Transfusion Medicine and Hemotherapy最新文献

{"title":"Circulating Iron in Patients with Sickle Cell Disease Mediates the Release of Neutrophil Extracellular Traps.","authors":"Kristof Van Avondt,&nbsp;Marein Schimmel,&nbsp;Ingrid Bulder,&nbsp;Gerard van Mierlo,&nbsp;Erfan Nur,&nbsp;Robin van Bruggen,&nbsp;Bart J Biemond,&nbsp;Brenda M Luken,&nbsp;Sacha Zeerleder","doi":"10.1159/000526760","DOIUrl":"https://doi.org/10.1159/000526760","url":null,"abstract":"<p><strong>Introduction: </strong>Neutrophils promote chronic inflammation and release neutrophil extracellular traps (NETs) that can drive inflammatory responses. Inflammation influences progression of sickle cell disease (SCD), and a role for NETs has been suggested in the onset of vaso-occlusive crisis (VOC). We aimed to identify factors in the circulation of these patients that provoke NET release, with a focus on triggers associated with hemolysis.</p><p><strong>Methods: </strong>Paired serum and plasma samples during VOC and steady state of 18 SCD patients (HbSS/HbSβ⁰-thal and HbSC/HbSβ⁺-thal) were collected. Cell-free heme, hemopexin, and labile plasma iron have been measured in the plasma samples of the SCD patients. NETs formation by human neutrophils from healthy donors induced by serum of SCD patients was studied using confocal microscopy and staining for extracellular DNA using Sytox, followed by quantification of surface coverage using ImageJ.</p><p><strong>Results: </strong>Eighteen patients paired samples obtained during VOC and steady state were available (11 HbSS/HbSβ⁰-thal and 7 HbSC/HbSβ⁺-thal). We observed high levels of systemic heme and iron, concomitant with low levels of the heme-scavenger hemopexin in sera of patients with SCD, both during VOC and in steady state. In our in vitro experiments, neutrophils released NETs when exposed to sera from SCD patients. The release of NETs was associated with high levels of circulating iron in these sera. Although hemin triggered NET formation in vitro, addition of hemopexin to scavenge heme did not suppress NET release in SCD sera. By contrast, the iron scavengers deferoxamine and apotransferrin attenuated NET formation in a significant proportion of SCD sera.</p><p><strong>Discussion: </strong>Our results suggest that redox-active iron in the circulation of non-transfusion-dependent SCD patients activates neutrophils to release NETs, and hence, exerts a direct pro-inflammatory effect. Thus, we propose that chelation of iron requires further investigation as a therapeutic strategy in SCD.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"321-329"},"PeriodicalIF":2.2,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/b0/tmh-0050-0321.PMC10521246.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41130382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Individual Patient Platelet Demand in a Large Tertiary Care Hospital Using Machine Learning.","authors":"Merlin Engelke, Christian Martin Brieske, Vicky Parmar, Nils Flaschel, Anisa Kureishi, Rene Hosch, Sven Koitka, Cynthia Sabrina Schmidt, Peter A Horn, Felix Nensa","doi":"10.1159/000528428","DOIUrl":"10.1159/000528428","url":null,"abstract":"<p><strong>Introduction: </strong>An increasing shortage of donor blood is expected, considering the demographic change in Germany. Due to the short shelf life and varying daily fluctuations in consumption, the storage of platelet concentrates (PCs) becomes challenging. This emphasizes the need for reliable prediction of needed PCs for the blood bank inventories. Therefore, the objective of this study was to evaluate multimodal data from multiple source systems within a hospital to predict the number of platelet transfusions in 3 days on a per-patient level.</p><p><strong>Methods: </strong>Data were collected from 25,190 (42% female and 58% male) patients between 2017 and 2021. For each patient, the number of received PCs, platelet count blood tests, drugs causing thrombocytopenia, acute platelet diseases, procedures, age, gender, and the period of a patient's hospital stay were collected. Two models were trained on samples using a sliding window of 7 days as input and a day 3 target. The model predicts whether a patient will be transfused 3 days in the future. The model was trained with an excessive hyperparameter search using patient-level repeated 5-fold cross-validation to optimize the average macro F2-score.</p><p><strong>Results: </strong>The trained models were tested on 5,022 unique patients. The best-performing model has a specificity of 0.99, a sensitivity of 0.37, an area under the precision-recall curve score of 0.45, an MCC score of 0.43, and an F1-score of 0.43. However, the model does not generalize well for cases when the need for a platelet transfusion is recognized.</p><p><strong>Conclusion: </strong>A patient AI-based platelet forecast could improve logistics management and reduce blood product waste. In this study, we build the first model to predict patient individual platelet demand. To the best of our knowledge, we are the first to introduce this approach. Our model predicts the need for platelet units for 3 days in the future. While sensitivity underperforms, specificity performs reliably. The model may be of clinical use as a pretest for potential patients needing a platelet transfusion within the next 3 days. As sensitivity needs to be improved, further studies should introduce deep learning and wider patient characterization to the methodological multimodal, multisource data approach. Furthermore, a hospital-wide consumption of PCs could be derived from individual predictions.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"277-285"},"PeriodicalIF":1.9,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/77/tmh-0050-0277.PMC10521242.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41148935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of Bone Marrow Necrosis following Severe Vaso-Occlusive Crisis in Patient with Compound Heterozygous Sickle Cell Disease.","authors":"Daniel N Marco,&nbsp;Joan Cid,&nbsp;Marta Garrote,&nbsp;Albert Cortés-Bullich,&nbsp;Ferran Seguí,&nbsp;Miquel Lozano","doi":"10.1159/000529500","DOIUrl":"https://doi.org/10.1159/000529500","url":null,"abstract":"<p><strong>Introduction: </strong>Bone marrow necrosis is a rare entity that can develop in context of a sickle cell disease vaso-occlusive crisis. Its physiopathology is related to an endothelial dysfunction taking place in bone marrow microvasculature.</p><p><strong>Case presentation: </strong>A 30-year-old patient with history of compound heterozygous sickle cell disease was admitted following SARS-CoV-2 infection with fever and diarrhea. After initial favorable evolution, he developed a severe vaso-occlusive crisis with intense hemolysis and multi-organ ischemic complications. Patient then developed high fever and hypoxemia. With the suspicion of acute thoracic syndrome, a red blood cell exchange was performed. Respiratory symptoms ceased but patient persisted febrile with very high levels of acute phase reactants, persistent pancytopenia, and leucoerythroblastic reaction. An infectious cause was ruled out. Afterward, bone marrow aspiration and bone marrow biopsy showed a picture of bone marrow necrosis, which is an extremely rare complication of vaso-occlusive crisis but, paradoxically, more frequent in milder heterozygote cases of sickle cell disease. Ultimately, large deposits of complement membrane attack complex (particles C5b-9) were demonstrated after incubation of laboratory endothelial cells with activated plasma from the patient.</p><p><strong>Discussion: </strong>The clinical presentation and findings are consistent with a case of bone marrow necrosis. In this setting, the demonstration of complement as a potential cause of the endothelial dysfunction mimics the pattern of atypical hemolytic uremic syndrome and other microangiopathic anemias. This dysregulation may be a potential therapeutic target for new complement activation blockers.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"360-364"},"PeriodicalIF":2.2,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/27/tmh-0050-0360.PMC10521221.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Different Hemoglobin Levels on Near-Infrared Spectroscopy-Derived Cerebral Oxygen Saturation in Elderly Patients Undergoing Noncardiac Surgery.","authors":"Achilles Delis,&nbsp;Derek Bautz,&nbsp;Heidi Ehrentraut,&nbsp;Karin Doll,&nbsp;Thomas M Randau,&nbsp;Andreas C Strauss,&nbsp;Ivana Habicht,&nbsp;Erdem Güresir,&nbsp;Holger Bogatsch,&nbsp;Peter Kranke,&nbsp;Maria Wittmann,&nbsp;Patrick Meybohm,&nbsp;Markus Velten","doi":"10.1159/000528888","DOIUrl":"https://doi.org/10.1159/000528888","url":null,"abstract":"<p><strong>Background: </strong>Near-infrared spectroscopy (NIRS) is a commonly used technique to evaluate tissue oxygenation and prevent harmful cerebral desaturation in the perioperative setting. The aims of the present study were to assess whether surgery-related anemia can be detected via NIRS of cerebral oxygen saturation and to investigate the effects of different perioperative transfusion strategies on cerebral oxygenation, potentially affecting transfusion decision-making.</p><p><strong>Study design and methods: </strong>Data from the ongoing multicenter LIBERAL-Trial (liberal transfusion strategy to prevent mortality and anemia-associated ischemic events in elderly noncardiac surgical patients, LIBERAL) were used. In this single-center sub-study, regional cerebral oxygenation saturation (rSO₂) was evaluated by NIRS at baseline, pre-, and post-RBC transfusion. The obtained values were correlated with blood gas analysis-measured Hb concentrations.</p><p><strong>Results: </strong>rSO₂ correlated with Hb decline during surgery (<i>r</i> = 0.35, <i>p</i> < 0.0001). Different RBC transfusion strategies impacted rSO₂ such that higher Hb values resulted in higher rSO₂. Cerebral desaturation occurred at lower Hb values more often.</p><p><strong>Discussion: </strong>Cerebral oxygenation monitoring using NIRS provides noninvasive rapid and continuous information regarding perioperative alterations in Hb concentration without the utilization of patients' blood for blood sampling. Further investigations are required to demonstrate if cerebral rSO₂ may be included in future individualized transfusion decision strategies.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"270-276"},"PeriodicalIF":2.2,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/4c/tmh-0050-0270.PMC10521215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41140565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Screening of Blood Donors for <i>Babesia</i> in Tyrol, Austria.","authors":"Evan M Bloch, Anita Siller, Laura Tonnetti, Steven J Drews, Bryan R Spencer, Doris Hedges, Tessa Mergenthal, Marijke Weber-Schehl, Manfred Astl, Eshan U Patel, Manfred Gaber, Harald Schennach","doi":"10.1159/000528793","DOIUrl":"10.1159/000528793","url":null,"abstract":"<p><strong>Introduction: </strong><i>Babesia</i> is a tick-borne intraerythrocytic parasite that is globally ubiquitous, yet understudied. Several species of <i>Babesia</i> have been shown to be transfusion-transmissible. <i>Babesia</i> has been reported in blood donors, animals, and ticks in the Tyrol (Western Austria), and regional cases of human babesiosis have been described. We sought to characterize the risk of <i>Babesia</i> to the local blood supply.</p><p><strong>Methods: </strong>Prospective molecular testing was performed on blood donors who presented to regional, mobile blood collection drives in the Tyrol, Austria (27 May to October 4, 2021). Testing was conducted using the cobas^® Babesia assay (Roche Molecular Systems, Inc.), a commercial PCR assay approved for blood donor screening that is capable of detecting the 4 primary species causing human babesiosis (i.e., <i>B. microti</i>, <i>B. divergens</i>, <i>B. duncani</i>, and <i>B. venatorum</i>). A confirmatory algorithm to manage initial PCR-reactive samples was developed, as were procedures for donor and product management.</p><p><strong>Results: </strong>A total of 7,972 donors were enrolled and screened; 4,311 (54.1%) were male, with a median age of 47 years (IQR = 34-55). No positive cases of <i>Babesia</i> were detected, corresponding with an overall prevalence of 0.00% (95% CI: 0.00%, 0.05%).</p><p><strong>Discussion: </strong>The findings suggest that the prevalence of <i>Babesia</i> is low in Austrian blood donors residing in the Tyrol, even during months of peak tick exposure. Although one cannot conclude the absence of <i>Babesia</i> in this population given the limited sample size, the findings suggest that the regional risk of transfusion-transmitted babesiosis is low.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"330-333"},"PeriodicalIF":2.2,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/87/d1/tmh-0050-0330.PMC10521223.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PharmaNews","authors":"","doi":"10.1159/000529216","DOIUrl":"https://doi.org/10.1159/000529216","url":null,"abstract":"«Mit dem Innovationsforum Schmerzmedizin der Deutschen Gesellschaft für Schmerzmedizin e.V. (DGS) geben wir insbesondere Allgemeinmedizinern, Internisten, Orthopäden, Neurologen, Anästhesisten und Schmerzmedizinern die Möglichkeit, ihr Fachwissen zu vertiefen und neue Impulse für ihre tägliche Arbeit zu erhalten», so DGS-Präsident Dr. Johannes Horlemann. Die Hämophilie ist ein neues Thema der jährlich stattfindenden Fortbildungsveranstaltung. «Schmerzen werden bei dieser seltenen Erkrankung unzureichend erfasst und behandelt. Darauf wollen wir aufmerksam machen», erklärte Horlemann. Bei der Hämophilie treten spontane innere Blutungen, meist in den Gelenken (80%) auf. Akute Schmerzen – verbunden mit Schwellungen und Bewegungseinschränkungen – sind die Folge. Wiederholte Blutungen können Entzündungsreaktionen, Knorpeldegenerationen und Gelenkdeformationen bedingen. Diese sogenannte hämophile Arthropathie kann wiederum zu chronischen Schmerzen führen. Mittels Prävention, Physiotherapie, Sport, Medikamenten, individueller Schmerztherapie oder auch mit einem chirurgischen Eingriff als letzte Option, lassen sich die Schmerzen wirksam behandeln. Durch eine prophylaktische Substitution von Gerinnungsfaktoren – angepasst an die Lebenssituation der Patient*innen – kann zudem das Auftreten der hämophilen Arthropathie deutlich verzögert und abgemildert werden. Horlemanns Appell: «Wir Schmerzmediziner sollten die Patient*innen niemals aufgeben, sondern uns intensiv um sie bemühen und intensiv mit Hämophiliebehandlern zusammenarbeiten.»","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 1","pages":"71 - 74"},"PeriodicalIF":2.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42519785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"","doi":"10.1159/000529509","DOIUrl":"https://doi.org/10.1159/000529509","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48005356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Invasive Zinc Protoporphyrin Screening Offers Opportunities for Secondary Prevention of Iron Deficiency in Blood Donors.","authors":"Anne Schliemann,&nbsp;Christian Homann,&nbsp;Georg Hennig,&nbsp;Alexander Lang,&nbsp;Lesca Miriam Holdt,&nbsp;Michael Vogeser,&nbsp;Ronald Sroka,&nbsp;Herbert Stepp,&nbsp;Franz Weinauer,&nbsp;Ernst-Markus Quenzel","doi":"10.1159/000528545","DOIUrl":"https://doi.org/10.1159/000528545","url":null,"abstract":"<p><strong>Background: </strong>Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable.</p><p><strong>Study design and methods: </strong>In addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors.</p><p><strong>Results: </strong>NI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 μmol ZnPP/mol heme and very high correlation (Spearman's Rho = 0.938). Using a cutoff of 65 μmol ZnPP/mol heme, NI-tubing measurements (<i>n</i> = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors.</p><p><strong>Conclusion: </strong>NI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"303-312"},"PeriodicalIF":2.2,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/6f/tmh-0050-0303.PMC10521216.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41161613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Lutheran Blood Groups and Genetic Variants within <i>KLF1</i> among Thai Blood Donors.","authors":"Kamphon Intharanut,&nbsp;Piyathida Khumsuk,&nbsp;Oytip Nathalang","doi":"10.1159/000528654","DOIUrl":"https://doi.org/10.1159/000528654","url":null,"abstract":"<p><strong>Background: </strong>Lu^a and Lu^b are inherited as codominant allelic characters resulting from a single nucleotide variant (SNV) of the basal cell adhesion molecule (<i>BCAM</i>) gene. Red cells of the dominantly inherited suppressor of the Lutheran antigens In(Lu) phenotypically appear as Lu(a-b-) by the haemagglutination test. In(Lu) resulted from heterozygosity for mutations within the erythroid-specific Krüppel-like factor 1 (<i>KLF1</i>) gene. This study aimed to determine the frequency of the Lu(a) and Lu(b) phenotypes and genotypes and genetic variants of the distinct In(Lu) among Thai blood donors.</p><p><strong>Material and methods: </strong>Samples from 334 Thai donors were phenotyped with anti-Lu^a and anti-Lu^b. These DNA samples and an additional 1,370 donor DNA samples with unknown Lu(a)/Lu(b) phenotypes were genotyped using an in-house PCR-SSP. In the case of the three Lu(a-b-) donors, the <i>BCAM</i> and <i>KLF1</i> genes were analysed by PCR and sequencing.</p><p><strong>Results: </strong>A total of 331 of the 334 donors were Lu(a-b+), while the other observed phenotype, appearing as Lu(a-b-), was found among three donors. Of those three Lu(a-b-) donors with the <i>LU</i>*<i>02</i>/<i>02</i> genotype, we identified <i>KLF1</i> variant alleles, consisting of two variants: c.[304T>C, 1001C>G] and c.[304T>C, 519_525dupCGGCGCC], leading to the In(Lu) phenotype, and one homozygous variant (c.304T>C) mutation. Also, only one Thai donor was genotyped as <i>LU</i>*<i>01</i>/<i>02</i>, confirmed by serology test and DNA sequencing.</p><p><strong>Conclusion: </strong>In this study, we identified <i>KLF1</i> variants to be included in Lutheran typing analysis in Thai populations. Therefore, the application of genotyping and phenotyping methods has simultaneously been in use to screen and confirm the rare Lu(a+) and In(Lu) phenotypes.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"313-320"},"PeriodicalIF":2.2,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/fd/tmh-0050-0313.PMC10521248.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41137757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Single Nucleotide Variants in Intron 1 of the ABO Gene as Diagnostic Markers for the A₁ Blood Group.","authors":"Peter Bugert,&nbsp;Gabi Rink,&nbsp;Harald Klüter","doi":"10.1159/000528683","DOIUrl":"https://doi.org/10.1159/000528683","url":null,"abstract":"<p><strong>Introduction: </strong>The molecular diagnosis of the A₁ blood group is based on the exclusion of <i>ABO</i> gene variants causing blood groups A₂, B, or O. A specific genetic marker for the A₁ blood group is still missing. Recently, long-read ABO sequencing revealed four sequence variations in intron 1 as promising markers for the <i>ABO</i>*<i>A1</i> allele. Here, we evaluated the diagnostic values of the 4 variants in blood donors with regular and weak A phenotypes and genotypes.</p><p><strong>Methods: </strong>ABO phenotype data (A, B, AB, or O) were taken from the blood donor files. The <i>ABO</i> genotypes (low resolution) were known from a previous study and included the variants c.261delG, c.802G>A, c.803G>C, and c.1061delC. <i>ABO</i> variant alleles (<i>ABO</i>*<i>AW.06,</i>*<i>AW.08,</i>*<i>AW.09,</i>*<i>AW.13</i>, *<i>AW.30</i>, and *<i>A3.02</i>) were identified in weak A donors by sequencing the <i>ABO</i> exons before. For genotyping of the <i>ABO</i> intron 1 variants rs532436, rs1554760445, rs507666, and rs2519093, we applied TaqMan assays with endpoint fluorescence detection according to a standard protocol. Genotypes of the variants were compared with the ABO phenotype and genotype. Evaluation of diagnostic performance included sensitivity, specificity, positive (PPV), and negative predictive value (NPV).</p><p><strong>Results: </strong>In 1,330 blood donors with regular ABO phenotypes and genotypes, the intron 1 variants were significantly associated with the proposed A₁ blood group. In 15 donors, we found discrepancies to the genotype of at least one of the 4 variants. For the diagnosis of the ABO*A1 allele, the variants showed 98.79-99.48% sensitivity, 99.66-99.81% specificity, 98.80-99.31% PPV, and 99.66-99.86% NPV. Regarding the A phenotype, the diagnostic values were 99.02-99.41% sensitivity, 99.63-99.76% specificity, 99.41-99.61% PPV, and 99.39-99.63% NPV. The *<i>A1</i> marker allele of all intron 1 variants was also associated with the *<i>AW.06</i>, *<i>AW.13</i>, and *<i>AW.30</i> variants. Samples with *<i>AW.08</i>, *<i>AW.09</i>, and *<i>A3.02</i> variants lacked this association.</p><p><strong>Conclusion: </strong>The <i>ABO</i> intron 1 variants revealed significant association with the <i>ABO</i>*<i>A1</i> allele and the A phenotype. However, the intron 1 genotype does not exclude variant alleles causing weak A phenotypes. With the introduction of reliable tag, single nucleotide variants for the A₁, A₂, B, and O blood groups and the genotyping instead of phenotyping of the ABO blood group are getting more feasible on a routine basis.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 4","pages":"263-269"},"PeriodicalIF":2.2,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/85/tmh-0050-0263.PMC10521232.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}