Clinical biochemistry最新文献

{"title":"The hemopexin-apolipoprotein B product: a novel biomarker integrating oxidative stress and lipid metabolism for coronary artery disease risk stratification","authors":"Yinsheng Jin ,&nbsp;Kun Chen ,&nbsp;Qunxiong Fan","doi":"10.1016/j.clinbiochem.2025.111043","DOIUrl":"10.1016/j.clinbiochem.2025.111043","url":null,"abstract":"<div><h3>Objective</h3><div>We hypothesized that the Hemopexin-Apolipoprotein B product (Hpx·apoB), a composite biomarker integrating lipid dysregulation and oxidative stress pathways, would improve coronary artery disease (CAD) diagnosis and risk stratification.</div></div><div><h3>Methods</h3><div>This single-center cross-sectional study included 460 participants (350 CAD patients, 110 non-significant CAD controls). Plasma hemopexin (Hpx) was measured by liquid chromatography – tandem mass spectrometry, and the Hpx·apoB product was calculated. Multivariate logistic regression analyzed its CAD association, while area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI) assessed its incremental predictive value over conventional risk factors and established models (Framingham, SCORE2).</div></div><div><h3>Results</h3><div>The Hpx·apoB product was significantly elevated in CAD patients compared to controls (median [IQR]: 2.35 [1.80–3.15] vs. 1.72 [1.30–2.25] mg²/L², p &lt; 0.001). After adjusting for traditional cardiovascular risk factors, Hpx·apoB remained an independent predictor of CAD (Odds Ratio [OR] = 2.61, 95 % Confidence Interval [CI]: 1.48–4.60, p = 0.001). Adding Hpx·apoB to a baseline model with conventional risk factors (hs-CRP + LDL-C) significantly improved the AUC from 0.75 (95 % CI: 0.70–0.80) to 0.83 (95 % CI: 0.79–0.87; p for ΔAUC &lt; 0.001), with a continuous NRI of 0.352 (p &lt; 0.001) and an IDI of 0.098 (p &lt; 0.001). Furthermore, integrating Hpx·apoB into the Framingham and SCORE2 models also yielded significant improvements in risk reclassification (NRI = 29.5 % and 39.8 %, respectively; both p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>The Hpx·apoB biomarker, combining oxidative stress and lipid metabolism, independently predicts CAD presence and severity while improving existing risk models’ accuracy, enhancing clinical risk stratification.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111043"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of kidney function on the prognostic value of cardiac troponin","authors":"Rasmus Bo Hasselbalch ,&nbsp;Martin Schultz ,&nbsp;Nicholas Carlson ,&nbsp;Nina Strandkjær ,&nbsp;Sophie Sander Knudsen ,&nbsp;Alexander Holst Kronborg ,&nbsp;Kristian H. Kragholm ,&nbsp;Mikkel Porsborg Andersen ,&nbsp;Henning Bundgaard ,&nbsp;Christian Torp-Pedersen ,&nbsp;Kristin M. Aakre ,&nbsp;Kasper Karmark Iversen","doi":"10.1016/j.clinbiochem.2025.111068","DOIUrl":"10.1016/j.clinbiochem.2025.111068","url":null,"abstract":"<div><h3>Background</h3><div>Kidney function influences the concentration of cardiac troponin T (cTnT) and I (cTnI). We investigate how this impacts their prognostic ability.</div></div><div><h3>Methods</h3><div>This Danish nationwide study included patients from 2013 to 2023 with at least two measurements of Roche hs-cTnT, Abbott hs-cTnI, or Siemens hs-cTnI Vista or Atellica during the index admission. Patients were stratified by estimated glomerular filtration rate (eGFR). We assessed prognostic ability by Cox models and area under the receiver operating characteristics curve (AUC). The primary endpoint was 30-day all-cause mortality.</div></div><div><h3>Results</h3><div>We included 277,723 patients (median age 69 years, 38.4 % female) of whom 19,565 (7.0 %) died within 30 days. Almost all patients with eGFR &lt;30 ml/min/1.73 m² had myocardial injury using hs-cTnT (99.4 %) compared to hs-cTnI (85.4 %). Hazard ratios (HRs) for overall myocardial injury were higher than for acute myocardial injury and declined with worsening eGFR, particularly for hs-cTnT: HR 15.58 (95 % CI 12.77–19.00) for eGFR ≥90 ml/min/1.73 m², while estimation was impossible at eGFR 15–30 ml/min/1.73 m² due to few normal values. The highest HR for acute myocardial injury at eGFR ≥90 ml/min/1.73 m² was for hs-cTnI Abbott, HR 3.50 (95 % CI 2.79–4.38). AUC decreased with worsening eGFR across assays, 0.68–0.76 for eGFR ≥90 ml/min/1.73 m² to 0.59–0.63 for eGFR &lt;15 ml/min/1.73 m². At eGFR ≥90 ml/min/1.73 m² the optimal cutoff was 16.5 ng/l for hs-cTnT and below the sex-specific 99th percentile for all hs-cTnI assays, increasing 5–20-fold with lower eGFR for all assays.</div></div><div><h3>Conclusion</h3><div>Kidney function affects cTn prognostic performance, with reduced predictive ability and higher optimal cutoff concentrations for lower eGFR.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111068"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simple lithium measurement in capillary dried plasma microsamples collected with the HealthID PSD device","authors":"Eduarda Milena Reichert ,&nbsp;Carolina Weber Ferrareze ,&nbsp;Mayara Bernardes ,&nbsp;Giovana Piva Peteffi ,&nbsp;Amanda Pachedo Bondan ,&nbsp;Mariele Feiffer Charão ,&nbsp;Rafael Linden","doi":"10.1016/j.clinbiochem.2025.111069","DOIUrl":"10.1016/j.clinbiochem.2025.111069","url":null,"abstract":"<div><h3>Background</h3><div>Monitoring serum lithium concentrations is essential during bipolar disorder treatment. This study aimed to develop and validate a simple approach for estimating serum lithium concentrations using dried plasma spots (DPS) obtained from the HealthID PSD device after application of capillary blood.</div></div><div><h3>Methods</h3><div>Lithium was extracted using BSA solution and quantified with a colorimetric assay on an automated clinical analyzer. A chloride-based correction factor was applied to account for variable plasma volumes in DPS extracts. Analytical validation included linearity, extraction yield, imprecision, hematocrit and volume effects, chromatographic uniformity during plasma migration, and stability at different temperatures. A clinical comparison study was performed using paired serum samples and DPS from 40 patients undergoing lithium therapy. Serum-equivalent lithium concentrations were calculated by applying a multiplication factor derived from the serum-to-DPS ratio. Agreement was assessed by Passing–Bablok regression, Bland–Altman analysis, median percentage predictive error (MPPE), median absolute percentage error (MAPE), and total error (TE).</div></div><div><h3>Results</h3><div>Linearity was demonstrated from 0.1–2.5 mmol/L. Extraction yields were 93.2–95.7 %, and chloride correction significantly improved imprecision. Hematocrit (30–50 %) and applied volume (160–240 µL) showed minimal influence on corrected concentrations. Lithium remained stable for 21 days. Serum-equivalent DPS lithium showed strong correlation with serum (<em>r</em> = 0.984), no proportional or systematic bias, MPPE 0.91 %, MAPE 6.7 %, and TE 11.9 %.</div></div><div><h3>Conclusions</h3><div>Lithium can be reliably quantified in DPS generated with the HealthID PSD device using a routine colorimetric assay. The method enables stable, minimally invasive capillary microsampling suitable for clinical monitoring of lithium therapy.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111069"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-analytical considerations in the simultaneous quantification of ketone bodies, lactate, pyruvate and TCA cycle intermediates","authors":"Kaitlyn Berchier ,&nbsp;Chiara Nyffeler ,&nbsp;Stephen Bruce ,&nbsp;Clothilde Roux ,&nbsp;Jean-Marc Nuoffer ,&nbsp;Matthias Gautschi ,&nbsp;Alexander Laemmle ,&nbsp;Déborah Mathis","doi":"10.1016/j.clinbiochem.2025.111056","DOIUrl":"10.1016/j.clinbiochem.2025.111056","url":null,"abstract":"<div><h3>Background</h3><div>Accurate quantification of small metabolites such as ketone bodies (KB: β-hydroxybutyrate (BHB), acetoacetate (AcAc)), pyruvate (Pyr), lactate (Lac) and tricarboxylic acid (TCA) cycle intermediates is essential for diagnostics, therapy monitoring and metabolic research. These metabolites serve as energy substrates and signaling molecules, with their interpretation often relying on physiologically meaningful ratios (Lac/Pyr, BHB/AcAc). However, their chemical instability and susceptibility to rapid post-collection metabolism pose significant pre-analytical challenges.</div></div><div><h3>Method</h3><div>We developed an LC-MS/MS method for the simultaneous quantification of KB, Pyr, Lac and TCA cycle intermediates, and systematically evaluated pre-analytical factors affecting their stability and accuracy. We compared lithium-heparin (LH), ethylenediaminetetraacetic acid (EDTA), sodium fluoride/EDTA (NaF/EDTA) and sodium citrate (NaCit) collection tubes and deproteinized whole blood (depWB) using perchloric acid. Stability was assessed in whole blood at RT over 24 h, as well as in LH and depWB at various temperatures (RT, 4 °C, –20 °C) over 7 days.</div></div><div><h3>Results</h3><div>Pyr, Lac, AcAc and fumarate were most labile, while BHB and citrate were stable across matrices. LH-plasma with prompt centrifugation showed minimal metabolic alterations, while NaF/EDTA effectively stabilized Lac but compromised Pyr and TCA cycle intermediates. DepWB improved Lac/Pyr ratio reliability but introduced higher variability and matrix effects. NaCit induced unexpected metabolic shifts, suggesting in-vitro TCA cycle activity.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the critical impact of anticoagulants and processing conditions on metabolite stability. LH-plasma provides the best compromise for quantifying KB, Pyr and TCA cycle intermediates when processed rapidly, while depWB remains preferable for accurate Lac/Pyr ratio determination despite its higher variability.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111056"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel and known fibrinogen gene mutations in Chinese pediatric patients with congenital dysfibrinogenemia: genetic and functional characterization","authors":"Juan Huang ,&nbsp;Duocai Wang ,&nbsp;Ying Wang ,&nbsp;Yongqiang Yang ,&nbsp;Dong Peng ,&nbsp;Meizhu Luo ,&nbsp;Xiaoying Fu","doi":"10.1016/j.clinbiochem.2025.111064","DOIUrl":"10.1016/j.clinbiochem.2025.111064","url":null,"abstract":"<div><h3>Objectives</h3><div>Congenital dysfibrinogenemia (CD) is a rare inherited disorder caused by qualitative abnormalities in fibrinogen, leading to discordance between functional and antigenic fibrinogen levels. Genetic testing plays a pivotal role in confirming diagnosis and elucidating phenotypic heterogeneity. This study aims to emphasize the diagnostic value of combining coagulation assays with genetic testing and underscore the clinical heterogeneity of CD through clinical cases of novel mutations.</div></div><div><h3>Design &amp; methods</h3><div>Five pediatric patients with incidentally identified CD were diagnosed at Shenzhen Children’s Hospital. Peripheral blood samples were analyzed for coagulation parameters, including fibrinogen activity (FIB:C) by the Clauss method, fibrinogen derived from the prothrombin time (PT-dF), as well as activated partial thromboplastin time （aPTT）, PT, thrombin time (TT), and thromboelastography (TEG). Sanger sequencing was conducted to assess mutations in <em>FGA</em>, <em>FGB</em>, and <em>FGG</em> genes.</div></div><div><h3>Results</h3><div>Two unrelated patients harbored a known heterozygous mutation in <em>FGG</em> (c.902G &gt; A; p.Arg301His). Two novel heterozygous mutations were identified: <em>FGA</em> (c.113G &gt; A; p.Arg38Lys) and <em>FGG</em> (c.902G &gt; T; p.Arg301Leu). A homozygous mutation in <em>FGB</em> (c.292G &gt; A; p.Ala98Thr) was detected in another patient; this variant has been reported only twice before in the literature. All patients were asymptomatic. Coagulation testing revealed consistently decreased FIB:C with normal PT-dF, characteristic of CD. TEG analysis showed variable alterations in fibrinogen-related parameters, although no consistent genotype–phenotype correlation was observed.</div></div><div><h3>Conclusion</h3><div>This study expands the genetic and phenotypic spectrum of CD in children, reporting two novel mutations and documenting the first pediatric cases of these variants in a Chinese cohort. Given the potential long-term risks and diagnostic complexity in asymptomatic pediatric patients, individualized surveillance and management strategies are warranted. Further research is needed to evaluate the functional consequences of novel mutations and their implications for pediatric hemostasis.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111064"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructive critique on the development and validation of a multiplex LC-MS/MS DBS assay","authors":"Parth Aphale,&nbsp;Shashank Dokania,&nbsp;Himanshu Shekhar","doi":"10.1016/j.clinbiochem.2025.111059","DOIUrl":"10.1016/j.clinbiochem.2025.111059","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111059"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of microcollection tube fill volume on common acute care tests","authors":"Fangze Cai ,&nbsp;Isolde Seiden-Long ,&nbsp;Allison A. Venner ,&nbsp;Heather Paul ,&nbsp;Jessica L. Gifford ,&nbsp;Tariq Roshan ,&nbsp;Lawrence de Koning","doi":"10.1016/j.clinbiochem.2025.111066","DOIUrl":"10.1016/j.clinbiochem.2025.111066","url":null,"abstract":"<div><h3>Background</h3><div>Microcollection tubes are frequently used in pediatric phlebotomy. We performed a pilot study to determine what clinical biochemistry and hematology tests can be reported on different microcollection tube fill volumes.</div></div><div><h3>Methods</h3><div>Blood was collected from 11 volunteers into Becton Dickinson (BD) Vacutainers® and microcollection tubes (BD Microtainers® and the Sarstedt Microvette® 300 FH) at different fill volumes (Filled: top line; Intermediate: second line; Short: third line. If there was no second or third line, 200 µL was used for short fills) for 36 clinical biochemistry tests and the complete blood count (CBC) with differential (23 components). At each fill volume, tests were strong candidates to report if they did not have statistically significant biases compared to results in Vacutainers®. Potential candidates had statistically significant biases that were small (median absolute bias &lt; 25 % of total allowable error and less than desirable bias from biological variation). Tests were not candidates if biases were significant and large (median absolute bias ≥ 25 % of TEa or ≥ desirable bias). Biases that increased or decreased across concentration ranges invalidated reporting candidacy.</div></div><div><h3>Results</h3><div>Twenty four clinical biochemistry tests were strong or potential candidates to report on all fill volumes, 7 were strong or potential candidates to report on some fill volumes and 5 were not candidates to report on any fill volumes. Seventeen CBC components were strong or potential candidates to report on all fill volumes, 2 were strong or potential candidates to report on some fill volumes and 4 were not candidates to report on any fill volumes.</div></div><div><h3>Conclusions</h3><div>While most tests were valid to report on different fill volumes, some were not. We encourage laboratories to perform their own studies on fill volumes.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111066"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the environmental impact paradox of clinical medical laboratories","authors":"Pernilla Sörme,&nbsp;Scott Weitze","doi":"10.1016/j.clinbiochem.2025.111063","DOIUrl":"10.1016/j.clinbiochem.2025.111063","url":null,"abstract":"<div><div>The global healthcare system is a substantial contributor to planetary greenhouse gas emissions and the climate crisis. Healthcare also has additional negative effects on the environment through the pollution of water, soil, and air, and the generation of general and regulated biomedical waste. The healthcare system’s lagging sustainability has both direct and indirect consequences for human health, these factors present a paradox. Healthcare Without Harm has estimated that global healthcare systems are emitting two gigatons of carbon dioxide yearly, accounting for 4.4% of total global net emissions. Healthcare systems should address their negative environmental impact, while still treating patients to the highest standards of care.</div><div>Laboratories are resource-intensive spaces and should be a principal consideration when addressing the overall sustainability strategy of a healthcare system. Clinical medical laboratories, in particular, have often not optimised operations for sustainability, and have overlooked carbon emissions. The last decade has seen slow adoption of sustainable practices in clinical diagnostic laboratories even though numerous tools and programs are available for implementation, a disappointing result that also suggests an opportunity for rapid and dramatic improvement.</div><div>This article will describe:<ul><li><span>•</span><span><div>The impact of clinical laboratories on the environment.</div></span></li><li><span>•</span><span><div>What actions clinical laboratories can take to reduce the environmental footprint of the healthcare system.</div></span></li><li><span>•</span><span><div>How third-party certification standards and established organizations are being utilized by hospitals and diagnostic laboratories.</div></span></li><li><span>•</span><span><div>Progress towards expanding the My Green Lab Certification framework to address the unique operational and environmental challenges of clinical laboratories.</div></span></li></ul></div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111063"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the indeterminate zone for the DiaSorin LIAISON H. Pylori stool antigen test","authors":"Natalia Volodko ,&nbsp;Mathew P. Estey ,&nbsp;Dustin Proctor ,&nbsp;Lily Olayinka ,&nbsp;Michelle L. Parker ,&nbsp;Ashley Newbigging ,&nbsp;Victoria Higgins","doi":"10.1016/j.clinbiochem.2025.111027","DOIUrl":"10.1016/j.clinbiochem.2025.111027","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Helicobacter pylori</em> (<em>H. pylori</em>) colonization increases the risk of upper gastrointestinal disorders and can be detected by various tests, including the stool antigen test (HpSAT). DiaSorin recommends an HpSAT equivocal/indeterminate zone of 0.90-&lt;1.10, but high variability observed in our laboratory prompted clinical implementation of a broader zone (0.60-&lt;1.80). This study aimed to define an optimal HpSAT indeterminate zone using molecular as reference and urea breath test (UBT) for confirmation.</div></div><div><h3>Materials and Methods</h3><div>HpSAT and stool molecular results were available from 379 patients, of which 52 had follow-up UBTs. HpSAT was analyzed by the LIAISON HpSAT assay (DiaSorin), UBT by isotope ratio mass spectrometry, and molecular testing by qPCR targeting <em>H. pylori</em> DNA. Logistic regression modeled HpSAT index values against PCR positivity to define an optimal indeterminate zone, supported by clinical performance and flagging rates analyses.</div></div><div><h3>Results</h3><div>Logistic regression determined an HpSAT index of 0.79 (95 % CI: 0.34–1.14) had 90 % probability of a negative PCR result, and 4.99 (4.09–6.63) had 90 % probability of a positive result, rounded to an indeterminate zone of 0.80-&lt;5.00. Lower thresholds assessed all had ≤ 2 % false negatives, while upper thresholds exhibited decreased false positive rates (22 % to 6 %) as thresholds increased (1.10 to 5.00), with minimal improvement beyond 3.00 (9 %). A modified zone of 0.80–&lt;3.00 offered high accuracy with 12.9 % indeterminate results (DiaSorin’s threshold: 2.8 %; laboratory’s current threshold: 13.1 %).</div></div><div><h3>Conclusions</h3><div>Our findings show that DiaSorin’s HpSAT indeterminate zone is too narrow to reliably distinguish true positive and negative results in clinical practice. A modified broader zone (0.80–&lt;3.00), derived via logistic regression using PCR as reference, improves diagnostic accuracy while minimizing indeterminate results.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111027"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel 17.9 kb deletion of the beta-globin gene causing beta-thalassemia trait in a Danish male","authors":"Helle Pilgaard Kristiansen ,&nbsp;Jesper Petersen ,&nbsp;Peter Schou ,&nbsp;Peter H. Nissen ,&nbsp;Anne Winther-Larsen","doi":"10.1016/j.clinbiochem.2025.111035","DOIUrl":"10.1016/j.clinbiochem.2025.111035","url":null,"abstract":"<div><h3>Background</h3><div>Beta-thalassemia is a common monogenic disease, especially in malaria-endemic areas. It is mainly caused by point mutations in the beta-globin gene (<em>HBB</em>) while large deletions are more rarely described. Here, a novel, large deletion encompassing the entire <em>HBB</em> gene causing beta-thalassemia in an ethnically Danish male is described.</div></div><div><h3>Case report</h3><div>A 60-year-old male with no family history of anemia was admitted to the local Department of Medicine with microcytotic anemia. He had observed fatigue and slight dizziness, but despite this, he felt healthy. His blood tests showed no signs of iron deficiency and a hemoglobinopathy was suspected. Hemoglobin fractionation by ion-exchange high-performance liquid chromatography revealed an elevated HbF of 5.9 % and an increased HbA2 of 8.5 %. GAP-PCR of the alpha-thalassemia <em>HBA1</em>/<em>HBA2</em> genes and Sanger sequencing of the <em>HBB</em> gene showed none of the common thalassemia-causing variations. Hence, multiplex ligation dependent probe amplification was performed and a deletion variant was identified that resulted in the complete loss of the <em>HBB</em> gene. The exact breakpoints were identified using Sanger sequencing, revealing a novel 17.9 kb deletion (NC000011.10:g.5211831_5229725del) not previously described in the literature or in databases. The deletion was consistent with beta-thalassemia trait in accordance with the patient’s symptoms.</div></div><div><h3>Conclusion</h3><div>We present a novel large deletion of the <em>HBB</em> gene causing beta-thalassemia trait detected in an ethnically Danish male. Thalassemia must be considered in patients with microcytosis of unknown cause despite a Northern European ethnicity.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111035"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}