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Developments in the International Journal of Laboratory Hematology 国际实验室血液学杂志》的发展动态
IF 3 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-16 DOI: 10.1111/ijlh.14287
Ian Mackie, Giuseppe D'Onofrio
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引用次数: 0
Complement inhibition in paroxysmal nocturnal hemoglobinuria: From biology to therapy 阵发性夜间血红蛋白尿症中的补体抑制:从生物学到治疗
IF 3 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-15 DOI: 10.1111/ijlh.14281
Francesco Versino, Bruno Fattizzo

Complement inhibitors are the mainstay of paroxysmal nocturnal hemoglobinuria (PNH) treatment. The anti-C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life-long intravenous fortnightly drug. Additionally, suboptimal response may occur in up to 2/3 of patients with persistent anemia due to incomplete control of intravascular hemolysis, development of upstream C3-mediated extravascular hemolysis (EVH), or concomitant bone marrow failure. Ravulizumab, a longer half-life anti-C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti-C5 concentrations. More recently, several other anti-C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti-C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti-factor B) and danicopan (anti-factor D). These drugs efficiently target EVH and are able to improve anemia and transfusion need in suboptimal responders to anti-C5. The route and schedule of administration (twice weekly subcutaneously for pegcetacoplan and twice or thrice oral daily dosing for iptacopan and danicopan, respectively) are very convenient but pose novel issues regarding adherence. Additionally, both anti-C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review, we will recapitulate PNH physiopathology, clinical presentation, and diagnosis and describe available and developing drugs that will lead to a precision medicine approach for this rare though heterogenous disease.

补体抑制剂是治疗阵发性夜间血红蛋白尿症(PNH)的主要药物。抗 C5 单克隆抗体 eculizumab 是第一种改善 PNH 溶血、血栓风险和存活率的治疗药物,但其代价是每两周一次的终身静脉注射。此外,由于未完全控制血管内溶血、出现上游 C3 介导的血管外溶血(EVH)或同时出现骨髓衰竭,多达 2/3 的持续贫血患者可能会出现次优反应。Ravulizumab是由eculizumab发展而来的半衰期更长的抗C5药物,每8周给药一次,为患者提供了更多便利,并通过建立更稳定的抗C5浓度减少了药代动力学突破性溶血(BTH)。最近,其他几种抗 C5 复合物(crovalimab、pozelimab、tesidolumab、cemdisiran、zilucoplan 和 coversin)也在临床试验中。此外,还利用抗 C3 pegcetacoplan 以及替代途径抑制剂 iptacopan(抗因子 B)和 danicopan(抗因子 D)对补体级联的上游抑制进行了探索。这些药物能有效针对 EVH,并能改善抗 C5 反应不佳者的贫血和输血需求。这些药物的给药途径和时间安排(pegcetacoplan 每周两次皮下注射,iptacopan 和 danicopan 每天分别口服两次或三次)非常方便,但在依从性方面存在新的问题。此外,抗 C5 和上游抑制剂并不能解决因感染、创伤和手术等补体扩增条件而导致的药效学 BTH 事件这一尚未满足的需求。在这篇综述中,我们将重述 PNH 的生理病理、临床表现和诊断,并介绍现有的和正在开发的药物,这些药物将为这种罕见的异质性疾病带来精准医疗方法。
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引用次数: 0
Congenital sideroblastic anemia with vacuolated bone marrow precursors secondary to SLC25A38 mutation—A great mimicker of Pearson syndrome 继发于 SLC25A38 基因突变的伴有空泡化骨髓前体的先天性红细胞性贫血--皮尔逊综合征的绝佳模仿者
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-11 DOI: 10.1111/ijlh.14282
Amiya Ranjan Nayak, Pratyusha Gudapati, Ganesh Kumar Viswanathan, Jasmita Dass, Mukul Aggarwal
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引用次数: 0
FLT-3 mutation maybe an inferior predictor of daratumumab therapy in acute myeloid leukemia patients relapsed after allogeneic stem cell transplantation 同种异体干细胞移植后复发的急性髓性白血病患者中,FLT-3突变可能是达拉单抗治疗的一个较差预测指标
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-10 DOI: 10.1111/ijlh.14275
Song Xue, Wenqiu Huang, Yongping Zhang, Fuhong Liu, Qi Hao, Jiajun Hu, Lei Yuan, Jingbo Wang
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引用次数: 0
Construction and validation of key genes-related prognosis model in children with acute myeloid leukaemia 构建和验证急性髓性白血病儿童关键基因相关预后模型
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-10 DOI: 10.1111/ijlh.14272
Fan Huang, Chuan Ming, Yuqian Jiang, Chenli Li, Cheng Tan

Introduction

To identify the differentially expressed genes of acute myeloid leukaemia (AML) and construct and verify a survival prognosis model combined with patient survival information.

Methods

The TARGET database was searched to identify differentially expressed peripheral blood genes in children with AML and healthy children. A gene set functional analysis and pathway analysis were performed using gene ontology and the KEGG pathway. A prognostic model for children with AML was constructed using univariate Cox, LASSO Cox regression and multivariate Cox regression analyses. Time-dependent receiver operating characteristic (ROC) curves were adopted to assess the predictive capacity of the prognostic models.

Results

In total, 1640 differentially expressed genes were screened (1119 upregulated and 521 downregulated genes). The differentially expressed genes were mainly involved in nutrient metabolism and cytochrome P450 metabolism. Six key genes related to the prognosis of AML, FAM157A, GPR78, IRX5, RP4-800G7.1, RP11-179H18.5 and RP11-61N20.3, were identified. Kaplan–Meier curves indicated that 3-year and 5-year overall survival was significantly higher in the low-risk group than in the high-risk group. The area under the ROC curve was 0.722. At different stages of AML, FAM157A and RP4-800G7.1 exhibited significant differences in expression. The expression levels of FAM157A were significantly decreased in AML, whereas the expression levels of GPR78, IRX5, RP4-800G7.1, RP11-179H18.5 and RP11-61N20.3 were significantly increased in AML.

Conclusion

A prognosis-related gene model of AML was successfully constructed, and the expression levels of the model genes varied with AML stage.

方法检索TARGET数据库,确定急性髓性白血病(AML)患儿和健康儿童外周血中差异表达的基因。利用基因本体论和 KEGG 通路进行了基因组功能分析和通路分析。通过单变量 Cox、LASSO Cox 回归和多变量 Cox 回归分析,建立了急性髓细胞性白血病患儿的预后模型。结果共筛选出1640个差异表达基因(1119个上调基因和521个下调基因)。差异表达基因主要涉及营养代谢和细胞色素 P450 代谢。研究发现了六个与急性髓细胞性白血病预后相关的关键基因:FAM157A、GPR78、IRX5、RP4-800G7.1、RP11-179H18.5和RP11-61N20.3。Kaplan-Meier 曲线显示,低风险组的 3 年和 5 年总生存率明显高于高风险组。ROC 曲线下的面积为 0.722。在急性髓细胞性白血病的不同阶段,FAM157A和RP4-800G7.1的表达有显著差异。结论 成功构建了急性髓细胞性白血病预后相关基因模型,模型基因的表达水平随急性髓细胞性白血病分期而变化。
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引用次数: 0
Noncriteria antiphospholipid antibodies in antiphospholipid syndrome 抗磷脂综合征中的非标准抗磷脂抗体
IF 3 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-07 DOI: 10.1111/ijlh.14268
Katrien M. J. Devreese

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant, anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several noncriteria aPL have been identified. Some noncriteria aPL are well studied, such as IgA aCL and aβ2GPI, the antiphosphatidylserine-prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2-glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other noncriteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin-cardiolipin complex, anti-protein S/protein C. Measurement of some of these noncriteria aPL (aPS/PT, aDI) is useful in the laboratory work-out of APS in specific situations. We have to differentiate between patients who are positive for noncriteria aPL only, and patients who have both criteria and noncriteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on noncriteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified.

抗磷脂抗体(aPL)是一组异质性自身抗体,但只有狼疮抗凝物、抗心磷脂(aCL)和抗β2-糖蛋白 I 抗体(aβ2GPI)IgG 或 IgM 被列为实验室分类标准。血清阴性 APS 患者通常指具有 APS 临床症状但 aPL 检测阴性的患者。经典 aPL 标准的阴性并不排除其他 aPL 的存在。目前已发现几种非标准 aPL。一些非标准 aPL 已被充分研究,如 IgA aCL 和 aβ2GPI、抗磷脂酰丝氨酸-凝血酶原(aPS/PT)抗体和抗β2-糖蛋白 I 结构域 I 的抗体(aDI),后两类抗体因其在血栓事件和妊娠并发症中的作用而受到更多关注。其他已研究过的非标准 aPL 包括抗附件蛋白 V、凝血酶原、磷脂酰乙醇胺、磷脂酸、磷脂酰丝氨酸、磷脂酰肌醇、波形蛋白-心磷脂复合物、抗蛋白 S/ 蛋白 C 抗体。我们必须区分仅非标准 aPL 阳性的患者和同时具有标准和非标准 aPL 的患者,以便研究它们在 APS 诊断或风险分层中的作用。对非标准 aPL 的研究还在继续,因为这些抗体的临床意义尚未完全明确。
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引用次数: 0
A novel α0-thalassemia deletion in a Brazilian child with Hb H disease: −−Mococa 一名患有 Hb H 病的巴西儿童的新型 α0 地中海贫血缺失:--莫科卡
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-03 DOI: 10.1111/ijlh.14277
A. M. Soler, G. A. Pedroso, A. P. M. Geraldo, D. M. Albuquerque, F. F. Costa, M. N. N. Santos, J. Knijnenburg, C. L. Harteveld, M. F. Sonati, J. A. da Luz
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引用次数: 0
Ectopic band 3 expression as a cause of mature ovarian teratoma-associated secondary autoimmune hemolytic anemia 异位带 3 表达是成熟卵巢畸胎瘤相关继发性自身免疫性溶血性贫血的病因之一
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-02 DOI: 10.1111/ijlh.14276
Tomonori Ochiai, Hajime Yasuda, Hisaya Akiba, Karin Ashizawa, Erina Hosoya, Jun Ando, Sachiko Miyake, Miki Ando
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引用次数: 0
Laboratory assessment of antiphospholipid syndrome: Laboratory data 抗磷脂综合征的实验室评估:实验室数据
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-02 DOI: 10.1111/ijlh.14273
Camilla J. Kobylecki, Signe Vedel-Krogh, Shoaib Afzal, Jens P. Goetze

Introduction

Thorough assessment of the antiphospholipid syndrome (APS) includes retesting of positive antiphospholipid antibody (aPL) tests after at least 12 weeks, and a full antiphospholipid antibody profile. To what extent this work-up is done in clinical practice is unknown.

Methods

Data on 25 116 in- and out-hospital patients tested for the presence of lupus anticoagulant (LA), the aPL which most strongly correlates with thrombosis, was extracted from the laboratory information system of the only laboratory that performs LA tests in the Capital Region, Denmark. We estimated fraction of repeated tests, tests repeated within the recommended time span, and fraction with a full aPL profile.

Results

Out of 25 116 patients, 843 were positive for LA (3.3%), and 3948 results were inconclusive (16%). Only 51% (95% CI of the proportion: 48%–54%) (n = 431) of positive tests were repeated. The proportion of inconclusive LA test results increased from 13% (12%–15%) in 2009 to 20% (19%–22%) in 2020. Out of the positive tests repeated within the first year, only 60/353 (17%; 13%–21%) were repeated within 12–16 weeks; 177/353 (50%; 45%–55%) were re-tested within the first 12 weeks of first positive test result. The proportion of patients with a full antiphospholipid antibody profile increased from 161/1978 (8%) in 2010 to 1041/1978 (43%) in 2020.

Conclusion

We found several issues with the laboratory workup of APS. This indicates a need for increased awareness of comprehensive laboratory assessment of possible APS as well as a closer collaboration between the laboratory and clinicians.

简介:抗磷脂综合征(APS)的全面评估包括至少12周后对抗磷脂抗体(aPL)阳性患者进行复查,以及全面的抗磷脂抗体谱检查。但在临床实践中,这种检查在多大程度上得到了执行还不得而知:从丹麦首都地区唯一一家进行狼疮抗凝物检测的实验室的实验室信息系统中提取了25 116名院内外患者的数据,以检测是否存在狼疮抗凝物(LA),狼疮抗凝物是与血栓形成关系最密切的一种抗磷脂抗体。我们估算了重复检测的比例、在建议时间跨度内重复检测的比例以及具有完整 aPL 资料的比例:在 25 116 名患者中,843 人的 LA 检测结果呈阳性(3.3%),3948 人的检测结果不确定(16%)。只有 51%(比例的 95% CI:48%-54%)的阳性检测结果(n = 431)被重复检测。LA检测结果不确定的比例从2009年的13%(12%-15%)上升到2020年的20%(19%-22%)。在第一年内复检的阳性检测结果中,只有 60/353 例(17%;13%-21%)在 12-16 周内复检;177/353 例(50%;45%-55%)在首次检测结果呈阳性的前 12 周内复检。抗磷脂抗体全谱患者的比例从2010年的161/1978(8%)增加到2020年的1041/1978(43%):我们发现 APS 的实验室检查存在一些问题。结论:我们发现实验室对 APS 的检查存在一些问题,这表明有必要提高对可能的 APS 进行全面实验室评估的认识,并加强实验室与临床医生之间的合作。
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引用次数: 0
Reference intervals in extended new red blood cell parameters based on gestational age on the first day of newborns 基于新生儿出生第一天胎龄的扩展新红细胞参数参考区间。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-03-30 DOI: 10.1111/ijlh.14279
Aslıhan Çomruk, Zühre Kaya, Serap Kirkiz Kayalı, Ülker Koçak, Canan Türkyılmaz, Esin Koç
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引用次数: 0
期刊
International Journal of Laboratory Hematology
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