Henriette Røed-Undlien, Nina Haagenrud Schultz, Erik Koldberg Amundsen, Birgit M. Wollmann, Espen Molden, Rupali R. Akerkar, Johannes Lagethon Bjørnstad
Introduction
Hemolytic interference may impact various laboratory tests, including coagulation analyses. Apixaban is the most commonly used direct oral anticoagulant in Norway, and there is lacking knowledge on how apixaban concentration measurements might be influenced by hemolysis. Moreover, hemolysis-induced alterations in apixaban levels could potentially impact the risk of bleeding in specific clinical scenarios. We wanted to study whether hemolysis would increase apixaban concentration and investigate the impact of hemolytic interference on apixaban concentration measurements.
Methods
Blood samples from 20 apixaban-treated patients and 8 healthy controls were hemolyzed in vitro by a freeze method. The degree of hemolysis was measured with plasma free hemoglobin (PfHb) at baseline and two levels of hemolysis. Apixaban concentration was measured in plasma using both the chromogenic anti-Xa method and the ultraperformance liquid chromatography mass spectrometry (UPLC-MS). Thrombin generation assay was performed to assess coagulability.
Results
UPLC-MS measurements showed a mean concentration change of −1.66% (±3.2%, p = 0.005) and anti-Xa assay showed a mean concentration change of 3.37% (±6.5%, p = 0.09) with increasing hemolysis. Thrombin generation lagtime decreased, and endogenous thrombin potential and peak thrombin increased with increasing hemolysis in both the control group and the apixaban group.
Conclusion
Apixaban concentration measurements by anti-Xa assay and UPLC-MS were not affected by hemolysis to a clinically relevant extent. Furthermore, hemolysis did not lead to hypocoagulability when assessed by thrombin generation.
导言溶血干扰可能会影响各种实验室检测，包括凝血分析。阿哌沙班是挪威最常用的直接口服抗凝剂，目前还不清楚溶血会如何影响阿哌沙班的浓度测量。此外，溶血引起的阿哌沙班浓度变化可能会影响特定临床情况下的出血风险。我们希望研究溶血是否会增加阿哌沙班的浓度，并调查溶血干扰对阿哌沙班浓度测量的影响：方法：采用冷冻法对 20 名阿哌沙班治疗患者和 8 名健康对照者的血样进行体外溶血。用血浆游离血红蛋白（PfHb）测量基线和两个溶血水平的溶血程度。血浆中的阿哌沙班浓度采用显色抗 Xa 法和超高效液相色谱质谱法（UPLC-MS）进行测定。进行凝血酶生成测定以评估凝血能力：超高效液相色谱-质谱测定显示，随着溶血量的增加，平均浓度变化为-1.66%（±3.2%，p = 0.005），抗 Xa 检测显示平均浓度变化为 3.37%（±6.5%，p = 0.09）。对照组和阿哌沙班组随着溶血量的增加，凝血酶生成滞后时间减少，内源性凝血酶潜能和凝血酶峰值增加：通过抗 Xa 检测法和超高效液相色谱-质谱法测量的阿哌沙班浓度不会受到溶血的临床影响。此外，通过凝血酶生成评估溶血并不会导致低凝状态。
{"title":"Does in vitro hemolysis affect measurements of plasma apixaban concentration by UPLC-MS and anti-Xa assay?","authors":"Henriette Røed-Undlien, Nina Haagenrud Schultz, Erik Koldberg Amundsen, Birgit M. Wollmann, Espen Molden, Rupali R. Akerkar, Johannes Lagethon Bjørnstad","doi":"10.1111/ijlh.14311","DOIUrl":"10.1111/ijlh.14311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hemolytic interference may impact various laboratory tests, including coagulation analyses. Apixaban is the most commonly used direct oral anticoagulant in Norway, and there is lacking knowledge on how apixaban concentration measurements might be influenced by hemolysis. Moreover, hemolysis-induced alterations in apixaban levels could potentially impact the risk of bleeding in specific clinical scenarios. We wanted to study whether hemolysis would increase apixaban concentration and investigate the impact of hemolytic interference on apixaban concentration measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood samples from 20 apixaban-treated patients and 8 healthy controls were hemolyzed in vitro by a freeze method. The degree of hemolysis was measured with plasma free hemoglobin (PfHb) at baseline and two levels of hemolysis. Apixaban concentration was measured in plasma using both the chromogenic anti-Xa method and the ultraperformance liquid chromatography mass spectrometry (UPLC-MS). Thrombin generation assay was performed to assess coagulability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>UPLC-MS measurements showed a mean concentration change of −1.66% (±3.2%, <i>p</i> = 0.005) and anti-Xa assay showed a mean concentration change of 3.37% (±6.5%, <i>p</i> = 0.09) with increasing hemolysis. Thrombin generation lagtime decreased, and endogenous thrombin potential and peak thrombin increased with increasing hemolysis in both the control group and the apixaban group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Apixaban concentration measurements by anti-Xa assay and UPLC-MS were not affected by hemolysis to a clinically relevant extent. Furthermore, hemolysis did not lead to hypocoagulability when assessed by thrombin generation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 5","pages":"946-952"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163149","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}
Rebeca Jurado Tapiador, P. González, I. Hernandez-Rodriguez
Sitosterolemia is a rare autosomal recessive disease that lead to an increase in the intestinal absorption and decreased biliary excretion plant sterols. It is caused by mutations in ABCG5 and ABCG8 genes, encoring sterolin-1 and sterolin-2 protein. The main clinical manifestations are xanthomas, premature atherosclerosis, arthralgia and, of note, hematological alterations. As in many other systemic diseases, hematological manifestations may be the only notable finding, for this reason we want to highlight the importance of multidisciplinary work and raise awareness of this rare disease that can lead to serious consequences if not treated prematurely. Here we present a case of this disease as well as its entire diagnostic process developed from a simple analytical alteration.
{"title":"Late diagnosis of sitosterolemia in an adult case with unexplained hemolytic anemia","authors":"Rebeca Jurado Tapiador, P. González, I. Hernandez-Rodriguez","doi":"10.1111/ijlh.14322","DOIUrl":"10.1111/ijlh.14322","url":null,"abstract":"<p>Sitosterolemia is a rare autosomal recessive disease that lead to an increase in the intestinal absorption and decreased biliary excretion plant sterols. It is caused by mutations in <i>ABCG5</i> and <i>ABCG8</i> genes, encoring sterolin-1 and sterolin-2 protein. The main clinical manifestations are xanthomas, premature atherosclerosis, arthralgia and, of note, hematological alterations. As in many other systemic diseases, hematological manifestations may be the only notable finding, for this reason we want to highlight the importance of multidisciplinary work and raise awareness of this rare disease that can lead to serious consequences if not treated prematurely. Here we present a case of this disease as well as its entire diagnostic process developed from a simple analytical alteration.</p>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 6","pages":"985-987"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163150","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}
Sophie Melicine, Capucine Habay, Wiame Ghammad, Julie Carré, Jean Luc Diehl, David M. Smadja, Nicolas Gendron, Dominique Helley, Laetitia Mauge
Introduction
The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors.
Materials and Methods
This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method.
Results
Removal with DOAC-Remove was specific of DOAC (apixaban n = 42, rivaroxaban n = 41, UFH n = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0–11.0] for apixaban (n = 26) and 4.5 days [IQR 2.0–5.8] for rivaroxaban (n = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban.
Conclusions
Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.
{"title":"DOAC-Remove to counteract the interference of anti-Xa oral anticoagulants on the monitoring of heparin","authors":"Sophie Melicine, Capucine Habay, Wiame Ghammad, Julie Carré, Jean Luc Diehl, David M. Smadja, Nicolas Gendron, Dominique Helley, Laetitia Mauge","doi":"10.1111/ijlh.14321","DOIUrl":"10.1111/ijlh.14321","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Removal with DOAC-Remove was specific of DOAC (apixaban <i>n</i> = 42, rivaroxaban <i>n</i> = 41, UFH <i>n</i> = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0–11.0] for apixaban (<i>n</i> = 26) and 4.5 days [IQR 2.0–5.8] for rivaroxaban (<i>n</i> = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 5","pages":"953-962"},"PeriodicalIF":2.2,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159326","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}
Shi Tao, Qianlei Huang, Weilun Zhou, Jing Chen, Yuxuan Man, Lang Chen, Yu Chen
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, which caused many patients to lose their precious lives. FOXO3 was a suppressor in various cancers, however, the role and mechanism of FOXO3 in DLBCL remain unclear.
Methods
Bioinformatics analysis was used to offer information FOXO3 expression and its expression for prognosis of DLBCL patients. The abundance of genes and proteins was evaluated using RT-qPCR and western blot. Cell proliferation and apoptosis was detected by CCK-8 and flow cytometry. The interactions among FOXO3, miR-34b, and HSPG2 were predicted by TransmiR and Starbase and validated using dual luciferase reporter assay, ChIP assay, and RIP assay.
Results
Our findings revealed that FOXO3 expression was abnormally declined in DLBCL cells. FOXO3 upregulation restrained cell proliferation and promoted cell apoptosis of DLBCL cells, while miR-34b inhibitor eliminated these influences. Similarly, miR-34b mimic suppressed malignant behaviors of DLBCL cells, which were abolished by HSPG2 overexpression. Mechanically, FOXO3 induced miR-34b expression through interacting with miR-34b promoter and HSPG2 was a targeted gene of miR-34b.
Conclusion
FOXO3 attenuated the capability of cell proliferation and promoted cell apoptosis rate of DLBCL cells through affecting miR-34b/HSPG2 axis, therefore inhibiting DLBCL progression.
背景：弥漫大 B 细胞淋巴瘤（DLBCL弥漫大B细胞淋巴瘤（DLBCL）是最常见的淋巴瘤类型，它使许多患者失去了宝贵的生命。FOXO3是多种癌症的抑制因子，然而，FOXO3在DLBCL中的作用和机制仍不清楚：方法：利用生物信息学分析提供 FOXO3 的表达及其对 DLBCL 患者预后的影响。采用 RT-qPCR 和 Western 印迹技术评估了基因和蛋白质的丰度。CCK-8和流式细胞术检测了细胞的增殖和凋亡。TransmiR和Starbase预测了FOXO3、miR-34b和HSPG2之间的相互作用，并使用双荧光素酶报告实验、ChIP实验和RIP实验进行了验证：结果：我们的研究结果表明，FOXO3在DLBCL细胞中的表达异常下降。FOXO3的上调抑制了DLBCL细胞的增殖并促进了细胞凋亡，而miR-34b抑制剂则消除了这些影响。同样，miR-34b模拟物抑制了DLBCL细胞的恶性行为，而HSPG2的过表达则消除了这些行为。从机理上讲，FOXO3通过与miR-34b启动子相互作用诱导miR-34b的表达，而HSPG2是miR-34b的靶基因：结论：FOXO3通过影响miR-34b/HSPG2轴，减弱了DLBCL细胞的增殖能力，促进了细胞凋亡率，从而抑制了DLBCL的进展。
{"title":"FOXO3 suppresses lymphoma progression through promoting miR-34b/HSPG2 axis","authors":"Shi Tao, Qianlei Huang, Weilun Zhou, Jing Chen, Yuxuan Man, Lang Chen, Yu Chen","doi":"10.1111/ijlh.14310","DOIUrl":"10.1111/ijlh.14310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, which caused many patients to lose their precious lives. FOXO3 was a suppressor in various cancers, however, the role and mechanism of FOXO3 in DLBCL remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bioinformatics analysis was used to offer information FOXO3 expression and its expression for prognosis of DLBCL patients. The abundance of genes and proteins was evaluated using RT-qPCR and western blot. Cell proliferation and apoptosis was detected by CCK-8 and flow cytometry. The interactions among FOXO3, miR-34b, and HSPG2 were predicted by TransmiR and Starbase and validated using dual luciferase reporter assay, ChIP assay, and RIP assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that FOXO3 expression was abnormally declined in DLBCL cells. FOXO3 upregulation restrained cell proliferation and promoted cell apoptosis of DLBCL cells, while miR-34b inhibitor eliminated these influences. Similarly, miR-34b mimic suppressed malignant behaviors of DLBCL cells, which were abolished by HSPG2 overexpression. Mechanically, FOXO3 induced miR-34b expression through interacting with miR-34b promoter and HSPG2 was a targeted gene of miR-34b.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FOXO3 attenuated the capability of cell proliferation and promoted cell apoptosis rate of DLBCL cells through affecting miR-34b/HSPG2 axis, therefore inhibiting DLBCL progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 5","pages":"885-893"},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077421","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":"Issue Information Covers","authors":"","doi":"10.1111/ijlh.14309","DOIUrl":"https://doi.org/10.1111/ijlh.14309","url":null,"abstract":"","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 S1","pages":"1-2"},"PeriodicalIF":3.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069105","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":"International Society for Laboratory Hematology: Focus on Education, 2024","authors":"Ruth Padmore","doi":"10.1111/ijlh.14292","DOIUrl":"https://doi.org/10.1111/ijlh.14292","url":null,"abstract":"","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 S1","pages":"8"},"PeriodicalIF":3.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069151","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}
Roberta Russo, Achille Iolascon, Immacolata Andolfo, Roberta Marra, Barbara Eleni Rosato
Hereditary dyserythropoietic anemias, or congenital dyserythropoietic anemias (CDAs), are rare disorders disrupting normal erythroid lineage development, resulting in ineffective erythropoiesis and monolinear cytopenia. CDAs include three main types (I, II, III), transcription-factor-related forms, and syndromic forms. The widespread use of next-generation sequencing in the last decade has unveiled novel causative genes and unexpected genotype–phenotype correlations. The discovery of the genetic defects underlying the CDAs not only facilitates accurate diagnosis but also enhances understanding of CDA pathophysiology. Notable advancements include identifying a hepatic-specific role of the SEC23B loss-of-function in iron metabolism dysregulation in CDA II, deepening CDIN1 dysfunction during erythroid differentiation, and uncovering a recessive CDA III form associated with RACGAP1 variants. Current treatments primarily rely on supportive measures tailored to disease severity and clinical features. Comparative studies with pyruvate kinase deficiency have illuminated new therapeutic avenues by elucidating iron dyshomeostasis and dyserythropoiesis mechanisms. We herein discuss recent progress in diagnostic methodologies, novel gene discoveries, and enhanced comprehension of CDA pathogenesis and molecular genetics.
遗传性红细胞生成障碍性贫血或先天性红细胞生成障碍性贫血（CDA）是一种罕见的疾病，会破坏红细胞系的正常发育，导致红细胞生成障碍和单核细胞减少。CDA 包括三种主要类型（I、II、III）、转录因子相关类型和综合征类型。近十年来，新一代测序技术的广泛应用揭示了新的致病基因和意想不到的基因型表型相关性。发现 CDA 的基因缺陷不仅有助于准确诊断，还能加深对 CDA 病理生理学的理解。值得注意的进展包括确定了 SEC23B 功能缺失在 CDA II 铁代谢失调中的肝特异性作用，深化了 CDIN1 在红细胞分化过程中的功能障碍，并发现了与 RACGAP1 变异相关的隐性 CDA III 型。目前的治疗主要依赖于针对疾病严重程度和临床特征的支持性措施。与丙酮酸激酶缺乏症的比较研究通过阐明铁失衡和红细胞生成障碍的机制，为治疗提供了新的途径。我们在此讨论诊断方法的最新进展、新基因的发现以及对 CDA 发病机制和分子遗传学的进一步理解。
{"title":"Updates on clinical and laboratory aspects of hereditary dyserythropoietic anemias","authors":"Roberta Russo, Achille Iolascon, Immacolata Andolfo, Roberta Marra, Barbara Eleni Rosato","doi":"10.1111/ijlh.14307","DOIUrl":"10.1111/ijlh.14307","url":null,"abstract":"<p>Hereditary dyserythropoietic anemias, or congenital dyserythropoietic anemias (CDAs), are rare disorders disrupting normal erythroid lineage development, resulting in ineffective erythropoiesis and monolinear cytopenia. CDAs include three main types (I, II, III), transcription-factor-related forms, and syndromic forms. The widespread use of next-generation sequencing in the last decade has unveiled novel causative genes and unexpected genotype–phenotype correlations. The discovery of the genetic defects underlying the CDAs not only facilitates accurate diagnosis but also enhances understanding of CDA pathophysiology. Notable advancements include identifying a hepatic-specific role of the <i>SEC23B</i> loss-of-function in iron metabolism dysregulation in CDA II, deepening <i>CDIN1</i> dysfunction during erythroid differentiation, and uncovering a recessive CDA III form associated with <i>RACGAP1</i> variants. Current treatments primarily rely on supportive measures tailored to disease severity and clinical features. Comparative studies with pyruvate kinase deficiency have illuminated new therapeutic avenues by elucidating iron dyshomeostasis and dyserythropoiesis mechanisms. We herein discuss recent progress in diagnostic methodologies, novel gene discoveries, and enhanced comprehension of CDA pathogenesis and molecular genetics.</p>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 4","pages":"595-605"},"PeriodicalIF":2.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924177","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}
Extracorporeal membrane oxygenation (ECMO) is a type of circulatory life support for patients with severe lung failure. The use of ECMO has increased worldwide since the pandemic of H1N1 in 2009 and more recently SARS-CoV-2 in 2020 both of which caused severe respiratory failure. ECMO patients experience both increased risk of bleeding and thrombosis. This is due to the pathological insult that damages the lungs, the ECMO circuit, coagulopathy, inflammation and anticoagulation. ECMO presents unique demands on the coagulation laboratory both in tests required to manage the patients and result interpretation. This is a personal opinion of 20 years ECMO experience as a clinical scientist and a short current review of the literature. It will focus on the laboratory coagulation tests used to manage ECMO patients, including different anticoagulants used, testing frequency and interpretation of the results.
{"title":"Interpretation of coagulation laboratory tests for patients on ECMO","authors":"Simon Davidson","doi":"10.1111/ijlh.14308","DOIUrl":"10.1111/ijlh.14308","url":null,"abstract":"<p>Extracorporeal membrane oxygenation (ECMO) is a type of circulatory life support for patients with severe lung failure. The use of ECMO has increased worldwide since the pandemic of H1N1 in 2009 and more recently SARS-CoV-2 in 2020 both of which caused severe respiratory failure. ECMO patients experience both increased risk of bleeding and thrombosis. This is due to the pathological insult that damages the lungs, the ECMO circuit, coagulopathy, inflammation and anticoagulation. ECMO presents unique demands on the coagulation laboratory both in tests required to manage the patients and result interpretation. This is a personal opinion of 20 years ECMO experience as a clinical scientist and a short current review of the literature. It will focus on the laboratory coagulation tests used to manage ECMO patients, including different anticoagulants used, testing frequency and interpretation of the results.</p>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 4","pages":"606-612"},"PeriodicalIF":2.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924172","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}
Divine Senanu Ametefe, Suzi Seroja Sarnin, Darmawaty Mohd Ali, George Dzorgbenya Ametefe, Dah John, Abdulmalik Adozuka Aliu, Zadok Zoreno
Introduction
Acute lymphoblastic leukemia (ALL) presents a formidable challenge in hematological malignancies, necessitating swift and precise diagnostic techniques for effective intervention. The conventional manual microscopy of blood smears, although widely practiced, suffers from significant limitations including labor-intensity and susceptibility to human error, particularly in distinguishing the subtle differences between normal and leukemic cells.
Methods
To overcome these limitations, our research introduces the ALLDet classifier, an innovative tool employing deep transfer learning for the automated analysis and categorization of ALL from White Blood Cell (WBC) nuclei images. Our investigation encompassed the evaluation of nine state-of-the-art pre-trained convolutional neural network (CNN) models, namely VGG16, VGG19, ResNet50, ResNet101, DenseNet121, DenseNet201, Xception, MobileNet, and EfficientNetB3. We augmented this approach by incorporating a sophisticated contour-based segmentation technique, derived from the Chan-Vese model, aimed at the meticulous segmentation of blast cell nuclei in blood smear images, thereby enhancing the accuracy of our analysis.
Results
The empirical assessment of these methodologies underscored the superior performance of the EfficientNetB3 model, which demonstrated exceptional metrics: a recall specificity of 98.5%, precision of 95.86%, F1-score of 97.16%, and an overall accuracy rate of 97.13%. The Chan-Vese model's adaptability to the irregular shapes of blast cells and its noise-resistant segmentation capability were key to capturing the complex morphological changes essential for accurate segmentation.
Conclusion
The combined application of the ALLDet classifier, powered by EfficientNetB3, with our advanced segmentation approach, emerges as a formidable advancement in the early detection and accurate diagnosis of ALL. This breakthrough not only signifies a pivotal leap in leukemia diagnostic methodologies but also holds the promise of significantly elevating the standards of patient care through the provision of timely and precise diagnoses. The implications of this study extend beyond immediate clinical utility, paving the way for future research to further refine and enhance the capabilities of artificial intelligence in medical diagnostics.
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Tristan Klöter, Michael Metze, Ronny Kunze, Stephan Stöbe, Thomas Siegemund, Annelie Siegemund, Reinhard Henschler, Ulrich Laufs, Sirak Petros, Christian Pfrepper
Introduction
The activity of direct oral anticoagulants (DOAC) is important in acute clinical situations. Recent studies have suggested a strong influence of DOAC on the diluted Russel's Viper Venom Time (dRVVT). Therefore, it may be a suitable screening parameter for antithrombotic plasma activity of different DOAC. This prospective study aims to evaluate the sensitivity and specificity of dRVVT to detect residual DOAC activity at recommended plasma level thresholds.
Methods
A total of 80 patients were recruited, with 20 each treated with one of the four approved DOAC (apixaban, edoxaban, rivaroxaban or dabigatran), respectively. Blood plasma was collected before (baseline), at plasma peak time, and 6 and 12 h after DOAC. DRVVT was measured using the screen (LA1) and confirm (LA2) assay for lupus anticoagulant and compared with DOAC plasma levels. A reference range was calculated based on the dRVVT values of 61 healthy blood donors.
Results
All DOAC significantly prolonged the dRVVT especially at higher DOAC plasma levels. The LA1 time ≥41 s had a sensitivity ≥98% to detect edoxaban, dabigatran and rivaroxaban plasma levels ≥30 ng/mL but it was only 87% for apixaban. Sensitivity was ≥98% for all DOAC with the LA2 assay ≥36 s. The negative predictive value of a DOAC plasma level <30 ng/mL and dRVVT LA2 <36 s was 99%.
Conclusions
The dRVVT confirm assay (LA2) reliably detects residual DOAC plasma levels ≥30 ng/mL and could be useful to rapidly rule out relevant DOAC activity in emergency situations and to guide treatment decisions.
{"title":"Detection of direct oral anticoagulants with the diluted Russel's viper venom time","authors":"Tristan Klöter, Michael Metze, Ronny Kunze, Stephan Stöbe, Thomas Siegemund, Annelie Siegemund, Reinhard Henschler, Ulrich Laufs, Sirak Petros, Christian Pfrepper","doi":"10.1111/ijlh.14300","DOIUrl":"10.1111/ijlh.14300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The activity of direct oral anticoagulants (DOAC) is important in acute clinical situations. Recent studies have suggested a strong influence of DOAC on the diluted Russel's Viper Venom Time (dRVVT). Therefore, it may be a suitable screening parameter for antithrombotic plasma activity of different DOAC. This prospective study aims to evaluate the sensitivity and specificity of dRVVT to detect residual DOAC activity at recommended plasma level thresholds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 80 patients were recruited, with 20 each treated with one of the four approved DOAC (apixaban, edoxaban, rivaroxaban or dabigatran), respectively. Blood plasma was collected before (baseline), at plasma peak time, and 6 and 12 h after DOAC. DRVVT was measured using the screen (LA1) and confirm (LA2) assay for lupus anticoagulant and compared with DOAC plasma levels. A reference range was calculated based on the dRVVT values of 61 healthy blood donors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All DOAC significantly prolonged the dRVVT especially at higher DOAC plasma levels. The LA1 time ≥41 s had a sensitivity ≥98% to detect edoxaban, dabigatran and rivaroxaban plasma levels ≥30 ng/mL but it was only 87% for apixaban. Sensitivity was ≥98% for all DOAC with the LA2 assay ≥36 s. The negative predictive value of a DOAC plasma level <30 ng/mL and dRVVT LA2 <36 s was 99%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The dRVVT confirm assay (LA2) reliably detects residual DOAC plasma levels ≥30 ng/mL and could be useful to rapidly rule out relevant DOAC activity in emergency situations and to guide treatment decisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 5","pages":"927-935"},"PeriodicalIF":2.2,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893102","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}
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