Batur T, Balahoroğlu R, Karaoglan H
… +1 more, Sezer S
Ann Clin Biochem
· 2026 May · PMID 42103445
·
Publisher ↗
IntroductionWhile conclusions regarding the effects of serum separator tubes on some laboratory tests have been reached in previous studies, the effects of these tubes on the B12 test have not been adequately investigate...IntroductionWhile conclusions regarding the effects of serum separator tubes on some laboratory tests have been reached in previous studies, the effects of these tubes on the B12 test have not been adequately investigated. This study aimed to determine the effects of the serum separator tube position after centrifugation on serum B12 test results.Materials and MethodsTwo blood samples were collected by venipuncture into 5-mL Pirmax serum separator tubes from each of the 30 volunteers. The effects of the tube position after centrifugation, gentle mixing 5-10 times, recentrifugation, and short-term (15 min) standing of the tubes in an upright position on serum B12 test results were examined in a step-by-step manner. The B12 analyses were performed in an ADVIA Centaur XPT autoanalyzer using a chemiluminescence method. Comparisons between the groups were evaluated for statistical and clinical significance.ResultsB12 levels were higher in the samples positioned horizontally than in the samples positioned vertically ( < 0.001). The total effect of horizontal position and mixing was abolished by recentrifugation ( = 0.091). The horizontal tube position and sample mixing led to an exceedance of the total allowable error limit.ConclusionsThe use of serum separator tubes may be associated with spuriously elevated serum B12 concentrations in the ADVIA Centaur XPT assay. The serum separator tubes should be kept upright in the post-centrifugation period prior to B12 analysis. We recommend recentrifugation if the tubes have been held in a horizontal position and/or the samples have been mixed.
Ann Clin Biochem
· 2026 May · PMID 42103441
·
Publisher ↗
BackgroundVitamin B12 deficiency can cause anaemia, fatigue, and neurological sequelae. Total B12 assays may not be reflective of tissue B12. Methylmalonic acid (MMA) can assess tissue B12 more accurately. NICE published...BackgroundVitamin B12 deficiency can cause anaemia, fatigue, and neurological sequelae. Total B12 assays may not be reflective of tissue B12. Methylmalonic acid (MMA) can assess tissue B12 more accurately. NICE published clinical guidelines on Vitamin B12 deficiency in adults in 2024. They outlined MMA testing in two scenarios: in patients where nitrous oxide use is possible or who have an indeterminate total B12 result (180-350 ng/L) alongside symptoms or signs of B12 deficiency. MMA testing is costly, not readily available, and time consuming, so increased use will have implications.MethodsThis is a Case note review of patients who had MMA requested one year prior to and one year post-NICE NG239 publication. Audit standards followed were NG239 indications for MMA testing.ResultsIn the year after NG239, MMA testing increased by 96% (57 to 112). Whilst only 47% would have meet NG239 testing criteria in the prior group, this increased to 79% in the post group. More were diagnosed with B12 deficiency (16% prior and 21% post), and more commenced on B12 treatment (14% prior and 19% after). Comparing simultaneous total B12 and MMA results suggests an increase in the upper reference interval of the indeterminate range to 375 ng/L could be considered.ConclusionsDemand for MMA testing almost doubled after NG239 was published, though requests appeared much more appropriate. Whilst laboratory costs increased, there may have been savings elsewhere in the system. Further analysis would be required to review the extent of these healthcare savings in practice.
Ann Clin Biochem
· 2026 Mar · PMID 41876205
·
Publisher ↗
BackgroundBiotin is commonly used in many commercial assays. It is known that exogenous biotin can interfere with these tests, however, not all manufacturers have issued warnings or reassurances. Interference can lead to...BackgroundBiotin is commonly used in many commercial assays. It is known that exogenous biotin can interfere with these tests, however, not all manufacturers have issued warnings or reassurances. Interference can lead to increased or decreased concentrations of an analyte depending on the assay format. We assessed the effect of biotin interference on all relevant assays performed in our laboratory. We investigated a variety of concentrations ranging from the recommended daily intake up to very high dose supplementation to determine the level at which a particular assay may be affected.MethodsSamples were spiked to give estimated serum concentrations equivalent to doses of 0.05-3600 mg/day exogenous biotin. Each spiked sample was tested and the result compared to a baseline. Biotin interference was deemed to have taken place if the spiked value exceeded the allowable uncertainty of measurement.ResultsNot all assays utilising biotin were affected. We confirmed interference claims made by Manufacturers. However, a few of these assays showed that biotin levels below those stated in safety notices could cause some degree of interference. Three assays for which there had not been a warning were shown to be affected.ConclusionsIn house checks should be performed on all assays containing biotin as a reagent. This allows the laboratory to understand performance characteristics and dosage effects for causing potential interference. Our data provides a guide for the level of biotin which may cause false positive or false negative results.
Dissanayake GN, Fourie H, Fricker G
… +4 more, Thayabaran D, Patel M, Granne I, Shine B
Ann Clin Biochem
· 2026 Mar · PMID 41863476
·
Publisher ↗
Case oneA young woman presented to the Early Pregnancy Assessment Unit (EPAU) with abdominal pain, amenorrhoea and variably positive home-pregnancy tests. On review, a point-of-care test (POCT) for urine beta-HCG (β-HCG)...Case oneA young woman presented to the Early Pregnancy Assessment Unit (EPAU) with abdominal pain, amenorrhoea and variably positive home-pregnancy tests. On review, a point-of-care test (POCT) for urine beta-HCG (β-HCG) was negative but a blood test using the Abbott i-STAT β-HCG POCT device was positive. Initial transvaginal ultrasound did not demonstrate an intra- or extra-uterine pregnancy. Over the following 2 months, weekly plasma POCT iSTAT β-HCG checks remained positive. After a further ultrasound suggesting a possible ectopic pregnancy, the patient underwent a diagnostic laparoscopy which was unremarkable. Post-operatively, POCT iSTAT β-HCG levels remained elevated, and a blood sample was sent for laboratory analysis revealing an undetectable β-HCG of <1.20 IU/L (reference interval 0-4).Case twoA middle-aged woman presented to the emergency department with mons pubis pain and swelling and was admitted to the gynaecology ward for drainage of bilateral abscesses. On review, she had raised blood β-HCG levels, measured using the Abbott i-STAT POCT device. A subsequent blood sample sent for laboratory analysis showed β-HCG levels within the post-menopausal reference interval. In both cases, POCT immunoassay interference was confirmed by consistent results produced when contemporaneous samples were analysed by different analytical platforms. Immunoassay interference, though rare, can lead to inaccurate results from POCT devices, potentially impacting patient diagnosis and management. Clinical teams should remain vigilant for this possibility; if test results do not align with clinical expectations, it is essential to promptly send a blood sample for laboratory analysis.
Ishida H, Ozawa N, Tachikawa M
… +5 more, Nagasawa H, Shirakami Y, Watanabe T, Okura H, Kikuchi R
Ann Clin Biochem
· 2026 Mar · PMID 41844342
·
Publisher ↗
BackgroundHeart failure (HF) is a growing global burden. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) guides diagnosis, assay cost and analyzer availability limit routine use. Routine laboratory data ma...BackgroundHeart failure (HF) is a growing global burden. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) guides diagnosis, assay cost and analyzer availability limit routine use. Routine laboratory data may offer a low-cost triage alternative.MethodsWe developed and validated an interpretable decision tree to stratify the risk of elevated NT-proBNP >300 pg/mL and assessed deployment in a diagnostic support system (DSS). We analyzed 19,889 encounters at Gifu University Hospital (Aug 2022-May 2024). All 20 candidate predictors were included without prior feature selection to capture non-linear associations. Hyperparameters were tuned by 10-fold cross-validation. Final classification used a fixed decision rule optimized for high sensitivity (≥0.90 in training) to support effective triage. Performance comprised AUROC (DeLong 95% CIs) and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy (Wilson 95% CIs) on an internal hold-out set (n = 3978) and a temporal external cohort (n = 14,903; Jun 2024-Jun 2025). Analyses were complete-case with no imputation.ResultsThe decision tree inherently utilized clinically relevant predictors including serum albumin, eGFR, and age. Internal test performance: AUROC 0.804 (0.791-0.818); sensitivity 0.879 (0.863-0.893); specificity 0.505 (0.484-0.526); and accuracy 0.674 (0.660-0.689). External performance within the DSS: AUROC 0.806 (0.799-0.813); sensitivity 0.882 (0.874-0.890); specificity 0.518 (0.508-0.529); and NPV 0.852 (0.842-0.861). Calibration and decision-curve analysis supported clinical utility.ConclusionsAn interpretable tree built from routine laboratories detects clinically relevant NT-proBNP elevation with high sensitivity and performs robustly after deployment. This scalable, low-cost approach could enable risk-directed triage and more efficient resource allocation.
S AN, D A RD, Pangaluri R
… +2 more, V M V, K A AS
Ann Clin Biochem
· 2026 Mar · PMID 41838882
·
Publisher ↗
The presence of paraproteins in multiple myeloma can cause analytical interference, resulting in unusual and misleading biochemical outcomes. An uncommon but clinically relevant finding is the reporting of a negative dir...The presence of paraproteins in multiple myeloma can cause analytical interference, resulting in unusual and misleading biochemical outcomes. An uncommon but clinically relevant finding is the reporting of a negative direct bilirubin result on wet chemistry analyzers-an impossible outcome that strongly suggests analytical interference. A 60-year-old male presented with nonspecific symptoms. Liver function tests carried out on a wet chemistry analyzer indicated a total bilirubin of 0.39 mg/dL and a direct bilirubin of -7.67 mg/dL, which was not physiologically possible. There was no evidence of jaundice, and imaging appeared normal. Repeat testing with a dry chemistry analyzer indicated a total bilirubin of 1.0 mg/dL and a direct bilirubin of 0.1 mg/dL, aligning with the clinical picture. Further investigations confirmed the diagnosis of multiple myeloma with IgG-kappa monoclonal gammopathy. The discrepancy was attributed to paraprotein interference in the wet chemistry method. This case highlights a rare but important laboratory artifact-negative direct bilirubin due to paraprotein interference-and emphasizes the reliability of dry chemistry in such scenarios. Awareness of this interference is important for accurate diagnosis and avoiding unnecessary workup.
Morishige A, Nishioka M, Nakabayashi Y
… +8 more, Ishiguro A, Shinkawa K, Fujinaga A, Kobayashi T, Fukuda M, Suehiro Y, Ohta Y, Yamasaki T
Ann Clin Biochem
· 2026 Mar · PMID 41837569
·
Publisher ↗
Background Urinary C-peptide testing is widely used to evaluate insulin secretion capacity from pancreatic β-cells. We report a case in which urinary C-peptide showed abnormally high levels during treatment with an angio...Background Urinary C-peptide testing is widely used to evaluate insulin secretion capacity from pancreatic β-cells. We report a case in which urinary C-peptide showed abnormally high levels during treatment with an angiotensin receptor-neprilysin inhibitor (ARNI). Case presentation The patient was a 54-year-old man undergoing treatment for type 2 diabetes mellitus and hypertension. Following an abnormal electrocardiogram during a health check-up, he was diagnosed with aortic valve insufficiency. During admission to the diabetes and endocrinology department for preoperative glycemic control, a clinical laboratory technologist first recognized a marked discrepancy between urinary and serum C-peptide results and reported this to the attending physician, prompting further investigation. A literature review revealed reports suggesting that ARNI administration may suppress C-peptide metabolism, potentially leading to elevation of measured values. Results The patient's excreted urinary C-peptide level decreased markedly after ARNI therapy was discontinued, suggesting that ARNI influences an increase in urinary C-peptide. Conclusions When excreted urinary C-peptide is abnormally elevated and discrepant from the serum C-peptide level, it is important to confirm ARNI use and follow laboratory-driven recommendations for retesting after discontinuation if needed. Prompt reporting of this finding by the clinical laboratory is essential for the accurate assessment of insulin secretion capacity.
Ann Clin Biochem
· 2026 Mar · PMID 41773499
·
Publisher ↗
BackgroundExposure of plasma to low temperatures induces the conversion of prorenin to renin, causing falsely elevated levels of renin. This also happens at storage temperatures of -20°C. Our survey evaluated the pre-ana...BackgroundExposure of plasma to low temperatures induces the conversion of prorenin to renin, causing falsely elevated levels of renin. This also happens at storage temperatures of -20°C. Our survey evaluated the pre-analytical procedures used by clinical laboratories in the Netherlands for renin testing and assessed their awareness of recent studies on cryoactivation and their impact on pre-analytical procedures.MethodsA nine-question online survey about pre-analytical conditions for renin measurements in clinical laboratories was distributed by the Foundation for Quality Assessment in Medical Laboratory Diagnostics (SKML) to 106 clinical laboratories in the Netherlands participating in the external quality assessment scheme for hormone measurements.ResultsOf the 42 labs that responded, pre-analytical practices varied considerably. Time limits for sample receipt ranged from none (31%, n = 13) to <4 h (57%, n = 24) or >4 h (5%, n = 2). Most laboratories transported and centrifuged samples at room temperature (90% and 93%; n = 38 and 39). Storage conditions differed: 79% (n = 33) stored at -20°C, 17% (n = 7) at -80°C, 2% (n = 1) at -40°C, and 2% (n = 1) at room temperature. Twenty-two respondents (52%) were aware of recent literature, and 8 (36%) had changed or planned to change procedures accordingly. Overall, only eight laboratories (19%) followed all recommended steps to minimize cryoactivation.ConclusionsThis survey shows considerable inconsistency in pre-analytical procedures of renin testing in clinical laboratories in the Netherlands. Despite moderate awareness of recent evidence, implementation of optimal preanalytical procedures remains limited. The survey results show that guidelines and scientific evidence have not been fully implemented, and that awareness of the latest evidence does not directly lead to a change in practice.
Shafiq S, Roberts L, Williams G
… +1 more, Shorten R
Ann Clin Biochem
· 2026 Mar · PMID 41769725
·
Publisher ↗
BackgroundThe NHS accounts for approximately 4-5% of England's total carbon footprint and was the first healthcare organisation to commit to a net-zero target. Reducing the inappropriate use of diagnostic tests could pla...BackgroundThe NHS accounts for approximately 4-5% of England's total carbon footprint and was the first healthcare organisation to commit to a net-zero target. Reducing the inappropriate use of diagnostic tests could play a meaningful role in reaching this goal. In 2024, the microbiology laboratory at Lancashire Teaching Hospitals NHS Foundation Trust received >90,000 urine and >15,000 wound samples. Local audit data highlights samples are sent for testing in the absence of clinical signs and symptoms of infection. Furthermore, 25 % of superficial swabs and 10% of urines grew mixed-faecal organisms.PurposeThe aim was to implement a diagnostic stewardship intervention to reduce inappropriate urine and wound swab submissions from primary care and estimate associated carbon savings.Research DesignA pre-analytical stage diagnostic stewardship intervention was implemented consisting of a computerised clinical decision support tool (CCDS). The tool prompts clinicians, using evidence-based guidance, on when to obtain samples for testing. Study Sample: 3-month intervention period data was compared with two 3-month pre-intervention periods (I and II).Data AnalysisThe UK Government 2024 greenhouse gas conversion factors were used to calculate the total COe associated with testing urine and wound samples. ResultsComparing number of samples received during the intervention period with pre-intervention II, urine samples decreased by 10.2%, saving 190.5 kg COe. Similarly, wound samples decreased by 12.9%, saving 80 kg COe.ConclusionThe CCDS tool effectively reduced unnecessary testing and associated carbon emissions, supporting the NHS's net-zero ambitions. Similar tools can be employed in other areas of pathology to reduce the impact of inappropriate testing whilst supporting sustainable healthcare.
Kume Y, Ohkubo M, NaKatuka N
… +5 more, Aritake-Okada S, Yoshikawa N, Yoshida T, Isago H, Kurano M
Ann Clin Biochem
· 2026 Mar · PMID 41769712
·
Publisher ↗
BackgroundBlood glucose concentrations decrease after blood collection. We recently developed novel blood collection tubes containing inosine added to sodium fluoride (NaF; FI tubes), which effectively inhibits post-coll...BackgroundBlood glucose concentrations decrease after blood collection. We recently developed novel blood collection tubes containing inosine added to sodium fluoride (NaF; FI tubes), which effectively inhibits post-collection blood glucose decline. However, the underlying mechanism remains unclear. In this study, we examined the mechanism by which inosine inhibits blood glucose consumption by erythrocytes and assessed glucose transporter (GLUT) activity.MethodsATP levels were measured in erythrocytes treated with inosine, and metabolomic changes were analyzed using GC-MS. In addition, glucose uptake tests were performed.ResultsIn patients' blood samples, FI tubes suppressed the post-collection decline in blood glucose levels more effectively than conventional NaF tubes, regardless of baseline blood glucose levels. FI tubes attenuated the time-dependent decrease in ATP levels; however, similar to that in conventional NaF tubes, ATP levels in erythrocytes in FI tubes were nearly zero after 4 h. Metabolic analysis demonstrated a decrease in the levels of glucose and glycolytic metabolites, such as 2-phosphoglycerate and phosphoenolpyruvate, in inosine-treated erythrocytes. Glucose uptake assays revealed that inosine significantly inhibited glucose uptake, indicating suppression of GLUT activity.ConclusionsInosine inhibits glucose uptake in erythrocytes primarily via the suppression of GLUT activity. It also inhibits erythrocyte hemolysis by temporarily maintaining intracellular ATP levels.
Ann Clin Biochem
· 2026 Feb · PMID 41697010
·
Publisher ↗
BackgroundPneumatic tube systems (PTSs) have revolutionized sample transport efficiency, yet concerns about sample integrity remain unresolved. This study evaluated the AirLab system (PazKorea, Hanam-si, Korea), a novel...BackgroundPneumatic tube systems (PTSs) have revolutionized sample transport efficiency, yet concerns about sample integrity remain unresolved. This study evaluated the AirLab system (PazKorea, Hanam-si, Korea), a novel high-speed carrier-free PTS, for its impact on sample integrity and turnaround time (TAT) under controlled pre-analytical conditions.MethodsBlood specimens were collected in duplicate from 42 participants (30 healthy volunteers and 12 outpatients with chronic alcohol use) and randomly assigned to PTS or manual transport. Multiple laboratory parameters were analysed, including chemistry, hematology, coagulation, and heavy metal tests. Sample integrity was assessed by comparing test results between transport methods using both statistical analysis and clinical significance criteria based on total allowable error (TAE). Pre-analytical, analytical and total TATs were compared between transport methods.ResultsAmong 20 measurands, four showed statistically significant differences: glucose, potassium (K), lactate dehydrogenase (LD), and mean corpuscular volume (MCV). PTS yielded higher results for glucose, K and LD (average percentage biases: 1.88%, 2.01%, and 15.80%, respectively), while producing lower results for MCV (average percentage bias: -0.47%). Only LD showed clinically significant differences, as its average percentage bias exceeded its desirable TAE. PTS significantly reduced both pre-analytical and total TATs for all test types, with reductions ranging from 12.12% to 22.82% and 7.32% to 8.98%, respectively, whereas analytical TATs remained unchanged.ConclusionsThe AirLab system effectively preserves sample integrity for most laboratory parameters while improving operational efficiency through TAT reduction. However, the clinically significant elevation in LD levels necessitates careful interpretation when employing this system in clinical laboratories.
Ann Clin Biochem
· 2026 Feb · PMID 41697008
·
Publisher ↗
BackgroundFaecal immunochemical tests (FIT) detect and quantify faecal haemoglobin (f-Hb) to triage symptomatic primary care patients for the risk of colorectal cancer (CRC).MethodFIT was performed using FOB Gold® on a S...BackgroundFaecal immunochemical tests (FIT) detect and quantify faecal haemoglobin (f-Hb) to triage symptomatic primary care patients for the risk of colorectal cancer (CRC).MethodFIT was performed using FOB Gold® on a Siemens ADVIA Chemistry XPT analyser at Stepping Hill Hospital. Diagnostic accuracy was assessed by following up FIT results between June 2023 and June 2024. Results of ≥10 g of haemoglobin per gram of faeces (µg/g) were considered as positive. The FIT results were matched with data from the Somerset cancer register, concluding if patient had CRC or non-CRC findings.ResultsA total of 12,640 patients were included in this study. Colonoscopies (or contrast CT) were performed on 1476 patients with f-Hb results of ≥10 µg/g and on 617 patients with f-Hb <10 µg/g as the clinician had further concerns. A total of 98 cancers were found (89 had f-Hb ≥10 µg/g and 9 had f-Hb <10 µg/g). The remaining 10,547 with f-Hb <10 µg/g were considered as non-CRC due to lack of follow-up for >6 months. Using the 10 µg/g cut-off, FOB Gold® sensitivity for CRC was 90.8% and the specificity was 88.9%; the positive predictive value was 6.0% and the negative predictive value was 99.9%. The receiver operating characteristic curve had an area under the curve of 0.92 (95% CI 0.89 to 0.95).ConclusionFOB Gold® has comparable diagnostic performance for detecting CRC in symptomatic primary care patients as other FIT systems at 10 µg/g.
Ann Clin Biochem
· 2026 Feb · PMID 41687598
·
Publisher ↗
Glycerol kinase deficiency (GKD) is a rare X-linked metabolic disorder often presenting in infancy or childhood. In adults, it may remain undiagnosed due to nonspecific symptoms or incidental biochemical findings. We rep...Glycerol kinase deficiency (GKD) is a rare X-linked metabolic disorder often presenting in infancy or childhood. In adults, it may remain undiagnosed due to nonspecific symptoms or incidental biochemical findings. We report a case of incidental GKD diagnosis in an adult male presenting with hyponatraemia and acute kidney injury (AKI). Discrepancies between triglyceride concentrations and lipaemic indices prompted further investigation, revealing severe hyperglycerolaemia due to GKD. This case highlights the importance of considering GKD in adults with unexplained hypertriglyceridaemia, especially when triglyceride concentrations are discordant with lipaemic indices and other lipid profile parameters. Genetic testing confirmed that the patient was hemizygous for a likely pathogenic variant in the GK gene, consistent with a genetic diagnosis of glycerol kinase deficiency.
Rodney M, Rankin K, Butler J
… +3 more, Thompson S, Florkowski CM, King RI
Ann Clin Biochem
· 2026 Feb · PMID 41665094
·
Publisher ↗
Strict homoeostatic control of potassium is necessary for normal muscle and neural function, and as a result, hyperkalaemia can be life-threatening and requires timely management. Prior to treating the patient, however,...Strict homoeostatic control of potassium is necessary for normal muscle and neural function, and as a result, hyperkalaemia can be life-threatening and requires timely management. Prior to treating the patient, however, it is important to determine if hyperkalaemic blood test results are authentic and not due to pre-analytical factors as treatment in this context may provoke potentially dangerous hypokalaemia. We present the case of a 47-year-old female referred for further investigation following 2 years of otherwise unexplained intermittent hyperkalaemia. Her highest recorded potassium was 8.9 mmol/L (reference interval: 3.5-5.2 mmol/L). She was otherwise healthy, not on regular medications, and asymptomatic during these episodes. There was no evidence of associated electrocardiogram (ECG) changes. She had been referred to the Emergency Department twice in 6 months due to hyperkalaemia, but these episodes resolved on repeat testing without any intervention. Further investigation revealed a significant time- and temperature-dependent increase in potassium concentration in whole blood samples, compared to a control. single gene testing revealed a heterozygous variant, c.1123 C>T, p. (Arg375Trp), consistent with a diagnosis of familial pseudohyperkalaemia (FP). This is an autosomal dominant condition, which results in increased efflux of potassium from red blood cells at sub-physiological temperatures. Whilst this is an phenomenon, unless recognised it poses a clinical risk to patients as they may be treated erroneously.