Lydia Delphin, Mercy Prasanna, Aswitha Ganesan, N T Varatharajan, Debdatta Basu
{"title":"Pseudolymphocytosis on Impedance Counters-The Need for Morphological Correlation on Peripheral Smear Examination.","authors":"Lydia Delphin, Mercy Prasanna, Aswitha Ganesan, N T Varatharajan, Debdatta Basu","doi":"10.1111/ijlh.70106","DOIUrl":"10.1111/ijlh.70106","url":null,"abstract":"","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"1218-1220"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thrombotic Microangiopathy Without Thrombocytopenia as a Manifestation of Hypertensive Emergency.","authors":"Hana F Ahmad, Gautham H Budaraju, Monish A Sheth","doi":"10.1111/ijlh.70149","DOIUrl":"10.1111/ijlh.70149","url":null,"abstract":"","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"1258-1260"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiara Novelli, Arianna Gatti, Flora Ierna, Elena Riccardi, Irene Cuppari
{"title":"Design and Implementation of an Automated Interpretation Algorithm for Lupus Anticoagulant Functional Testing.","authors":"Chiara Novelli, Arianna Gatti, Flora Ierna, Elena Riccardi, Irene Cuppari","doi":"10.1111/ijlh.70153","DOIUrl":"10.1111/ijlh.70153","url":null,"abstract":"<p><strong>Introduction: </strong>Lupus anticoagulant (LA) testing is essential, albeit complex, in the laboratory diagnosis of antiphospholipid syndrome (APS). Given the multi-step workflow and the variability introduced by anticoagulant therapy, reagent differences, and interpretive approaches, result interpretation requires expert evaluation. To address these challenges, we implemented a middleware-based automated algorithm in our four-hospital institution using the HemoHub system, guided by the latest ISTH recommendations. The objectives were to automate reflex testing, standardize interpretation, and support clinical decision-making.</p><p><strong>Methods: </strong>The algorithm incorporated rules aligned with good laboratory practice for LA diagnostics, including reflex testing, result interpretation, internal comments, integration of historical data, and auto-validation of negative cases. Retrospective validation was performed on 190 historical cases in which the diagnosis was made conventionally and corroborated by follow-up data. A subsequent prospective blind comparison with manual operator-based workflow was conducted on 481 routine samples.</p><p><strong>Results: </strong>Concordance between automated and manual interpretations reached 100% for LA negative and positive cases, with slightly lower agreement for first-time positives (88.6% and 82.4%). When automated interpretation was not assignable, the system still provided useful internal comments. Additionally, 58.4% of samples were auto-validated, significantly reducing manual workload. Time comparison demonstrated substantial savings for both experienced and less-experienced pathologists.</p><p><strong>Conclusion: </strong>The implementation of the automated algorithm improved consistency, reduced interpretation time, and minimized intra- and inter-laboratory variability. By integrating clinical context and historical data, it enhanced diagnostic accuracy. These findings support the use of middleware-based, rule-driven interpretation as a reliable and efficient approach to standardizing LA testing and optimizing laboratory workflow.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"1181-1188"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hamide Albayrak, Mustafa Ertan Ay, Anıl Tombak, Kenan Çevik, Özlem İzci Ay, Tuba Kabasakal, Mehmet Emin Erdal
{"title":"Circadian Deregulation in Multiple Myeloma: BMAL1/CLOCK Expression Patterns and Diagnostic Performance.","authors":"Hamide Albayrak, Mustafa Ertan Ay, Anıl Tombak, Kenan Çevik, Özlem İzci Ay, Tuba Kabasakal, Mehmet Emin Erdal","doi":"10.1111/ijlh.70154","DOIUrl":"10.1111/ijlh.70154","url":null,"abstract":"<p><strong>Background: </strong>Circadian clock disruption has emerged as a relevant axis in cancer; however, the expression patterns and diagnostic relevance of BMAL1 and CLOCK in multiple myeloma (MM) remain insufficiently defined.</p><p><strong>Methods: </strong>BMAL1 and CLOCK mRNA expression was quantified by RT-qPCR in bone marrow samples from 46 newly diagnosed MM patients and 13 healthy controls. Group comparisons, ROC analyses, multivariate logistic regression, partial correlation, and machine-learning models (logistic regression, random forest, and support-vector machine) with stratified 5-fold cross-validation (including class-weighted sensitivity analysis) were performed.</p><p><strong>Results: </strong>BMAL1 expression was significantly higher in MM than in controls (1.12 ± 0.33 vs. 0.85 ± 0.33, p = 0.016; Cohen's d = 0.83), whereas CLOCK showed no significant univariate difference (p > 0.2). BMAL1 demonstrated moderate diagnostic performance (AUC = 0.729), while CLOCK alone showed limited discrimination (AUC = 0.617). Combined analysis modestly improved performance (AUC = 0.756). In multivariate logistic regression, BMAL1 remained a strong independent predictor of MM (OR = 3343.4, p = 0.0046), whereas CLOCK showed an inverse adjusted association (OR = 0.0037, p = 0.019). BMAL1 and CLOCK expression were strongly correlated in MM (ρ ≈ 0.80), persisting after adjustment for age, ISS stage, and β2-microglobulin (partial r = 0.847, p = 2.2 × 10-13). Among classifiers, the random forest achieved the best performance (AUC = 0.832; AUPRC = 0.952). Specificity was limited across classifiers, indicating that these performance estimates are exploratory and require validation in larger cohorts.</p><p><strong>Conclusion: </strong>MM is characterized by BMAL1 upregulation within a preserved but imbalanced BMAL1/CLOCK axis rather than uniform shifts across circadian genes. Although diagnostic performance is moderate, consistent signals across statistical and machine-learning approaches support an MM-associated circadian expression pattern warranting further validation.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"1123-1132"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapid Centrifugation for Coagulation Testing: A Multianalyzer Validation Study Harmonizing Preanalytical Protocols for Total Laboratory Automation.","authors":"Orakan Limpornpugdee, Jirapa Kaewkhruawan, Pitchayaporn Riyagoon, Waroonkarn Laiklang, Wararat Masalae, Surapat Tanticharoenkarn, Kwanlada Chaiwong, Phongsapak Pipatnavakij, Parinda Limprasert, Chutitorn Ketloy, Eakachai Prompetchara","doi":"10.1111/ijlh.70188","DOIUrl":"10.1111/ijlh.70188","url":null,"abstract":"<p><strong>Objectives: </strong>Centrifugation requirements differ between coagulation and clinical chemistry testing, potentially limiting workflow efficiency and total laboratory automation (TLA). Coagulation assays typically require standard centrifugation at 1500 g for 15 min, whereas chemistry samples use a rapid protocol at 2300 g for 5 min. This study evaluated the impact of rapid centrifugation on prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer results.</p><p><strong>Methods: </strong>Blood samples were prospectively collected from volunteers in 3, 2, and pediatric 1 mL citrate tubes and were processed using standard or rapid centrifugation. Testing was performed for PT, APTT, and D-Dimer on Sysmex CN3000 and ACL-TOP 750 analyzers, with residual platelet counts assessed.</p><p><strong>Results: </strong>A total of 130 samples were analyzed (41 from 3 mL tubes, 41 from 2 mL tubes, and 39 from 1 mL tubes). Rapid centrifugation produced significantly higher residual platelet counts than the standard protocol (39.2 × 10<sup>9</sup>/L vs. 18.8 × 10<sup>9</sup>/L, p < 0.0001). Strong correlations (r > 0.9) were observed for PT and APTT across analyzers, while D-dimer results on ACL-TOP 750 showed slightly lower correlation (r = 0.830). Bland-Altman analysis demonstrated small mean biases (< 1% for PT and APTT). D-dimer biases from CN3000 and ACL-TOP 750 were 1.06% and -2.70%, respectively, which remained within the predefined total allowable error. Residual platelets showed no impact on test results.</p><p><strong>Conclusions: </strong>Rapid centrifugation at 2300 g for 5 min provides coagulation results comparable to the standard protocol and may facilitate integration of coagulation testing into TLA workflows.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"1201-1210"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimization of Analytical Performances and Routine Laboratory Implementation of NPM1 Mutation Detection by Digital PCR in the Diagnosis and Monitoring of NPM1 -Mutated Acute Myeloid Leukemias.","authors":"Chloé Ferrari, Brice Coulleray, Pauline Kerneves, Carole Geara, Dina Naguib, Guénaelle Levallet, Elizabeth Battersby, Sylvain Chantepie, Yohann Repessé, Coralie Nectoux, Elsa Maitre","doi":"10.1111/ijlh.70161","DOIUrl":"10.1111/ijlh.70161","url":null,"abstract":"<p><strong>Introduction: </strong>Quantification and monitoring of NPM1 mutations represent a key tool in the management of acute myeloid leukemia (AML), offering strong prognostic value and serving as a marker of minimal residual disease (MRD). Digital PCR (dPCR) provides absolute quantification with high sensitivity and specificity, offering advantages over conventional qPCR-based methods, particularly for rare or atypical NPM1 mutations.</p><p><strong>Methods: </strong>We adapted and evaluated a digital PCR strategy including both monoplex and multiplex assays targeting the most common NPM1 mutations (types A, B, D) as well as rare variants. A touch-down PCR protocol was optimized to harmonize the dPCR protocol and enhance specificity. Assay performance was evaluated in terms of limit of detection (LoD), limit of quantification (LoQ), linearity, and specificity, and compared to quantitative PCR (qPCR).</p><p><strong>Results: </strong>The multiplex dPCR assay allowed detection of all clinically relevant NPM1 mutations with an LoD of 0.01%, while monoplex type A, B and D assays reached 0.001% for type A, B and D. The method showed strong linearity (R <sup>2</sup> > 0.99 for all targets) and high concordance with qPCR (R<sup>2</sup> = 0.9967). In patient samples, dPCR demonstrated improved sensitivity over qPCR, detecting low-level NPM1 mutations in samples previously negative by qPCR, and enabled early relapse detection.</p><p><strong>Conclusion: </strong>The approach enabled early relapse prediction in selected patients and improved molecular follow-up, even for rare NPM1 mutations not covered by standard qPCR panels. It simplifies laboratory routine and improves MRD assessment, according to current ELN guidelines and the growing need for personalized molecular monitoring in AML.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"1149-1157"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diego Velasco-Rodríguez, María Marcos-Jubilar, Inés Martínez-Alfonzo, Laura Martos, Carlos Aguilar, Noelia Vilalta, Dolors Llobet, Ana Marco-Rico, David Aragoneses, Pascual Marco, Luciana Ricca, David Ferreira, Sara Lopes, João Mariano-Pego, Ángel Bernardo, Antonio Moscardó, Santiago Bonanad, Susana Gassiot, Isabel Gutiérrez-Jomarrón, Jose Antonio Páramo, Pilar Llamas-Sillero, Joan Carles Reverter
{"title":"Multicenter Interlaboratory Study of Thrombin Generation Assay in Healthy Adults Using the ST Genesia Analyzer With the STG-ThromboScreen Reagent (With and Without Thrombomodulin).","authors":"Diego Velasco-Rodríguez, María Marcos-Jubilar, Inés Martínez-Alfonzo, Laura Martos, Carlos Aguilar, Noelia Vilalta, Dolors Llobet, Ana Marco-Rico, David Aragoneses, Pascual Marco, Luciana Ricca, David Ferreira, Sara Lopes, João Mariano-Pego, Ángel Bernardo, Antonio Moscardó, Santiago Bonanad, Susana Gassiot, Isabel Gutiérrez-Jomarrón, Jose Antonio Páramo, Pilar Llamas-Sillero, Joan Carles Reverter","doi":"10.1111/ijlh.70168","DOIUrl":"10.1111/ijlh.70168","url":null,"abstract":"<p><strong>Introduction: </strong>Fully automated thrombin generation (TG) assays facilitate the transition from research to clinical application. We conducted a multicenter inter-laboratory study using the ST Genesia analyzer to evaluate assay performance and establish reference intervals in healthy adults from Spain and Portugal.</p><p><strong>Methods: </strong>In this multicenter study, plasma samples from healthy adult volunteers were analyzed across 12 laboratories following a harmonized protocol. TG was measured using the STG-ThromboScreen reagent in the presence and absence of thrombomodulin (TM). Analytical performance and reference intervals were assessed.</p><p><strong>Results: </strong>Within-run and intra-day precision were excellent (coefficient of variation < 10%) for all TG parameters except velocity index. Normalization reduced interlaboratory variability for amplitude-based parameters such as endogenous thrombin potential (ETP) and peak height, whereas its effect was less pronounced for velocity index. Satisfactory interlaboratory performance (|z| ≤ 2) was achieved in 96%-98% of results, and normalized parameters showed minimal bias across centers. In 252 healthy adults, median normalized values were: ETP 131% (IQR 118-142), peak height 116% (IQR 104-127), lag time 2.6 min (IQR 2.3-2.8), and time-to-peak 5.5 min (IQR 5.0-5.9). Median ETP inhibition in the presence of TM was 47.2% (IQR 35.1-61.8). Age had a modest influence on TG parameters, whereas sex differences were observed.</p><p><strong>Conclusions: </strong>This multicenter interlaboratory study in the Iberian Peninsula demonstrates high reproducibility of TG measurement using the ST Genesia platform with the STG-ThromboScreen reagent. These findings support its use for standardized TG assessment and provide reference intervals for clinical and research settings.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"1189-1200"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}