International journal of laboratory hematology最新文献

{"title":"How Trustworthy is Light Transmittance Platelet Aggregometry With Low Platelet Count Samples? Insights From Test Replicates and Retrospective Analysis of Several Decades of Diagnostic Samples.","authors":"Catherine P M Hayward, Rabab Al Dawood, Lindsay Wice, Karen A Moffat","doi":"10.1111/ijlh.14518","DOIUrl":"https://doi.org/10.1111/ijlh.14518","url":null,"abstract":"<p><strong>Introduction: </strong>Light transmission platelet aggregometry (LTA) is useful to diagnose platelet function disorders (PFD). We evaluated the precision and reproducibility of LTA with low platelet count platelet-rich plasma (LPRP).</p><p><strong>Methods: </strong>LPRP maximal aggregation (MA) precision for informative agonists and LTA reproducibility were assessed using multiple replicates for adjusted control LPRP (CLPRP) and retrospective analysis of several decades of consecutive patient LPRP (PLPRP) and CLPRP tests with replicates between and/or within tests.</p><p><strong>Results: </strong>Intra-subject CLPRP had acceptable MA CVs and tracings unless platelets were ≤ 25 × 10⁹/L. Among tests with replicates, PLPRP with ≤ 25 × 10⁹ platelets/L were uncommon (6/247 samples) and 5/6 showed pathognomonic Bernard-Soulier syndrome (BSS) findings. Among evaluated patients (n = 195; diverse diagnoses), 44.6% had abnormal LTA findings on ≥ 1 tests after excluding single, within-test MA outliers in 21/194 PLPRP and 2/27 CLPRP tests. Median, intra-subject, within-test coefficients of variation (CVs) for PLPRP and CLPRP MA responses to informative agonists were acceptable for most agonists, with higher CV for 0.5 mg/mL ristocetin, weak agonists, and impaired responses, and only small differences between MA estimates across agonists. Between-test agreement was good for MA responses, with 80.5% of patients and 98.1% of controls having consistent overall LTA findings, with significantly more patients than controls having consistently abnormal LTA findings (46.3% vs. 0%; p < 0.001).</p><p><strong>Conclusions: </strong>Diagnostic LTA with LPRP has acceptable precision and reproducibility when evaluated with informative agonists. Nonetheless, caution is warranted when testing samples with ≤ 25 × 10⁹ platelets/L, which often show BSS findings.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478276","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":"Molecular Testing in Sickle Cell Disease: From Newborn Screening to Transfusion Care.","authors":"Thomas Pincez, Yves D Pastore","doi":"10.1111/ijlh.14513","DOIUrl":"https://doi.org/10.1111/ijlh.14513","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is one of the most frequent monogenic diseases worldwide and a highly heterogeneous and complex disease. SCD care carries several challenges. This includes early and accurate diagnosis as well as optimal red blood cell transfusion matching in this population carrying a high risk of alloimmunization. For decades, molecular biology has used hemoglobin and SCD as models for the development of several molecular tools. Such tools can now be used for various aspects of SCD care. Molecular diagnosis is notably the root of noninvasive prenatal testing. In postnatal diagnosis, including newborn screening, molecular approaches can overcome several limitations of protein-based methods. Simple approaches such as polymerase chain reaction can be used as a high-throughput and low-cost screening test. Moreover, combining sequence and deletion analyses allows for a comprehensive study of the β-globin locus, resolving complex cases. In transfusion care, genotyping for blood group determination has been shown to be more accurate compared to protein-based serological testing. Future development of molecular testing in SCD includes their use as prognostic tools and recent molecular diagnosis approaches. However, despite carrying major advantages, molecular testing may also present some limitations, such as high cost, limited accessibility in many countries, and limited information using targeted approaches. Molecular testing has a different pattern of advantages and limitations than protein-based analyses. Therefore, the optimal use of molecular testing is frequently not as a standalone approach but in combination with protein-based techniques. The optimal combination depends on the resources available and the clinical challenge, to ultimately improve SCD care.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304105","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":"Effects of Artificial Lung and Roller Pump on Platelet Morphology and Activation During Simulated Extracorporeal Circulation.","authors":"Hohomi Arao, Yukinori Kozuma, Tatsuya Furugaki, Tatsuya Kawaguchi, Kazumi Matsushima-Nagata, Ippei Noboruo, Hiroshi Kojima, Yuji Hiramatsu, Yasuyuki Suzuki","doi":"10.1111/ijlh.14514","DOIUrl":"https://doi.org/10.1111/ijlh.14514","url":null,"abstract":"<p><strong>Introduction: </strong>Prolonged extracorporeal circulation time is known to cause intraoperative and postoperative bleeding, but the underlying mechanism is not fully understood. In this study, we analyzed the effects of artificial lung and roller pump on platelet morphology and activation using a simulated extracorporeal circulatory circuit.</p><p><strong>Methods: </strong>Blood was drawn from healthy volunteers in the presence of unfractionated heparin as an anticoagulant and recirculated for 180 min at 0.75 L/min with the circuit under a room temperature. After the samples were collected, platelet counts, platelet surface markers, and platelet activation markers were measured.</p><p><strong>Results: </strong>When whole blood was circulated for 180 min, platelet counts, platelet sizes, and expressions of glycoprotein Ibα (CD42b) and glycoprotein IIb (CD41) significantly decreased after recirculation. In addition, dense bodies and α-granules within platelets were also reduced after recirculation. Adhesion to collagen and platelet aggregation were significantly reduced after recirculation compared to pro-circulation. When platelets were stimulated with A23187 pro- and post-extracorporeal circulation, the expression of P-selectin was significantly lower in CD42b^- platelets than in CD42b⁺ platelets. On the other hand, phosphatidylserine (PS) exposure in CD42b^- platelets was higher than in CD42b⁺ platelets with or without stimulation.</p><p><strong>Conclusion: </strong>It was suggested that artificial lungs and roller pumps may reduce platelet activity by causing cleavage of platelet membrane glycoproteins and release of granules within platelets.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277140","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":"RBPJ/PAF1 Signaling Axis Promotes Cloning Expansion in Paroxysmal Nocturnal Hemoglobinuria Through NOTCH Signaling.","authors":"Liyan Li, Junshu Wu, Zewei Chen, Hui Liu, Zhaoyun Liu, Yingying Chen, Honglei Wang, Rong Fu","doi":"10.1111/ijlh.14512","DOIUrl":"https://doi.org/10.1111/ijlh.14512","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH) is closely related to additional somatic mutations besides PIG-A. Our previous research showed that some PNH patients had a high frequency mutation of RBPJ through whole genome exon sequencing, which played an important role in the pathogenesis of PNH, but its molecular mechanism is still unclear.</p><p><strong>Methods: </strong>SiRNA transfection was employed to generate RBPJ-knockdown K562 and PNH cell lines. Cell proliferation and apoptosis were assessed via EDU and flow cytometry, respectively. LC-MS following silver staining identified RBPJ-interacting proteins, which were subsequently validated using CO-IP and gradient expression analysis. Western blot examined the relationship between RBPJ, PAF1, and the NOTCH signaling pathway in low-RBPJ-expressing PNH cell lines. The correlation between PAF1 expression, clonal PNH, and RBPJ expression was also analyzed.</p><p><strong>Results: </strong>Knocking Out RBPJ Leads to Reduced Cell Proliferation and Increased Apoptosis in PNH Cells. We Identified PAF1 as an Interacting Protein of RBPJ and Confirmed the Interaction Domain to Be the BTD Domain of RBPJ. Knocking Out RBPJ Resulted in a Decrease of PAF1 Protein in KO Cell Lines, While the NOTCH1 and HEY1 Protein Expression Related to the NOTCH Signaling Decreased. GSEA Demonstrated That the KO Cell Lines Exhibited a Decreased NOTCH Signaling Pathway Upon PAF1 Downregulation. Knocking Down PAF1 Results in Reduced Protein Levels of NOTCH1 and NOTCH2. Subsequently, After Knocking Out RBPJ With PAF1 Overexpression, NOTCH1 Expression Was Restored, Cell Apoptosis Rate Decreased, and Cell Proliferation Increased. Subsequently, we Observed Elevated PAF1 Expression in PNH Patients, Which Positively Correlated With the FLAER-CD14, FLAER-CD24 and RBPJ mRNA Expression in PNH Patients.</p><p><strong>Conclusion: </strong>RBPJ/PAF1 may promote PNH clone proliferation by regulating the NOTCH signaling pathway.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277141","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":"Lupus Anticoagulant Testing in Challenging Situations: Navigating Complexities.","authors":"Katrien M J Devreese","doi":"10.1111/ijlh.14490","DOIUrl":"https://doi.org/10.1111/ijlh.14490","url":null,"abstract":"<p><p>The laboratory diagnosis of antiphospholipid syndrome (APS) relies on detecting persistent antiphospholipid antibodies (aPL), including lupus anticoagulant (LA) as one of the three laboratory criteria. LA is a well-established risk factor in APS and the cornerstone of APS diagnosis, identifying triple-positive patients. LA testing is supported by testing guidelines, but challenges remain with LA measurement, which is complex and susceptible to numerous pitfalls and interferences. A nuanced understanding of the technical and interpretative aspects of LA testing is crucial for accurate diagnosis. Limited to specific patient populations, the timing of testing in relation to clinical events is essential to avoid false results, and only persistent LA positivity is considered diagnostic. Proper sample preparation, choice of assays, test procedure, cutoff values, and strategies to handle anticoagulant therapy interference pose significant challenges in LA testing. While advances in the harmonization of test procedures and testing guidelines have improved diagnostic reliability, the complex nature of LA demands careful consideration of methodological issues and potential interferences, underscoring the importance of expertise and interdisciplinary communication in achieving accurate results. Interpretative comments and close interaction between clinical pathologists and clinicians are mandatory for diagnosis and patient management. This paper will focus on the technical aspects of the laboratory method and the interpretation of LA results in the diagnosis of APS with attention to specific situations where LA testing is difficult.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082878","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":"Classification of Platelet-Activating Anti-Platelet Factor 4 Disorders.","authors":"Theodore E Warkentin","doi":"10.1111/ijlh.14486","DOIUrl":"https://doi.org/10.1111/ijlh.14486","url":null,"abstract":"<p><strong>Introduction: </strong>The prototypic anti-platelet factor 4 (PF4) disorder-heparin-induced thrombocytopenia and thrombosis (HITT)-features immunoglobulin G (IgG) class antibodies that activate platelets, monocytes, and neutrophils in a mainly heparin-dependent fashion via Fcγ receptor-dependent cellular activation. The identification in 2021 of an ultrarare HITT-mimicking disorder, vaccine-induced immune thrombocytopenia and thrombosis (VITT)-triggered by two different adenoviral vector vaccines-abruptly broadened the spectrum of recognized anti-PF4 disorders.</p><p><strong>Objective: </strong>To classify platelet-activating anti-PF4 disorders, both HITT/HITT-like and VITT/VITT-like.</p><p><strong>Methods: </strong>Literature was reviewed from the perspective of a researcher-clinician involved in identifying novel anti-PF4 disorders.</p><p><strong>Results: </strong>Atypical presentations of HITT with proximate heparin triggers but which evince heparin-independent platelet-activating properties (\"autoimmune HITT\") have been recognized since 2001; heparin-independent platelet-activating properties also characterize HITT-mimicking disorders with undefined non-heparin triggers (e.g., post-knee replacement \"spontaneous HITT\"). Antibodies identical to those of (vaccine-induced) VITT can rarely be triggered by natural adenovirus infection. HITT and VITT antibodies recognize different epitopes on PF4. All the aforementioned anti-PF4 disorders are acute, transient, and self-limited. Recently, however, chronic anti-PF4 disorders featuring potent VITT-like properties of monoclonal proteins (M-proteins) have been identified: this oftentimes treatment-refractory entity, named \"VITT-like monoclonal gammopathy of thrombotic significance\" (VITT-like MGTS), dramatically expands the clinical spectrum of recognized anti-PF4 disorders. Anti-PF4 disorders with heparin-independent platelet-activating antibodies, whether HITT or VITT, may require management strategies beyond anticoagulation alone, including high-dose intravenous immunoglobulin (IVIG) or (for VITT-like MGTS) the Bruton's tyrosine kinase inhibitor, ibrutinib.</p><p><strong>Conclusion: </strong>Clinicians and laboratorians require knowledge of the rapidly broadening spectrum of recognized acute and chronic anti-PF4 disorders.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000865","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":"Preface.","authors":"Ian Mackie, Giuseppe d'Onofrio","doi":"10.1111/ijlh.14494","DOIUrl":"https://doi.org/10.1111/ijlh.14494","url":null,"abstract":"","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029478","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":"Developments in the International Journal of Laboratory Hematology.","authors":"Ian Mackie, Giuseppe d'Onofrio","doi":"10.1111/ijlh.14493","DOIUrl":"https://doi.org/10.1111/ijlh.14493","url":null,"abstract":"","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056002","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":"Measuring Direct Oral Anticoagulant (DOAC) Levels: Applications, Limitations, and Future Directions.","authors":"Siraj Mithoowani, Chee Wee Tan, Deborah M Siegal","doi":"10.1111/ijlh.14483","DOIUrl":"https://doi.org/10.1111/ijlh.14483","url":null,"abstract":"<p><strong>Introduction: </strong>There are important challenges with the measurement and interpretation of direct oral anticoagulant (DOAC) anticoagulant effect including a lack of therapeutic ranges, inaccuracy of routinely available coagulation assays, lack of established thresholds for clinically significant effect, and uncertainty about how to apply the results to patient care.</p><p><strong>Objective: </strong>In this narrative review, we provide a practical approach to DOAC measurement in clinical practice.</p><p><strong>Methods: </strong>By summarizing the literature and using illustrative cases, we highlight key principles of commonly available tests, outline potential indications for measuring DOAC drug levels, and provide guidance on interpreting results to inform management decisions.</p><p><strong>Conclusion: </strong>While DOACs do not require routine monitoring of anticoagulant effect, assessment of plasma DOAC concentration may be helpful in select emergency and non-emergency clinical scenarios.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002761","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":"Making Molecular Diagnostics Faster.","authors":"Carl T Wittwer, Luming Zhou, Felix Ye, Adam Millington, Adrian de Cola, Noriko Kusukawa","doi":"10.1111/ijlh.14487","DOIUrl":"10.1111/ijlh.14487","url":null,"abstract":"<p><strong>Background: </strong>Over the past 40 years, molecular diagnostic methods have evolved from multi-step, time-consuming protocols towards either rapid targeted tests or expansive, massively parallel testing.</p><p><strong>Aims: </strong>Here we consider the speed limits of targeted molecular diagnostics, considering the three sequential required steps: nucleic acid preparation, amplification, and analysis.</p><p><strong>Materials & methods: </strong>Instead of the bind/wash/elute steps commonly used for nucleic acid extraction, simple alkaline lysis of whole blood results in a suspension ready for PCR in seconds that can be added directly to an appropriately buffered PCR master mix. For amplification, the time requirements of PCR are typically limited by the temperature cycling instrumentation and not by biochemistry.</p><p><strong>Results & discussion: </strong>By lowering sample volumes, increasing the surface area to volume ratio, decreasing the thickness of the sample container, decreasing the amplicon size, and inducing rapid temperature changes by a myriad of innovative means, 30 cycles of PCR can easily be completed in less than 5 min. By increasing primer and polymerase concentrations in synchrony with even faster cycling (< 2 s cycles), \"extreme PCR\" has amplified a 60 bp human genomic target in < 15 s (35 cycles) with high yield and specificity. For analysis, cumbersome, contamination-prone gel analysis can be replaced by melting curve analysis. Although melting curve analysis usually takes up to an hour on commercial instrumentation, precise temperature control can enable single base genotyping in 1-4 s.</p><p><strong>Conclusion: </strong>These advances demonstrate the feasibility of sample-to-answer molecular diagnostics in seconds.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012377","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}