Journal of Applied Laboratory Medicine最新文献

{"title":"Overcoming Platelet Aggregation Interference: Evaluation of the Complete Blood Count, Differential, and Reticulocyte (CDR) Mode on an Automated Analyzer for Accurate Platelet Counting.","authors":"Jia-le Gong, Qing Liao, Chao-Jun Duan, Zhouzhou FengHuang, Bo Zhang","doi":"10.1093/jalm/jfag092","DOIUrl":"https://doi.org/10.1093/jalm/jfag092","url":null,"abstract":"<p><strong>Background: </strong>This study assessed the ability of the complete blood count, differential, and reticulocyte (CDR) mode of the Mindray BC-6800 Plus analyzer to correct platelet aggregation by disaggregating platelets, evaluating how aggregation severity impacts accuracy to define an objective threshold for resampling.</p><p><strong>Methods: </strong>Agreement was assessed between CDR mode and the electrical impedance method for platelet counts in normal specimens using Pearson correlation, Passing-Bablok regression, and Bland-Altman analysis. The CDR mode's ability to correct false elevations caused by microcytes/fragments and false reductions caused by large platelets was evaluated by comparing CDR channel platelet count results (PLT-OF) with smear-estimated values (PLT-M) and fluorescence-method results (PLT-F). Disaggregation efficacy in aggregated samples was analyzed using the MC-80 digital morphology system. The optimal disaggregation threshold was determined by ROC analysis.</p><p><strong>Results: </strong>In normal specimens, PLT-OF showed a significant correlation with the electrical impedance-method platelet count results (PLT-I) (r = 0.999, P < 0.001). Passing-Bablok regression (PLT-I = 1.00 × PLT-OF) and Bland-Altman analysis demonstrated excellent agreement. For samples with PLT-I false abnormalities, the CDR mode effectively corrected both false elevations (due to microcytes/fragments) and false reductions (due to large platelets), showing no significant differences between PLT-OF and PLT-M or PLT-F (P > 0.05). In platelet-aggregated specimens, PLT-OF was significantly higher than PLT-I (P < 0.001). ROC analysis established 162 aggregates as the optimal threshold for effective disaggregation [area under the curve (AUC) = 0.776]. The dissociation rate was significantly greater in the mild vs severe-aggregation group (P = 0.004). Combining aggregate count with a PLT-OF to PLT-I difference (>115 × 109/L) improved prediction accuracy (AUC = 0.841).</p><p><strong>Conclusion: </strong>The CDR channel of the Mindray BC-6800 Plus analyzer effectively corrects spurious platelet counts.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Accuracy and Prognostic Value of the Dual GFAP/UCH-L1 Test in Patients Presenting to the Emergency Department with Mild Traumatic Brain Injury.","authors":"Miriam Menacho-Roman, Audrey Morales Rodríguez, José Roberto Penedo Alonso, Inés Pecharromán de Las Heras, Agustina Vicente Bartulos, Ignacio Arribas-Gómez","doi":"10.1093/jalm/jfag110","DOIUrl":"https://doi.org/10.1093/jalm/jfag110","url":null,"abstract":"<p><strong>Background: </strong>Excessive use of head computed tomography (CT) in mild traumatic brain injury (TBI) increases radiation exposure and contributes to emergency department crowding. Blood biomarkers glial fibrillary acid protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may improve risk stratification and guide clinical decision-making. We evaluated the diagnostic accuracy and prognostic value of a dual GFAP/UCH-L1 test, GFAP, and UCH-L1-individually and jointly-for detecting acute intracranial injury and predicting mortality.</p><p><strong>Methods: </strong>We conducted a retrospective observational study at a tertiary hospital from March 10, 2023, to March 31, 2025. Adult patients presenting within 12 h of mild TBI (Glasgow Coma Scale score 13 to 15) with available serum GFAP and UCH-L1 measurements were included. Biomarker concentrations were measured on the Alinity i. Dual GFAP/UCH-L1 test positivity was defined as GFAP ≥35 pg/mL and/or UCH-L1 ≥400 pg/mL. The primary outcome was acute intracranial injury on head CT. Diagnostic performance was assessed using CT as the reference standard. Secondary outcomes were 30- and 90-day mortality.</p><p><strong>Results: </strong>A total of 2932 patients were included (median age 83 years; 57% women). Intracranial injury was identified in 230 patients (7.8%). The dual GFAP/UCH-L1 test showed high sensitivity (97.4%) and negative predictive value (98.6%). GFAP demonstrated better discrimination (area under the receiver operating characteristic [ROC] curve [AUC] 0.768) than UCH-L1 (AUC 0.642) and GFAP + UCH-L1 (0.742). In multivariable analysis, dual GFAP/UCH-L1 test positivity (odds ratio [OR] 7.28) independently predicted intracranial injury. UCH-L1 was associated with 30 day (hazard ratio [HR] 1.00028) and 90-day mortality (HR 1.00022).</p><p><strong>Conclusions: </strong>The dual GFAP/UCH-L1 test provides strong rule-out accuracy for acute intracranial injury, while UCH-L1 offers meaningful prognostic information. Biomarker guided assessment may reduce unnecessary CT use and support early risk stratification in emergency care.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Plasma to Whole Blood: Validation of Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) As Accessible Biomarkers in Stroke.","authors":"Yuting Xue, Yinwei Gu, Jiajing Wu, Yufeng Sun, Xilong Wang, Jing Jin, Xiangyi Liu","doi":"10.1093/jalm/jfag113","DOIUrl":"https://doi.org/10.1093/jalm/jfag113","url":null,"abstract":"<p><strong>Background: </strong>Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are critical blood-based biomarkers for the diagnosis and monitoring of a wide range of central nervous system (CNS) injuries. Current plasma-based assays require centrifugation, which prolongs turnaround time (TAT) and limits utility in emergency settings. This study aimed to develop and validate a rapid, automated chemiluminescence immunoassay for the direct quantification of GFAP and NfL in whole blood.</p><p><strong>Methods: </strong>We used a dual-antibody sandwich chemiluminescence immunoassay to measure GFAP and NfL. The assay was optimized for whole blood through adjustments of reagent formulation and implementation of a hematocrit (HCT) correction algorithm. Performance was evaluated in terms of precision, linearity, limit of quantification, and interference. In total, 115 paired whole blood and plasma samples from 78 acute stroke patients were analyzed to assess diagnostic accuracy.</p><p><strong>Results: </strong>The HCT correction algorithm effectively minimized measurement bias across a wide HCT range (35%-55%). Precision of GFAP and NfL in whole blood and plasma showed coefficients of variation below 5% across a broad concentration range. Excellent correlations were observed between whole blood (HCT-corrected) and plasma measurements for both GFAP (R2 = 0.990) and NfL (R2 = 0.955). Diagnostic accuracy for distinguishing hemorrhagic from ischemic stroke was comparable between whole blood and plasma (AUC 0.86 vs 0.84, P = 0.58) in this population.</p><p><strong>Conclusions: </strong>The novel GFAP and NfL whole-blood assay, due to its shorter TAT, high consistency with plasma, and broad analytical range, demonstrated the potential to accelerate stroke triage in acute care settings.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting Friedewald-Substituted \"Direct\" LDL Cholesterol in a National Multi-Site Electronic Health Record Cohort: Prevalence and Benchmarking Impact.","authors":"Ronald Doku, Nana Yaw A Osafo, John Kwagyan, William M Southerland","doi":"10.1093/jalm/jfag098","DOIUrl":"10.1093/jalm/jfag098","url":null,"abstract":"<p><strong>Background: </strong>When LDL cholesterol (LDL-C) estimation equations are benchmarked against \"direct\" LDL-C (LDLdirect) values from electronic health records (EHRs), the implicit assumption is that reported direct values derive from chemical assays rather than from calculations. This assumption has not been systematically tested.</p><p><strong>Methods: </strong>We analyzed 19 470 same-day lipid panels from the All of Us Research Program (50+ health provider organizations). We defined the effective divisor, Deff = TG/(TC - HDL-C - LDLdirect), where TG is triglycerides and TC is total cholesterol, and tested for evidence that reported \"direct\" values were Friedewald-calculated (Deff ≈ 5.0), with validation on the National Health and Nutrition Examination Survey (NHANES) and the Medical Information Mart for Intensive Care IV (MIMIC-IV).</p><p><strong>Results: </strong>Of 19 470 panels (from All of Us), 7.6% (1482) were algebraically confirmed Friedewald-substituted (|LDLFW - LDLdirect| ≤ 0.02 mg/dL [0.0005 mmol/L], where LDLFW is the Friedewald-calculated LDL-C) and 31.1% met a broader criterion (≤ 0.5 mg/dL [0.013 mmol/L]). The Deff distribution showed a 27.6-fold spike at 5.0 (z = 68 vs empirical background; z = 263 vs shuffled-LDL null). Contamination deflated observed Friedewald mean absolute error (MAE) by 30.7% (11.85 vs 17.10 mg/dL [0.306 vs 0.442 mmol/L]; true MAE 44.3% higher). Near treatment thresholds, contamination masked 12 percentage points of misclassification among near-threshold cases at 70 mg/dL [1.81 mmol/L] (26% apparent vs 38% true). Within-patient discordance confirmed substitution (39.6-fold gap, P < 10⁻⁵). NHANES validation showed 28.3-fold enrichment. In MIMIC-IV, the spike was absent in measured panels (0.8×) but present in calculated panels (z = 210).</p><p><strong>Conclusions: </strong>A minimum of 7.6% of \"direct\" LDL-C values in this national multi-site EHR cohort are algebraically confirmed Friedewald-substituted (up to 31.1% under a broader criterion), deflating observed equation error and attenuating the apparent advantage of improved methods. Deff decontamination should be a standard preprocessing step for EHR-based equation benchmarking.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Patient Medians for Laboratory Quality Control Using Long-Term Carbamazepine Monitoring Data.","authors":"Anders Larsson, Mats B Eriksson, Emmanuel Bäckryd, Linda Steinholtz, Anna-Karin Hamberg","doi":"10.1093/jalm/jfag102","DOIUrl":"https://doi.org/10.1093/jalm/jfag102","url":null,"abstract":"<p><strong>Background: </strong>Carbamazepine is an antiepileptic and mood-stabilizing drug with complex pharmacokinetics and a narrow therapeutic index, making therapeutic drug monitoring (TDM) essential. The therapeutic reference range for carbamazepine at our laboratory is 20-40 µmol/L (4.7-9.4 mg/L). Long-term laboratory data may help identify population trends, seasonal or demographic variation, and the suitability of patient-derived medians as a quality-assurance tool.</p><p><strong>Methods: </strong>This retrospective study analyzed 12 577 serum carbamazepine results obtained between May 2007 and December 2025 at Uppsala University Hospital. The total number of unique individuals providing the test results was 3147. Demographic variables (age, sex) and sampling dates were included. Yearly percentiles were used to evaluate long-term trends, and monthly variation was assessed for seasonal effects. Equivalence of analytical results was examined during the transition from the Architect ci8200 to the Cobas Pro c503 platform (February 2021).</p><p><strong>Results: </strong>Annual test volume peaked in 2010 (n = 955) and declined to 160 by 2025. Despite reduced testing, carbamazepine concentrations increased steadily over time, with median values rising from 25.2 µmol/L (5.9 mg/L) in 2007 to 31.2 µmol/L (7.4 mg/L) in 2025. Seasonal analysis showed predictable drops in sampling during the Swedish summer vacation period but no meaningful variation in drug concentrations. The method transition in February 2021 showed strong agreement between platforms, with slightly higher values on the Cobas system (Cobas = 1.049 × Architect - 0.164; R2 = 0.946).</p><p><strong>Conclusions: </strong>Carbamazepine concentrations in routine patient samples have gradually increased over 2 decades, independent of declining test frequency. Seasonal workload fluctuations did not affect observed levels. Patient-derived medians were stable and sensitive to method changes, supporting their role as complementary internal quality-control tools. Long-term TDM databases provide valuable insights for both clinical interpretation and laboratory quality assurance.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148425517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on Severe Thrombocytopenia Complicating Iron Deficiency Anemia: A Diagnostic Challenge?","authors":"Olajumoke O Oladipo","doi":"10.1093/jalm/jfag104","DOIUrl":"https://doi.org/10.1093/jalm/jfag104","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Thrombocytopenia Complicating Iron Deficiency Anemia: A Diagnostic Challenge?","authors":"Lina Bahloul, Michelle Bedran, Catherine Trichet, Katell Peoc'h, Hana Manceau","doi":"10.1093/jalm/jfag080","DOIUrl":"https://doi.org/10.1093/jalm/jfag080","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden Figures of DNA. 1. June (Broomhead) Lindsey.","authors":"Thomas M Annesley","doi":"10.1093/jalm/jfag070","DOIUrl":"https://doi.org/10.1093/jalm/jfag070","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":"11 4","pages":"998-1000"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development, Validation, and Clinical Application of an HPLC-Based Method for Determining Adenosine Deaminase Activity in Adenosine Deaminase Deficiency-Severe Combined Immunodeficiency.","authors":"Maria Petrik, Evgeny Litvin, Andrey Osipyants, Aleksandra Filkova, Yulia Rodina, Dmitrii Blinov, Nikolay Grachev, Anna Shcherbina","doi":"10.1093/jalm/jfag037","DOIUrl":"10.1093/jalm/jfag037","url":null,"abstract":"<p><strong>Background: </strong>Adenosine deaminase (ADA) deficiency is a rare genetic condition leading to severe combined immunodeficiency. Timely and accurate quantification of ADA activity is crucial for both diagnosis and treatment monitoring. This study describes the development and analytical validation of a high-performance liquid chromatography (HPLC)-based method for measuring ADA activity in dried blood spot (DBS) samples.</p><p><strong>Methods: </strong>ADA activity was quantified by measuring the enzymatic conversion of adenosine to inosine and hypoxanthine, followed by chromatographic separation and detection. Method validation was conducted according to current bioanalytical guidelines and included assessment of selectivity, linearity, sensitivity, precision, trueness, extraction recovery, and stability. The study involved 3 groups of samples taken from healthy pediatric donors (n = 116), carriers of pathogenic mutations (n = 13), and patients with genetically confirmed ADA deficiency (n = 11).</p><p><strong>Results: </strong>The assay demonstrated high selectivity and linearity over the tested concentration ranges (coefficient of determination > 0.99 for both analytes). The lower limit of quantification was 0.312 μg/mL (2.29 μmol/L) for hypoxanthine and 0.5 μg/mL (1.86 μmol/L) for inosine. A reference interval for ADA activity in DBS was established at 14.94 to 43.28 nmol/h/mg. The mean ADA activity was 25.06 nmol/h/mg of protein in the control group, 14.08 nmol/h/mg in mutation carriers, and 2.18 nmol/h/mg in patients with ADA deficiency.</p><p><strong>Conclusions: </strong>The developed method allows precise and reliable determination of ADA activity in DBS. It can be applied for the diagnosis and monitoring of patients with ADA deficiency, as well as in scientific studies related to purine metabolism.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":"758-769"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective Removal of Calcium Dobesilate Interference in Triglyceride Measurement Using Copper Oxide.","authors":"Meng Zhao, Jiabao Fan, Panpan Lv, Zhengqi Zhu, Zhen Zhao","doi":"10.1093/jalm/jfag011","DOIUrl":"10.1093/jalm/jfag011","url":null,"abstract":"<p><strong>Background: </strong>Calcium dobesilate (CD), a vasoprotective drug, has been reported to cause substantial negative interference in enzymatic triglyceride (TG) assays, compromising result accuracy. This study aimed to quantify the extent of CD-induced bias in TG measurement and to evaluate whether copper oxide (CuO) pretreatment could effectively eliminate this interference.</p><p><strong>Methods: </strong>Serum samples with TG concentrations of 1.76 and 5.61 mmol/L (156 mg/dL and 497 mg/dL) were spiked with CD at 2-64 μg/mL and analyzed on the Roche cobas c701 system. To assess the corrective capability of CuO, 0.1 g of CuO was added prior to measurement. Percentage biases in TG results, with and without CuO pretreatment, were compared to evaluate interference and correction efficiency.</p><p><strong>Results: </strong>CD markedly reduced TG measurement values, particularly at lower TG concentrations, resulting in biases exceeding the clinically acceptable limit. When the TG concentration was 1.76 mmol/L (156 mg/dL), the addition of 0.1 g CuO decreased CD-induced biases from -0.56% to -0.18%, -2.45% to -0.36%, -5.49% to -0.15%, -8.96% to -1.84%, -16.65% to 0.41%, and -29.79% to -2.27%, respectively, at CD concentrations of 2, 4, 8, 16, 32, and 64 μg/mL. A similar correction was observed at 5.61 mmol/L TG (497 mg/dL), where biases were reduced from -0.93% to -0.45%, -1.98% to 1.00%, -2.97% to -2.13%, -4.71% to -2.18%, -12.16% to -1.79%, and -17.92% to -0.65%, respectively.</p><p><strong>Conclusions: </strong>CuO pretreatment effectively mitigates CD-induced negative interference in enzymatic TG assays, restoring measurement accuracy. This simple, low cost, and clinically practical approach provides a reliable solution for accurate TG monitoring in patients receiving CD therapy.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":"798-805"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}