to detect incorrect results, a peripheral blood smear examination was necessary for recognizing the erythrocyte agglutinins caused by ceftriaxone. Serological testing was not possible, but the resulting drug-induced antibodies mimicked cold agglutinins in the first patient and warm agglutinins in the second patient. Timely reactions and corresponding laboratory procedures prevented potential complications due to drug administration. This report aims to present laboratory findings and preanalytical challenges in these cases and share our experiences in solving them.

This case report investigates the occurrence of green discoloration in serum and citrate plasma samples collected from a male adult patient following a multivisceral organ transplant. In collected samples, it was necessary to investigate the influence of sample discoloration on the results of laboratory tests and to determine the appropriate approach to sample management. Hematology, coagulation and blood gas analysis showed no flags, but the biochemical lipemia index was susceptible to positive interference, necessitating dilution of the native sample. Despite the green discoloration, both native and diluted samples exhibited minimal interference on routine clinical chemistry analyses, demonstrating the reliability of the laboratory test results. This case report underscores the influence of preanalytical factors on the results of laboratory tests, the need for a thorough assessment of the sample adequacy for laboratory testing and the strict application of appropriate guidelines in the sample management in order to make an accurate diagnosis and ensure optimal patient care.

The application of advanced artificial intelligence (AI) models and algorithms in clinical laboratories is a new inevitable stage of development of laboratory medicine, since in the future, diagnostic and prognostic panels specific to certain diseases will be created from a large amount of laboratory data. Thanks to machine learning (ML), it is possible to analyze a large amount of structured numerical data as well as unstructured digitized images in the field of hematology, cytology and histopathology. Numerous researches refer to the testing of ML models for the purpose of screening various diseases, detecting damage to organ systems, diagnosing malignant diseases, longitudinal monitoring of various biomarkers that would enable predicting the outcome of each patient's treatment. The main advantages of advanced AI in the clinical laboratory are: faster diagnosis using diagnostic and prognostic algorithms, individualization of treatment plans, personalized medicine, better patient treatment outcomes, easier and more precise longitudinal monitoring of biomarkers, . Disadvantages relate to the lack of standardization, questionable quality of the entered data and their interpretability, potential over-reliance on technology, new financial investments, privacy concerns, ethical and legal aspects. Further integration of advanced AI will gradually take place on the basis of the knowledge of specialists in laboratory and clinical medicine, experts in information technology and biostatistics, as well as on the basis of evidence-based laboratory medicine. Clinical laboratories will be ready for the full and successful integration of advanced AI once a balance has been established between its potential and the resolution of existing obstacles.

Knowledge and systematic evaluation of analytical errors is the task of internal analytical quality control management. The aim of this study was to assess whether the Westgard rules proposed by Bio-Rad's Westgard Advisor software are more efficient in the monitoring of analytical performance than those previously in use.

Higher concentrations of the small-cell lung cancer (SCLC) serum marker, pro-gastrin-releasing peptide (proGRP), in lung inflammations has been indicated in literature. The objective of this study was to compare serum proGRP concentration in pneumonia, chronic obstructive pulmonary disease (COPD) and early-stage primary lung cancers.

Subclinical hypothyroidism (SCH) is an independent risk factor for cardiovascular diseases due to endothelial dysfunction and atherosclerosis development. The aim of this study was to determine whether the levothyroxine therapy could impact the concentrations of endothelial dysfunction blood markers, namely endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA) and endocan, in patients with a mild form of SCH (thyroid-stimulating hormone (TSH) ≤ 10 mIU/L).

Information about analyte stability is of crucial importance. The aims of this study were to determine the short- and long-term stability of synovial fluid calprotectin at various temperature conditions (4-8 °C for 7 days, - 20 °C and - 80 °C for 6 weeks).

The paper aims to present the case of an asymptomatic 22-year-old man who was referred to the hematologist by laboratory experts primarily due to the extreme elevation of the erythrocyte sedimentation rate with a value of 197 mm/h. Additionally, moderate changes in laboratory parameters such as hemoglobin, leukocytes, lactate dehydrogenase, C-reactive protein, fibrinogen, and beta-2-microglobulin were recorded. Upon extensive clinical workup that included laboratory, imaging, and histological methods, a diagnosis of primary pulmonary Hodgkin's lymphoma (PPHL) was established. Primary pulmonary Hodgkin's lymphoma is a rare malignant lymphoproliferative disease that exclusively affects the lungs, and so far, only about 100 cases worldwide have been reported. The patient underwent first-line systemic chemotherapy with chest radiation and complete remission was obtained. Two years after completion of the treatment, a relapsed PPHL was clinically confirmed. Second-line chemotherapy followed by high-dose systemic chemotherapy with autologous hematopoietic stem-cell transplantation was indicated which led to complete remission and continues after 10 years from the initial diagnosis. The case demonstrates the important role of laboratory medicine experts who instantly suspected the possible laboratory-related tumor pathology and referred the patient to further hemato-oncological evaluation. This contributed to the timely diagnosis of PPHL, administration of appropriate treatment, and favorable outcome.

Structural and functional alterations in platelets are an actual problem that requires more attention. The treatment of these illnesses proves challenging, inefficient and heavily relies on platelet donations. A difficult task confronting science is producing platelets , which calls for meticulous examination of factors affecting platelet generation. It is known that megakaryocytes produce platelets and differently: in the laboratory we can get a smaller number of platelets compared to the human body. This review primarily examines the stages of megakaryocyte maturation and the processes involved in platelet formation. The article reflects the results of both fundamental research on the problem and the new results obtained over the past decade. Currently, most scientists accept the pro-platelets theory of platelet formation. This review aims to explore in detail each stage of pro-platelet formation and the platelet formation process. It explains on the processes of polyploidization, endomitosis, and apoptosis, as well as the functions of structural cell components (microtubules, mitochondria, T- and α-granules) and pro-platelet migration. The microenvironment influence is acknowledged for the osteoblastic and vascular niches that affect thrombocytopoiesis. The additional aspect is the contribution of specific proteins to thrombocytopoiesis such as RhoA, β1-tubulin, cytokines IL-6, IL-8, Toll-like receptors, .

In highly stressed circumstances, such as COVID-19 pandemic, biomarkers of the vaccine-induced immunity could be especially convenient. The main aim of our study was to determine C-C motif ligand 20 (CCL20) concentration after Ad26.COV2.S vaccination in regard to more common proinflammatory molecules and its correlation with anti-SARS-CoV-2 antibody concentration. Secondly, we investigated inflammatory and immunologic profile differences between patients with and without arterial hypertension.

Ferroportin (Fpn) is the only known iron exporter and plays an essential role in iron homeostasis. Serum concentrations of Fpn in health and/or diseased states are still mostly unknown. Therefore, the aim of this study was to determine the concentration of Fpn in the serum of women of reproductive age (WRA) for the first time, and to establish whether there is a difference in the concentration of Fpn according to ferritin status.

Thyroid-stimulating hormone (TSH) is a glycoprotein secreted by the anterior pituitary gland and is regulated by negative feedback from the serum free thyroid hormones. In this study we aimed to quantitate the relative bias caused by calibration drifting as seen in our TSH Levey-Jennings quality control (QC) charts and assess the magnitude of bias on patients' samples.

Alkaptonuria is characterized by the accumulation of homogentisic acid which causes dark coloration of urine upon standing, ochronosis, and arthritis. A 4-year old child was referred to our pediatric nephrologist with hyperoxaluria and a history of unexplained pink-to-brown discolouration of his diapers associated with a brown-staining of clothes and skin since he was six months old. He had no other symptoms and his past medical history only included minor child illnesses. His 11-month-old brother had the same dark discoloration of his diapers. Laboratory testing on a spot urine sample showed hyperoxaluria and nephrotic range proteinuria with low creatinine and normal albumin concentrations. Considered causes were hyperoxaluria, alkaptonuria, interfering substance, adulteration. The further diagnostic work-up revealed increased homogentisic acid in urine, compatible with alkaptonuria. Urinary creatinine and total protein measurements on Roche Cobas were, respectively, falsely decreased and increased in the presence of homogentisic acid. The false-low creatinine resulted in an elevated oxalate/creatinine ratio. Alkaptonuria can cause a false increase of results expressed creatinine and should be excluded in case of an unexplained marked increase of urine total protein without a concomitant increase of albumin.

Pseudothrombocytopenia (PTCP) is defined by the occurence of spouriously low platelet count as a consequence of platelet aggregation. It is a rare and benign artifact, not associated with any specific disorder or therapy, that becomes clinically relevant when it is not timely and reliably recognized. Thus, it may result in inappropriate clinical decisions ( unnecessary further testing, misdiagnoses and potential patients' mismanagement) unavoidably compromising patient safety. The most common form of PTCP is caused by ethylenediaminetetraacetic acid (EDTA). Several approaches for the management of samples with EDTA-induced PTCP have been described in the literature. However, expert recommendations are scarce. The scope of these recommendations is to assist in achieving national harmonisation in laboratory management ( detecting and reporting platelet counts) of samples with EDTA-induced PTCP. These minimal recommendations were prepared by the members of the joint working group of the Croatian Chamber of Medical Biochemists and Working group for Laboratory Hematology of the Croatian Society of Medical Biochemistry and Laboratory Medicine, and might be customized according to specific conditions ( personnel and equipment) of each individual laboratory. These recommendations are primarily intended to all laboratory professionals involved in the management of samples with EDTA-induced PTCP, but also to other healthcare professionals involved in collecting samples and interpreting complete blood count results.

Laboratory medicine in sport and exercise has significantly developed during the last decades with the awareness that physical activity contributes to improved health status, and is present in monitoring both professional and recreational athletes. Training and competitions can modify concentrations of a variety of laboratory parameters, so the accurate laboratory data interpretation includes controlled and known preanalytical and analytical variables to prevent misleading interpretations. The paper represents a comprehensive summary of the lectures presented during the 35 Annual Symposium of the Croatian Society of Medical Biochemistry and Laboratory Medicine. It describes management of frequent sport injuries and sums up current knowledge of selected areas in laboratory medicine and sports including biological variation, changes in biochemical parameters and glycemic status. Additionally, the paper polemicizes sex hormone disorders in sports, encourages and comments research in recreational sports and laboratory medicine. In order to give the wider view, the connection of legal training protocols as well as monitoring prohibited substances in training is also considered through the eyes of laboratory medicine.

Adrenocorticotropic hormone (ACTH) is a peptide secreted by pituitary gland that plays an important role in regulating cortisol secretion. Its determination is difficult because of instability in whole blood. Several factors that influence ACTH stability in blood before analysis have been identified: temperature, hemolysis, time to centrifugation and presence of protease inhibitors. Published results on ACTH whole blood stability seem contradictory.

This study aimed to determine autoverification rules for routine glycated hemoglobin (HbA1c) analysis based on high-performance liquid chromatography (HPLC) principle. Laboratory information system (LIS) and Bio-Rad D-100 Advisor software (Bio-Rad, Hercules, USA) with graphics recognition function were carriers for the autoverification system.

Blue-green neutrophilic inclusions (BGNI), also known as "death bodies," are bright green structures observed in the cytoplasm of neutrophils or monocytes and are closely associated with acute liver failure, lactic acidosis, and other serious diseases. Some studies suggested a potential association with phagocytic lipofuscin released by damaged liver cells. The presence of BGNI typically indicated a poor prognosis. We presented two cases. Case 1 was diagnosed with novel bunyavirus infection and exhibited severe hepatic impairment and coagulation dysfunction along with the presence of BGNI in neutrophils. Despite receiving comprehensive symptomatic treatment, the patient's condition rapidly deteriorated leading to eventual demise. Case 2 had severe liver injury caused by wasp stings, and BGNI was observed. Following active treatment measures, the patient eventually achieved recovery. Throughout the disease course of case 1, there was a progressive deepening in color and increase in quantity of BGNI. Conversely, case 2 demonstrated an opposite trend. Based on the comparison of clinical outcomes and variations in color and quantity of BGNI between these two patients, it was found that an increase in the number and deepening of BGNI color corresponded to worsening condition. Conversely, a decrease in quantity and lightening of color indicated improvement. Hence, these findings suggest a possible association between changes in BGNI characteristics and prognosis.

Reliable and accurate measurement of blood glucose concentration is of crucial importance for making clinical decisions in diagnosis diabetes, gestational diabetes and impaired fasting glucose tolerance.

This case report describes interference from heterophilic antibodies in D-dimer assay. The interference was suspected due to discrepancies between D-dimer concentrations in the original sample and diluted samples, as well as inconsistent clinical findings. The patient's medical history, laboratory results, and imaging studies were considered in the investigation. Heterophilic antibodies, likely developed during the SARS-CoV-2 infection, were identified as the probable cause of interference. The interference was confirmed through various methods, including dilution studies, blocking heterophilic antibodies, and comparing results with an alternative D-dimer method. This case highlights the importance of recognizing and addressing interference in D-dimer testing, emphasizing the need for collaboration between clinicians and laboratory specialists.

Ovarian cancer is the 8th most common malignancy in women and the deadliest gynecological cancer. Due to the non-specific symptoms and the lack of effective diagnostic methods, late diagnosis remains the main barrier for improving the poor prognosis. Human epididymis protein 4 (HE4) is a protein overexpressed in ovarian cancer, but not in healthy individuals or benign conditions. The aim of this review article is to evaluate the laboratory aspect and potential clinical application of urine HE4. The methodology is presented, together with discussion on preanalytical, analytical and postanalytical phase of HE4 detection using urine. Moreover, we present the diagnostic role of urine HE4 in differential diagnosis, chemotherapy response, detection of recurrence and detection of low-malignant potential tumors. It has been found that urine HE4 presents as a promising, non-invasive tumor marker for detection and monitoring of ovarian cancer. However, standardization of the HE4 detection process is needed prior to implementation in clinical diagnostics.