Ann Clin Biochem
· 2026 May · PMID 40955084
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BackgroundZinc deficiency is a global concern, particularly in low-income countries, but also among vulnerable groups in Western countries, such as children. Diagnosing mild or moderate zinc deficiency is however challen...BackgroundZinc deficiency is a global concern, particularly in low-income countries, but also among vulnerable groups in Western countries, such as children. Diagnosing mild or moderate zinc deficiency is however challenging because of nonspecific symptoms and due to circulating zinc showing only subtle changes, requiring high accuracy in measurement. Challenges to accurate measurement include variations from choice of analytical instrument, analysis performance, and preanalytical factors such as choice of sample matrices and delayed blood sample processing. This study aimed to examine the stability of zinc in plasma and serum, measured by the recommended inductively coupled plasma optical emission spectrometry (ICP-OES) method and a direct colourimetric assay on the fully automated Roche Cobas c702 analyzer.MethodsA total of 245 whole blood samples were stored at room temperature for 0-8 h after blood sampling, then centrifuged for 10 min at 2000 g (serum) or 5 min at 2650 g (plasma), frozen at -20°C, and analysed, respectively, on ICP-OES and Cobas, the latter with the colourimetric kit from Sentinel diagnostics.ResultsSerum zinc concentrations measured on Cobas and ICP-OES showed no statistically significant change up to 6 h and never exceeded acceptable limits. Plasma zinc concentrations increased steadily over time, exceeding acceptable limits after 6 h. There were statistically significant differences between zinc measurements on ICP-OES and Cobas in both serum and plasma.ConclusionsZinc is stable for at least 8 h in serum and up to 6 h in plasma when measured by either Sentinel diagnostic colourimetric method on Cobas or ICP-OES.
Ann Clin Biochem
· 2026 May · PMID 40954105
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BackgroundMultiple myeloma patients may present with spuriously elevated serum phosphate levels resulting from the presence of paraproteins interfering in the phosphomolybdate UV assay. If this phenomenon is not recogniz...BackgroundMultiple myeloma patients may present with spuriously elevated serum phosphate levels resulting from the presence of paraproteins interfering in the phosphomolybdate UV assay. If this phenomenon is not recognized, patients possibly receive unnecessary treatments. This short report highlights the existence of paraprotein-related pseudohyperphosphatemia, and aims to provide accessible solutions to eliminate this interference.Material and MethodsIn a patient known with IgG multiple myeloma and unexplained hyperphosphatemia, the correlation between serum phosphate levels (phosphomolybdate UV assay) and IgG concentrations (immunoturbidimetry) was evaluated. To investigate the effect of the paraprotein on phosphate levels, phosphate was measured in one serum sample before and after protein removal by either dilution, protein precipitation with sulfosalicylic acid or zinc sulphate, or ultrafiltration.ResultsA patient with multiple myeloma presented with an unexplained hyperphosphatemia which correlated positively with serum IgG concentrations. As serum dilution normalized the phosphate level, it was hypothesized that precipitation of the paraprotein during the assay reaction interfered with the measurement and resulted in pseudohyperphosphatemia. Protein removal by precipitation with sulfosalicylic acid or zinc sulphate efficiently reduced the IgG level below the detection limit but did not result in a reliable phosphate measurement. Successful removal of proteins and a serum phosphate level that matched the patient's other biochemistry parameters and clinical condition were obtained by ultrafiltration.ConclusionParaproteins can interfere with the reaction components in the phosphomolybdate UV assay and result in pseudohyperphosphatemia. If the presence of this phenomenon is established, a reliable phosphate concentration can be obtained after ultrafiltration of the sample.
Premadasa T, Samarathunga E, Sujith EM
… +4 more, Shameela N, Basnayaka B, Antonypillai CN, Jayawardana R
Ann Clin Biochem
· 2026 May · PMID 40954102
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IntroductionShort Synacthen Test (SST), a standard diagnostic test to confirm Adrenal insufficiency (AI), involves substantial expenses.ObjectivesThis study aimed to assess the predictive value of baseline Cortisol level...IntroductionShort Synacthen Test (SST), a standard diagnostic test to confirm Adrenal insufficiency (AI), involves substantial expenses.ObjectivesThis study aimed to assess the predictive value of baseline Cortisol levels for SST outcomes and establish baseline cut-off levels for confirming AI to minimize the necessity of SST.MethodsAll SST data from 2019 to 2024 at National Hospital Kandy, Sri Lanka, were obtained retrospectively. A peak Cortisol ≥500 nmol/L at 30 or 60-min post-SST was considered as a normal adrenal reserve, whereas failure indicated AI. Pearson's correlation and Logistic Regression analysis assessed baseline and post-SST Cortisol at 30 and 60-min. A 2 × 2 table assesses test agreement. Receiver operating characteristic (ROC) curve analysis evaluated the SST outcomes at 30 and 60-min separately assessing sensitivity, specificity, and area under the curve (AUC).ResultsA total of 307 patients were enrolled, and 63.19% exhibited a failed SST response. Baseline Cortisol positively correlated with post-SST Cortisol at 30-min (r = 0.74, < .05) and 60-min (r = 0.68, < .05) with a good AUC for both 30 min (AUC = 0.855) and 60 min (AUC = 0.829). Baseline Cortisol demonstrated the higher odds ratio per unit (OR = 1.015 per nmol/L), indicating greater sensitivity to small changes. ROC curves were utilized to derive cut-offs for baseline Cortisol levels predicting SST outcomes. At 30-min, baseline Cortisol <135 nmol/L suggests AI (100% sensitivity, 44% specificity), and >381.5 nmol/L indicates normal adrenal reserve (100% specificity, 21.8% sensitivity). Similarly at 60-min, baseline Cortisol <75.3 nmol/L suggests AI (100% sensitivity, 19.7% specificity), and >357 nmol/L indicates normal adrenal reserve (100% specificity, 16.8% sensitivity).ConclusionsApplying these cut-offs could avoid 41.69% (30 min) or 19% (60 min) of total SSTs, excluding AI and normal adrenal reserve. 30-min SST Cortisol correlates more strongly with baseline Cortisol, showing a higher r-value, higher OR and AUC. Hence, 30-min provides better cut-offs with higher sensitivity and specificity minimizing need for SST. Patients with baseline Cortisol between 135 and 381 nmol/L can undergo SST with only a 30-min Cortisol measurement.
Jinda P, Kitpoka P, Thienphopirak W
… +10 more, Chiawchan S, Prommas S, Sukprasong R, Rachanakul J, Wiwattanakul S, Suteerojntrakool O, Bongsebandhu-Phubhakdi C, Tempark T, Hunthai S, Puangpetch A
Ann Clin Biochem
· 2026 May · PMID 40919916
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BackgroundThiopurine S-methyltransferase (TPMT) is crucial for metabolizing thiopurine drugs. This study aimed to establish the cutoff values for TPMT activity in a cohort of healthy individuals. We defined normal TPMT a...BackgroundThiopurine S-methyltransferase (TPMT) is crucial for metabolizing thiopurine drugs. This study aimed to establish the cutoff values for TPMT activity in a cohort of healthy individuals. We defined normal TPMT activity ranges and identified clinically applicable thresholds to distinguish individuals with normal TPMT function from those with reduced or deficient activity.MethodsA total of 457 participants, including 207 children and 250 healthy adults without prior thiopurine drug exposure, were enrolled. TPMT activity was measured and common defective genetic variants ( and ) were detected. To determine TPMT activity cutoff values and maximize sensitivity and specificity, receiver operating characteristic curve analysis was employed.ResultsThe cutoff values for TPMT activity in children were ≥52.9 nmol 6-MMP/g Hb/h for persons of the wild type and <52.9 nmol 6-MMP/g Hb/h for individuals who were heterozygous. In adults, the cutoff values were ≥44.6, 31.58-44.5, and <31.58 nmol 6-MMP/g Hb/h for wild-type, heterozygous, and compound heterozygous individuals, respectively. The sensitivity and specificity were 79.29% and 100% in children, whereas, in adults, they were 61.86% and 78.57%, 38.46% and 64.73%, and 100% and 95.98% in the wild-type, heterozygous, and compound heterozygous, respectively.ConclusionsIdentifying TPMT activity cutoff values is crucial for managing patients receiving thiopurine therapy, especially in Thailand. This approach allows for personalized treatment plans and minimizes the risk of adverse drug reactions. Since TPMT activity cutoff values can differ by population and testing methods, it is important to establish specific cutoff values locally.
Hatherley J, Collinson P, Shantsila E
… +2 more, Gaze D, Khand A
Ann Clin Biochem
· 2026 May · PMID 40877034
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Myocardial infarction remains a significant cause of mortality globally. High-sensitivity cardiac troponin is an essential criterion in the fourth universal definition of myocardial infarction. Our understanding of the s...Myocardial infarction remains a significant cause of mortality globally. High-sensitivity cardiac troponin is an essential criterion in the fourth universal definition of myocardial infarction. Our understanding of the structure and release mechanisms of troponin has been updated over the last decade, facilitated by ever more sensitive assays. This review initially outlines the structure and function of the troponin complex, then details the currently proposed mechanisms of release and elimination of troponin. It concludes by using this updated understanding to critique the current universal definition of myocardial infarction and injury.
Ann Clin Biochem
· 2026 May · PMID 40877033
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BackgroundDiagnosing acute heart failure in patients presenting with acute dyspnea remains challenging. Current methods, including natriuretic peptide measurement and echocardiography, are time-consuming and not always i...BackgroundDiagnosing acute heart failure in patients presenting with acute dyspnea remains challenging. Current methods, including natriuretic peptide measurement and echocardiography, are time-consuming and not always immediately accessible. A novel biomarker, FILDARIA, may complement natriuretic peptides and enable faster diagnosis.MethodsIn this study (ClinicalTrials.gov: NCT01024049), samples were collected from 235 patients diagnosed via echocardiography: 89 with non-cardiac dyspnea (NCD), 55 with chronic heart failure (CHF), and 91 with acute heart failure (AHF). Levels of BNP and FILDARIA in each patient were measured using both ELISA and lateral flow assay tests.ResultsBNP levels were significantly elevated in AHF and CHF patients compared to NCD patients (905 vs 58 pg/mL, < .0001; and 447 vs 58 pg/mL, < .0001, respectively). Similarly, FILDARIA levels were markedly higher in AHF and CHF patients than in NCD patients (1493 vs 223 ng/mL, < .0001; and 800 vs 223 ng/mL, < .0001, respectively). The FILDARIA heart failure diagnostic rapid test device accurately identified all 91 AHF patients and correctly excluded 88 of 89 NCD patients, yielding one false positive. Overall diagnostic accuracy was 99.4% (95% CI: 96.9%-99.9%).ConclusionFILDARIA biomarker demonstrates strong potential as a rapid tool for AHF in patients with acute dyspnea. Its high accuracy and compatibility with whole blood could make it an excellent solution for point-of-care testing. Further multicentre research could facilitate wider clinical use and clarify its utility in areas such as (ClinicalTrials.gov: NCT01024049).
Richardson A, Chapman K, Graham P
… +1 more, Badrick T
Ann Clin Biochem
· 2026 Mar · PMID 40810530
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Sepsis accounts for approximately 20% of global deaths, and early diagnosis is a critical factor in intervention. In 2017, the FDA approved procalcitonin (PCT) to guide antibiotic use for patients with suspected sepsis,...Sepsis accounts for approximately 20% of global deaths, and early diagnosis is a critical factor in intervention. In 2017, the FDA approved procalcitonin (PCT) to guide antibiotic use for patients with suspected sepsis, and there are recognized intervals for clinical interpretation. Therapeutic algorithms incorporating PCT measurement have implications for antibiotic stewardship in the age of antibiotic resistance. A 2021 review of external quality assurance programs for PCT, including the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) PCT program, highlighted variable performance between assays. We reviewed the RCPAQAP's PCT program results from 2019 to 2021 to analyse any variation in reported results. The RCPAQAP's PCT program is conducted annually and consists of a lyophilized human/bovine serum albumin base with added recombinant PCT sent to participating laboratories. Results received for the 2019, 2020 and 2021 PCT programs were analysed using two-way ANOVA with Tukey's multiple comparison test and a Student's -test to investigate variation in assay performance. We found significant variation between the different assay manufacturers at all PCT concentrations analysed. Additionally, bimodal reporting was observed, where bioMerieux/Beckman Coulter/Siemens methods had significantly higher results when compared to Roche/Abbott methods. There was also a significant increase in the average coefficient of variation between 2019 and 2020/2021, coinciding with reported method changes. Finally, variable performance of the semi-quantitative PCT method at both low and high PCT concentrations was detected. These findings suggest that clinical decision cut-offs must be validated for each assay. However, the commutability of the program material has yet to be determined.
Ann Clin Biochem
· 2026 Mar · PMID 40810499
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Background haemolysis is a recurrent problem in emergency department samples. Potassium is one of the most critical tests and sensitive to increasing levels of haemolysis. Haemolysis results in a large number of invalid...Background haemolysis is a recurrent problem in emergency department samples. Potassium is one of the most critical tests and sensitive to increasing levels of haemolysis. Haemolysis results in a large number of invalidated potassium test results.MethodsWe set up an alert system to detect the risk of dyskalaemia based on potassium value and haemolysis index (HI). We retrospectively evaluated the effectiveness of the alert system for haemolysed blood samples from the emergency department.Results54 605 samples were included. Women more frequently had a sample with a high HI value, resulting in the invalidation of a potassium test result (3.22% vs 2.35%, < 0.001). In the case of haemolysed samples, the frequency of alerts for hyperkalemia risk was similar in women and men. Hypokalaemia was significantly more frequent in women than in men (12.71% vs 9.38%, < 0.001). Among the haemolyzed samples, no hypokalaemia risk alerts were observed and 42 patients had a hyperkalaemia risk alert. For these patients, the potassium value of a second sample was significantly higher in patients with an alert on the first sample (4.85 mmol/L vs 4.0 mmol/L, < 0.001), with a higher rate of hyperkalaemia (57.14% vs 4.76%, < 0.001) and critical hyperkalaemia (17.86% vs 0.3%, < 0.001). Negative predictive value and positive predictive value to detect hyperkalaemia were 90.4% [89.6-91] and 41.3% [25.5%-59.1%].ConclusionsOur alert system was effective to detect the risk of hyperkalemia, and could help clinicians to better target patients requiring repeat sampling for potassium.
Bramley R, Herrera D, Barski R
… +1 more, Henderson M
Ann Clin Biochem
· 2026 Mar · PMID 40810356
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Fourier-transformed infrared (FTIR) spectroscopy is a frequently requested test in patients with kidney stones. It is considered particularly useful when routine stone urine screens do not identify any significant abnorm...Fourier-transformed infrared (FTIR) spectroscopy is a frequently requested test in patients with kidney stones. It is considered particularly useful when routine stone urine screens do not identify any significant abnormalities. This case report describes a patient with undiagnosed adenine phosphoribosyltransferase (APRT) deficiency, a disorder presenting with kidney stones, who had initial symptoms at 16 months of age but no diagnosis until they were 6 years old. Initial investigations including a urine stone screen did not show significant abnormalities; however, FTIR analysis suggested the stones had a significant component identified as lansoprazole, a drug the patient was not taking. After repeated stone formation, urinary tract infections and inpatient stays, the disorder was identified incidentally during validation of a method for purine and pyrimidines in urine. This case highlights that FTIR analysis, although useful, has pitfalls and that other investigations are of equal value in reaching a diagnosis.
Karnani-Khemlani SS, de la Vega-Prieto MJ, Padrón-Morales JR
… +5 more, Gómez-Bernal F, Laburu-Dañobeitia E, Rodríguez-García M, Cabana-Ramos D, Luis-Lima S
Ann Clin Biochem
· 2026 Mar · PMID 40794022
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This article describes the case of a 66-year-old man who attended the emergency department due to a decrease in the level of consciousness. When determining creatinine in blood plasma using the enzymatic method on the Ro...This article describes the case of a 66-year-old man who attended the emergency department due to a decrease in the level of consciousness. When determining creatinine in blood plasma using the enzymatic method on the Roche cobas c702® (Roche Diagnostics, Manheim, Germany), an undetectable creatinine value was obtained. Recently, both the literature and the manufacturer of the assay have described that the toxic metabolite of paracetamol, N-acetyl-p-benzoquinone imine, interferes with the enzymatic measurement of creatinine. Therefore, the concentration of paracetamol was determined in the same sample confirming toxic levels. On the other hand, the determination of creatinine by the Jaffe method did not present such interference. This case underlines the importance of determining creatinine by non-enzymatic methods in cases of paracetamol overdose in order to correctly assess renal function.
Chong DH, Mattman A, Dou A
… +9 more, So A, Lim HJ, Shi J, Cleve R, Schaeffer DF, Lam EC, Telford JJ, Chen LY, Carruthers MN
Ann Clin Biochem
· 2026 Mar · PMID 40776576
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BackgroundIgG4-related disease (IgG4-RD) is an inflammatory disease that can clinically mimic pancreatic and hepatobiliary cancer. Serum carbohydrate antigen 19-9 (CA19-9) is a tumour marker that is frequently used to ai...BackgroundIgG4-related disease (IgG4-RD) is an inflammatory disease that can clinically mimic pancreatic and hepatobiliary cancer. Serum carbohydrate antigen 19-9 (CA19-9) is a tumour marker that is frequently used to aid in the diagnosis of biliary cancer. There have been reported cases that patients with IgG4-RD also have elevated CA19-9.MethodsThis study has two components, first, a quality assurance component that observes paired IgG4 and CA19-9 measurements from patients with unknown diagnoses were compared to determine if serum IgG4 interferes with CA19-9 measurement. In addition, a mixing study is used to investigate if high levels of IgG4 interfered with CA19-9 measurements. Second, a retrospective chart review was performed to compare patients diagnosed with IgG4-RD with normal versus elevated CA19-9.ResultsAmong 487 unique individuals with paired measurements, no association between CA19-9 and serum IgG4 was found. Mixing studies revealed no interference. Among 20 patients with IgG4-RD, 11 had elevated CA19-9 (median 150 kU/L) and nine had normal CA19-9. There was no difference in bilirubin between the two groups (63.2 µmol/L vs 39.4 µmol/L, = .47).ConclusionThere is no relationship between CA19-9 and serum IgG4. Patients with IgG4-RD and elevated CA19-9 did not have higher bilirubin than those with normal CA19-9. Together, these results suggest that elevated CA19-9 in IgG4-RD may be related to the disease rather than to interference from high serum IgG4 or from biliary obstruction.
Kawaguchi N, Koyano K, Morita H
… +15 more, Pengiran Mohamad Fadly DNRAC, Shinabe Y, Noguchi Y, Arioka M, Nakao Y, Ozaki M, Nakamura S, Kondo S, Konishi Y, Kuboi T, Okada H, Yasuda S, Itoh S, Murao K, Kusaka T
Ann Clin Biochem
· 2026 Mar · PMID 40728869
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BackgroundBilirubin photoisomers, generated during phototherapy or incidental light exposure, may interfere with direct bilirubin (DB) measurement using the bilirubin oxidase method. This interference is particularly rel...BackgroundBilirubin photoisomers, generated during phototherapy or incidental light exposure, may interfere with direct bilirubin (DB) measurement using the bilirubin oxidase method. This interference is particularly relevant in neonates, who physiologically exhibit elevated levels of unconjugated bilirubin.MethodsResidual serum samples from 30 neonates were irradiated under controlled conditions to selectively produce bilirubin configurational isomers (BCIs) and structural isomers (BSIs). DB and total bilirubin (TB) were measured pre- and post- irradiation using the bilirubin oxidase method. BCI and BSI concentrations were quantified using high-performance liquid chromatography (HPLC), and their contributions to DB values were evaluated using linear and multiple regression analyses.ResultsPost-irradiation, DB levels increased significantly in correlation with BCI and BSI concentrations. Approximately 11% of BCI and 32% of BSI were quantified as DB using the bilirubin oxidase method. These findings were consistent across both individual and multiple regression models.ConclusionsBilirubin photoisomers significantly influence DB values measured by the bilirubin oxidase method, potentially leading to overestimation of conjugated bilirubin. In neonatal care, accurate interpretation of DB values requires attention to sample handling and awareness of photoisomer interference, particularly under light-expose conditions.
Ann Clin Biochem
· 2026 Mar · PMID 40728863
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Over the past 50 years, External Quality Assessment (EQA) Schemes in the UK have changed from being overseen by the Department of Health and Social Security (DHSS) to a self-funding model post-1990, increasing competitio...Over the past 50 years, External Quality Assessment (EQA) Schemes in the UK have changed from being overseen by the Department of Health and Social Security (DHSS) to a self-funding model post-1990, increasing competition among schemes. Despite reforms, there is no single source for assessing UK laboratories' performance. Laboratories often use a single manufacturer, which can restrict laboratories to having to use a poor method for some assays. Regulatory changes like the EU In Vitro Diagnostics Regulation (IVDR) impact manufacturers. The Medicines & Healthcare products Regulatory Agency (MHRA) oversees assay performance, focusing on patient harm. Participation in EQA is mandatory for ISO 15189 accreditation, but the holistic quality of EQA services vary. Four cases studies (calcium, testosterone, paracetamol and total bilirubin) are presented that illustrate how the current systems are being used in practice. These show different elements of quality assurance, but crucially in all cases patient management will have been impacted. Most performance issues are manufacturer-related. EQA helps monitor assay quality, but gaps in oversight remain. Diagnostic reform is progressing, but differences in assay results pose risks. Laboratories must collaborate with stakeholders to ensure high-quality services. Mechanisms are needed to rectify sub-optimal assays. The current system can lead to patient misdiagnosis or incorrect clinical pathways. A mechanism is required to ensure accurate results for the public, within acceptable error margins, and at a sustainable cost for the NHS.
Flannery C, Griffin A, Quinn J
… +2 more, Loughrey C, Srinivasan S
Ann Clin Biochem
· 2026 Mar · PMID 40728856
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BackgroundCalculated globulin, based on direct measurement of total protein and albumin, can be a useful addition to the routinely requested liver profile. However, a reference interval, established using CLSI EP28-A3c r...BackgroundCalculated globulin, based on direct measurement of total protein and albumin, can be a useful addition to the routinely requested liver profile. However, a reference interval, established using CLSI EP28-A3c recommended direct methods, is lacking for the commonly used Roche method [albumin bromocresol green (BCG), total protein (biuret)].MethodsThis direct reference interval study was carried out between January and March 2024, based on Roche methods for total protein (biuret) and albumin (BCG). Reference individuals comprised 310 highly selected adults from primary care, ages ranging from 16 to 89 years. The CLSI guideline, EP28-A3c, was strictly followed. We also established a reference interval using an indirect approach for comparative purposes, using results from 8466 unselected primary care patients.ResultsThe reference interval for calculated globulin established using direct sampling techniques was 23 g/L (90% CI 22-24 g/L) - 35 g/L (90% CI 34-36 g/L). The reference interval established using indirect sampling techniques in a much larger unselected reference group was 22 g/L (90% CI 22-22 g/L) - 37 g/L (90% CI 37-37 g/L).ConclusionsWe have established a reference interval for calculated globulin, specific to the Roche total protein and BCG albumin methods. This will be a useful tool for other laboratories which use the Roche BCG albumin method, allowing adoption of this reference interval with a simple transference study. The range was a little broader but not materially altered (medians exactly the same) when strict exclusion criteria were removed and also when using a data mining approach, which resulted in a 27-fold larger reference group.