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The Research of a Large-Scale Analysis Platform for MNS Blood Group Identification Based on Long-Read Sequencing 基于长线程测序的 MNS 血型鉴定大规模分析平台的研究
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-05-21 DOI: 10.1016/j.tmrv.2024.150836
Hua Xu, Xiaomin Su, Qinqin Zuo, Liangzi Zhang, Xiaoyue Chu
The objective of this study was to devise a novel approach for determining MNS blood group utilizing long-read sequencing (LRS) and to identify intricate genome variations associated with this blood group system. In this study, a total of 60 blood samples were collected from randomly selected Chinese Han blood donors. The amplification of the full-length sequences of GYPA exon 2-7 (11 kb) and GYPB exon 2-6 (7 kb) was conducted on the blood samples obtained from these 60 donors. Subsequently, the sequencing of these amplified sequences was performed using the PacBio platform. The obtained sequencing data were then compared with the reference sequence of the human genome (GRCh38) utilizing the pbmm2 software, resulting in the acquisition of the haploid sequences of GYPA and GYPB. The serological typing prediction was conducted using the International Society of Blood Transfusion (ISBT) database, while the analysis of SNVs sites was performed using deepvariant v1.2.0 software and reference sequence alignment. A total of 60 samples yielded unambiguous high-quality haplotypes, which can serve as a standardized reference sequence for molecular biology typing of MNSs in the Chinese population. In a total of 60 serological samples, the LRS method successfully identified the M, N, S, and s blood group antigens by analyzing specific genetic variations (c.59, c.71, c.72 for GYPA, and c.143 for GYPB), which aligned with the results obtained through conventional serological techniques. 4 Mur samples that had been previously validated through serology and molecular biology were successfully confirmed, and complete haploid sequences were obtained. Notably, one of the Mur samples exhibited a novel breakpoint, GYP (B1-136-B ψ 137-212-A213-229-B230-366), thereby representing a newly identified subtype. Single molecule sequencing, which eliminates the necessity for PCR amplification, effectively encompasses GC and high repeat regions, enhancing accuracy in quantifying mutations with low abundance or frequency. By employing LRS analysis of the core region of GYPA and GYPB, diverse genotypes of MNS can be precisely and reliably identified in a single assay. This approach presents a comprehensive, expeditious, and precise novel method for the categorization and investigation of MNS blood group system.
本研究旨在设计一种利用长读程测序(LRS)确定 MNS 血型的新方法,并确定与该血型系统相关的复杂基因组变异。本研究从随机抽取的中国汉族献血者中采集了 60 份血样。对这 60 名献血者的血样进行了 GYPA 第 2-7 号外显子(11 kb)和 GYPB 第 2-6 号外显子(7 kb)的全长序列扩增。随后,使用 PacBio 平台对这些扩增序列进行了测序。利用 pbmm2 软件将获得的测序数据与人类基因组参考序列(GRCh38)进行比较,从而获得了 GYPA 和 GYPB 的单倍体序列。血清学分型预测是利用国际输血协会(ISBT)数据库进行的,而 SNVs 位点分析则是利用 deepvariant v1.2.0 软件和参考序列比对进行的。共有 60 份样本获得了无歧义的高质量单倍型,可作为中国人群 MNS 分子生物学分型的标准化参考序列。在 60 份血清样本中,LRS 方法通过分析特定的基因变异(GYPA 的 c.59、c.71、c.72 和 GYPB 的 c.143),成功鉴定了 M、N、S 和 s 血型抗原,与传统血清学技术得出的结果一致。先前通过血清学和分子生物学验证的 4 个 Mur 样本得到了成功确认,并获得了完整的单倍体序列。值得注意的是,其中一个穆氏样本显示了一个新的断裂点,即 GYP(B1-136-B ψ 137-212-A213-229-B230-366),从而代表了一个新发现的亚型。单分子测序无需进行 PCR 扩增,可有效覆盖 GC 和高重复区域,提高了低丰度或低频率突变量化的准确性。通过对 GYPA 和 GYPB 的核心区域进行 LRS 分析,一次检测就能准确可靠地鉴定出 MNS 的不同基因型。这种方法为 MNS 血型系统的分类和研究提供了一种全面、快速和精确的新方法。
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引用次数: 0
Whole Blood Donor Iron Management Across Europe: Experiences and Challenges in Four Blood Establishments 欧洲全血献血者铁质管理:四家血站的经验与挑战。
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-18 DOI: 10.1016/j.tmrv.2024.150860
K. van den Hurk , M. Arvas , D.J. Roberts , J. Castrén , C. Erikstrup
Whole blood donors lose iron while donating and frequent blood donation is therefore known to induce a risk of iron deficiency and/or anemia. In this review we present, compare and discuss the pros and cons of 4 distinctive donor iron management strategies in England, Finland, the Netherlands, and Denmark. Donor iron management policies in the countries concerned are described for the year 2021, and data on donor and donation numbers, low hemoglobin (Hb) deferral rates and Hb levels are presented. In England Hb levels were only measured in donors failing a copper sulphate test, while in the other 3 countries Hb is measured at every donation. In Finland, donors considered at risk of iron deficiency receive iron supplements, while in the Netherlands, ferritin-guided donation intervals without iron supplementation are in place. In Denmark, iron supplementation is provided to donors with low ferritin levels. Low-Hb deferral rates and average Hb levels are quite similar across the included countries, with the exception of higher deferral rates in England. To conclude, despite significant diversity in donor iron management approaches, low Hb deferral rates and average Hb levels are similar among the included countries except for England, where higher deferral rates were observed that are likely attributed to the absence of iron supplementation or ferritin-guided deferral. Achieving an optimal, more tailored iron management strategy requires further research and a nuanced understanding of both donor demographics and physiological responses to optimize the effectiveness and safety of blood donation practices.
全血献血者在献血过程中会流失铁,因此,频繁献血有可能导致缺铁和/或贫血。在这篇综述中,我们介绍、比较并讨论了英国、芬兰、荷兰和丹麦四国不同的献血者铁管理策略的利弊。文中描述了相关国家 2021 年的捐献者铁管理政策,并提供了有关捐献者和捐献数量、低血红蛋白(Hb)延迟率和 Hb 水平的数据。在英格兰,只对未通过硫酸铜检测的捐献者进行血红蛋白水平检测,而在其他 3 个国家,每次捐献都要检测血红蛋白。在芬兰,被认为有缺铁风险的捐献者会得到铁质补充剂,而在荷兰,铁蛋白指导下的捐献间隔期不需要铁质补充剂。在丹麦,为铁蛋白水平低的捐献者提供铁补充剂。除了英格兰的推迟率较高外,其他国家的低血红蛋白推迟率和平均血红蛋白水平都非常相似。总之,尽管捐献者铁质管理方法存在很大差异,但除英国外,其他国家的低血红蛋白推迟率和平均血红蛋白水平都很相似,英国的推迟率较高可能是由于没有进行铁质补充或在铁蛋白指导下进行推迟。要达到最佳的、更有针对性的铁管理策略,需要进一步的研究和对献血者人口统计学和生理反应的细致了解,以优化献血实践的有效性和安全性。
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引用次数: 0
Beta-Amyloid Related Neurodegenerative and Neurovascular Diseases: Potential Implications for Transfusion Medicine 与β-淀粉样蛋白相关的神经退行性疾病和神经血管疾病:输血医学的潜在影响
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-18 DOI: 10.1016/j.tmrv.2024.150858
Ryan T. Muir , Jeannie L. Callum , Amy Y.X. Yu , Moira K. Kapral , Richard H. Swartz , Sandra E. Black , Bradley J. MacIntosh , Dean A. Fergusson , Steven Kleinman , Andrew D. Demchuk , Peter K. Stys , Eric E. Smith , Michael D. Hill
Cerebral amyloid angiopathy (CAA) is a progressive cerebrovascular and neurodegenerative disorder that is caused by the aberrant accumulation of soluble beta-amyloid isoforms in the small vessel walls of the cerebral and cerebellar cortices and the leptomeninges. Vascular beta-amyloid deposition increases vulnerability to intracerebral hemorrhage (ICH). Clinically, CAA can be the underlying cause of up to half of spontaneous lobar ICHs and can also present with convexity subarachnoid hemorrhage, transient focal neurologic episodes and progressive cognitive decline leading to dementia. The majority of CAA is sporadic, with increasing prevalence with age and often coexists with Alzheimer's Disease (AD). Genetic and iatrogenic etiologies are rare. Cases of CAA and AD have been linked to the use of cadaveric pituitary hormone and later life iatrogenic CAA has also been described following early-life neurosurgical procedures with cadaveric dura grafts. Together these data suggest a capacity of beta-amyloid transmissibility. A recent study found that in over 1 million transfusion recipients from donors who later developed (i) >1 ICH or (ii) one ICH event and dementia, had an elevated risk of developing future ICH. Considering prior reports of transfusion associated variant-Creutzfeldt Jakob Disease in humans and in vivo evidence in sheep, coupled with emerging data supporting beta-amyloid's prion-like properties, raises the question of whether CAA could be transmissible by blood transfusion. This would also have implications for screening, especially in an era of emerging plasma biomarkers of cerebral amyloidosis. Given the public health concerns raised by this biologically plausible question, there is a need for future studies with well-characterized definitions – and temporal ascertainment – of CAA exposure and outcomes to examine whether CAA is transfusion-transmissible, and, if so, with what frequency and timing of onset.
脑淀粉样蛋白血管病变(CAA)是一种进行性脑血管和神经退行性疾病,由可溶性β-淀粉样蛋白异构体在大脑和小脑皮质以及脑膜的小血管壁上异常积聚引起。血管中的β-淀粉样蛋白沉积增加了脑内出血(ICH)的易感性。在临床上,高达一半的自发性脑叶 ICH 都是由 CAA 引起的,CAA 还可表现为凸面性蛛网膜下腔出血、一过性局灶性神经系统发作和进行性认知功能下降导致痴呆。大多数 CAA 是散发性的,发病率随着年龄的增长而增加,并经常与阿尔茨海默病(AD)并存。遗传和先天性病因很少见。CAA 和 AD 病例与使用尸体垂体激素有关,也有早年使用尸体硬脑膜移植物进行神经外科手术后出现晚年先天性 CAA 的病例。这些数据共同表明,β-淀粉样蛋白具有传递能力。最近的一项研究发现,在 100 多万名输血受者中,如果捐献者后来发生(i) 1 次 ICH 或 (ii) 1 次 ICH 事件和痴呆,那么他们将来发生 ICH 的风险就会升高。考虑到之前关于输血相关的人类变异型克雷兹费尔特-雅各布病的报道和绵羊的体内证据,再加上新出现的支持β-淀粉样蛋白的朊病毒样特性的数据,提出了 CAA 是否会通过输血传播的问题。这也将对筛查产生影响,尤其是在脑淀粉样变性血浆生物标志物不断涌现的时代。考虑到这一生物学上可信的问题所引发的公共卫生问题,今后需要对 CAA 的暴露和结果进行定义明确、时间确定的研究,以检查 CAA 是否可通过输血传播,如果是,发病的频率和时间如何。
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引用次数: 0
Universal irradiation of platelets: Does irradiation affect the quality, effectiveness, and safety of platelets for transfusion? 血小板的普遍辐照:辐照是否会影响输注血小板的质量、有效性和安全性?
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-07-04 DOI: 10.1016/j.tmrv.2024.150840
Lorna Cain , Louise J. Geneen , Michael Wiltshire , Catherine Kimber , Sue Proffitt , Josie Sandercock , Carolyn Dorée , Susan J. Brunskill , Lise J. Estcourt
We aimed to identify any detrimental effects on platelet quality and clinical effectiveness, of irradiated platelets compared to non-irradiated platelets for transfusion. The review was conducted in accordance with PRISMA guidelines. The protocol was prospectively registered on PROSPERO [CRD42023441930]. Our search identified 3002 references, of which we included 44 studies. Forty-one were in vitro only studies, two studies were in healthy volunteers, and one study reported clinical outcomes in thrombocytopenic patients. X-ray was used exclusively in three studies, and alongside gamma irradiation in one study. Two studies did not report the source of irradiation. The remaining 38 studies used gamma irradiation only. We assessed risk of bias (ROB) for studies reporting clinical and in vivo outcomes using ROB 2.0 (3 studies). We adapted a ROB tool designed for animal studies to assess ROB for the studies reporting in vitro outcomes (43 studies). We assessed the certainty of the evidence for the eight outcomes deemed most important to assess platelet quality and clinical effectiveness (where day 0 is the day of the blood draw).
  • High certainty of a small decrease in pH (day 7) with irradiation: mean difference (MD) 0.04 lower (95% CI, −0.07 to −0.00).
  • Moderate certainty of an increase in P-selectin (day 5) with irradiation: MD 1.58 % higher (95% CI, 0.72-2.45).
  • Moderate certainty of no difference in supernatant glucose (days 5 and 7) and P-selectin (day 7).
  • Very low certainty of any difference in pH (day 5), post-transfusion bleeding risk (WHO 2+), and post-transfusion platelet survival time.
Overall, gamma irradiation has little to no effect on most markers of platelet quality and effectiveness. Where there is evidence of detriment from irradiation, differences are small in vitro, and are unlikely to affect clinical outcomes following transfusion. However, the evidence base is limited. Only half the studies could be included in any analysis. There is very limited evidence for x-ray as a source of irradiation and, given the potential benefits of using x-ray over gamma irradiation (ease of use and safety requirements), we would welcome further research comparing x-ray to gamma, and x-ray to a non-irradiated control.
我们旨在确定,与用于输血的未经过辐照的血小板相比,经过辐照的血小板对血小板质量和临床效果是否有任何不利影响。审查按照 PRISMA 指南进行。研究方案在 PROSPERO [CRD42023441930] 上进行了前瞻性注册。我们在检索中发现了 3002 篇参考文献,其中包括 44 项研究。其中 41 项仅为体外研究,2 项为健康志愿者研究,1 项研究报告了血小板减少患者的临床结果。三项研究只使用了 X 射线,一项研究同时使用了伽马射线照射。两项研究没有报告照射源。其余 38 项研究仅使用伽马射线照射。我们使用 ROB 2.0 评估了报告临床和体内结果的研究的偏倚风险(ROB)(3 项研究)。我们调整了专为动物研究设计的 ROB 工具,以评估报告体外结果的研究(43 项研究)的偏倚风险。我们对评估血小板质量和临床疗效最重要的八项结果(第 0 天为抽血当天)的证据确定性进行了评估。总体而言,伽马辐照对大多数血小板质量和有效性指标几乎没有影响。如果有证据表明辐照会对血小板质量和有效性产生不利影响,那么这种影响在体外是微小的,不太可能影响输血后的临床结果。然而,证据基础是有限的。只有一半的研究可纳入任何分析。X 射线作为辐照源的证据非常有限,考虑到 X 射线辐照比伽马射线辐照的潜在优势(使用方便和安全要求),我们欢迎进一步研究 X 射线与伽马射线辐照的比较,以及 X 射线与非辐照对照的比较。
{"title":"Universal irradiation of platelets: Does irradiation affect the quality, effectiveness, and safety of platelets for transfusion?","authors":"Lorna Cain ,&nbsp;Louise J. Geneen ,&nbsp;Michael Wiltshire ,&nbsp;Catherine Kimber ,&nbsp;Sue Proffitt ,&nbsp;Josie Sandercock ,&nbsp;Carolyn Dorée ,&nbsp;Susan J. Brunskill ,&nbsp;Lise J. Estcourt","doi":"10.1016/j.tmrv.2024.150840","DOIUrl":"10.1016/j.tmrv.2024.150840","url":null,"abstract":"<div><div>We aimed to identify any detrimental effects on platelet quality and clinical effectiveness, of irradiated platelets compared to non-irradiated platelets for transfusion. The review was conducted in accordance with PRISMA guidelines. The protocol was prospectively registered on PROSPERO [CRD42023441930]. Our search identified 3002 references, of which we included 44 studies. Forty-one were <em>in vitro</em> only studies, two studies were in healthy volunteers, and one study reported clinical outcomes in thrombocytopenic patients. X-ray was used exclusively in three studies, and alongside gamma irradiation in one study. Two studies did not report the source of irradiation. The remaining 38 studies used gamma irradiation only. We assessed risk of bias (ROB) for studies reporting clinical and <em>in vivo</em> outcomes using ROB 2.0 (3 studies). We adapted a ROB tool designed for animal studies to assess ROB for the studies reporting <em>in vitro</em> outcomes (43 studies). We assessed the certainty of the evidence for the eight outcomes deemed most important to assess platelet quality and clinical effectiveness (where day 0 is the day of the blood draw).<ul><li><span>•</span><span><div>High certainty of a small decrease in pH (day 7) with irradiation: mean difference (MD) 0.04 lower (95% CI, −0.07 to −0.00).</div></span></li><li><span>•</span><span><div>Moderate certainty of an increase in P-selectin (day 5) with irradiation: MD 1.58 % higher (95% CI, 0.72-2.45).</div></span></li><li><span>•</span><span><div>Moderate certainty of no difference in supernatant glucose (days 5 and 7) and P-selectin (day 7).</div></span></li><li><span>•</span><span><div>Very low certainty of any difference in pH (day 5), post-transfusion bleeding risk (WHO 2+), and post-transfusion platelet survival time.</div></span></li></ul></div><div>Overall, gamma irradiation has little to no effect on most markers of platelet quality and effectiveness. Where there is evidence of detriment from irradiation, differences are small <em>in vitro</em>, and are unlikely to affect clinical outcomes following transfusion. However, the evidence base is limited. Only half the studies could be included in any analysis. There is very limited evidence for x-ray as a source of irradiation and, given the potential benefits of using x-ray over gamma irradiation (ease of use and safety requirements), we would welcome further research comparing x-ray to gamma, and x-ray to a non-irradiated control.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"38 4","pages":"Article 150840"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Expression Alterations of Blood Group Genes During Plasmodium Falciparum Infection in Orthochromatic Erythroblasts 正色红细胞感染恶性疟原虫期间血型基因的表达变化
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI: 10.1016/j.tmrv.2024.150837
Fang-Fang Liu , Ke Li
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引用次数: 0
Balancing Donor Health and Plasma Collection: A Systematic Review of the Impact of Plasmapheresis Frequency 平衡捐献者健康与血浆采集:血浆置换频率影响的系统回顾。
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-21 DOI: 10.1016/j.tmrv.2024.150851
Tine D'aes , Katja van den Hurk , Natalie Schroyens , Susan Mikkelsen , Pieter Severijns , Emmy De Buck , Peter O'Leary , Pierre Tiberghien , Veerle Compernolle , Christian Erikstrup , Hans Van Remoortel
Most plasma used for manufacturing plasma-derived medicinal products (PDMPs) such as albumin, immunoglobulin (Ig), and clotting factors is obtained from source plasma collected via plasmapheresis, the majority of which is contributed by the United States (US). While the demand for PDMPs continues to rise, it remains unclear whether high-frequency plasmapheresis, such as the twice-weekly plasma donation allowed in the US, may have any (long-term) adverse health effects on the donor. To investigate the frequency at which plasma can be donated without harm to the donor, the current systematic review explores the impact of plasma donation frequency on cardiovascular health, protein depletion, and adverse events in healthy plasma donors. We asked the following research question: What is the impact of plasmapheresis frequency (Intervention) on the safety or health (Outcome) of healthy donors (Population)? Six databases (PubMed, Embase, Web of Science, CINAHL, the Cochrane Library, and Transfusion Evidence Library), 2 clinical trial registries (ICTRP and clinicaltrials.gov), and the PROSPERO database were searched. Four observational and 2 experimental studies were included. The results showed that very high-frequency donation (twice per week) may result in a clinically relevant decrease in ferritin and bring IgG levels below the lower threshold of 6 g/l. However, the evidence is of low to very low certainty, and solid conclusions are hindered by the healthy donor effect and methodological limitations of the included studies. To determine a safe threshold donation frequency that minimizes any possible harmful effect on the donor, more high-quality prospective cohort studies and experimental studies are needed. We should expedite such studies to support recommendations, as conclusive evidence confirming or refuting the safety of maximum allowed donation frequencies is lacking. Donor protection is essential, given that healthy donors receive no direct medical benefit from donating plasma.
用于生产白蛋白、免疫球蛋白 (Ig) 和凝血因子等血浆衍生医药产品 (PDMP) 的血浆大多来自通过血浆置换术收集的源血浆,其中大部分来自美国。虽然对 PDMP 的需求持续上升,但高频率的血浆置换(如美国允许的每周两次血浆捐献)是否会对捐献者的健康产生任何(长期)不利影响仍不清楚。为了研究捐献血浆不会对捐献者造成伤害的频率,本系统综述探讨了血浆捐献频率对健康血浆捐献者的心血管健康、蛋白质消耗和不良事件的影响。我们提出了以下研究问题:血浆捐献频率(干预)对健康捐献者(人群)的安全或健康(结果)有什么影响?我们检索了六个数据库(PubMed、Embase、Web of Science、CINAHL、Cochrane Library 和 Transfusion Evidence Library)、两个临床试验登记处(ICTRP 和 clinicaltrials.gov)以及 PROSPERO 数据库。其中包括 4 项观察性研究和 2 项实验性研究。结果显示,非常高频率的捐献(每周两次)可能会导致铁蛋白的临床相关性下降,并使 IgG 水平低于 6 克/升的较低阈值。然而,这些证据的确定性较低或很低,而且由于健康捐献者效应和所纳入研究的方法局限性,无法得出可靠的结论。为了确定一个安全的捐献频率阈值,最大限度地减少可能对捐献者造成的有害影响,需要进行更多高质量的前瞻性队列研究和实验研究。我们应加快此类研究,以支持相关建议,因为目前尚缺乏确凿证据证实或反驳最高允许捐献频率的安全性。鉴于健康的捐献者不会从捐献血浆中获得直接的医疗益处,对捐献者的保护至关重要。
{"title":"Balancing Donor Health and Plasma Collection: A Systematic Review of the Impact of Plasmapheresis Frequency","authors":"Tine D'aes ,&nbsp;Katja van den Hurk ,&nbsp;Natalie Schroyens ,&nbsp;Susan Mikkelsen ,&nbsp;Pieter Severijns ,&nbsp;Emmy De Buck ,&nbsp;Peter O'Leary ,&nbsp;Pierre Tiberghien ,&nbsp;Veerle Compernolle ,&nbsp;Christian Erikstrup ,&nbsp;Hans Van Remoortel","doi":"10.1016/j.tmrv.2024.150851","DOIUrl":"10.1016/j.tmrv.2024.150851","url":null,"abstract":"<div><div>Most plasma used for manufacturing plasma-derived medicinal products (PDMPs) such as albumin, immunoglobulin (Ig), and clotting factors is obtained from source plasma collected via plasmapheresis, the majority of which is contributed by the United States (US). While the demand for PDMPs continues to rise, it remains unclear whether high-frequency plasmapheresis, such as the twice-weekly plasma donation allowed in the US, may have any (long-term) adverse health effects on the donor. To investigate the frequency at which plasma can be donated without harm to the donor, the current systematic review explores the impact of plasma donation frequency on cardiovascular health, protein depletion, and adverse events in healthy plasma donors. We asked the following research question: What is the impact of plasmapheresis frequency (Intervention) on the safety or health (Outcome) of healthy donors (Population)? Six databases (PubMed, Embase, Web of Science, CINAHL, the Cochrane Library, and Transfusion Evidence Library), 2 clinical trial registries (ICTRP and clinicaltrials.gov), and the PROSPERO database were searched. Four observational and 2 experimental studies were included. The results showed that very high-frequency donation (twice per week) may result in a clinically relevant decrease in ferritin and bring IgG levels below the lower threshold of 6 g/l. However, the evidence is of low to very low certainty, and solid conclusions are hindered by the <em>healthy donor effect</em> and methodological limitations of the included studies. To determine a safe threshold donation frequency that minimizes any possible harmful effect on the donor, more high-quality prospective cohort studies and experimental studies are needed. We should expedite such studies to support recommendations, as conclusive evidence confirming or refuting the safety of maximum allowed donation frequencies is lacking. Donor protection is essential, given that healthy donors receive no direct medical benefit from donating plasma.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"38 4","pages":"Article 150851"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultra-Massive Transfusion: Predictors of Occurrence and In-Hospital mortality From the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR) 超大量输血:澳大利亚和新西兰大量输血登记处(ANZ-MTR)的发生率和住院死亡率预测。
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-18 DOI: 10.1016/j.tmrv.2024.150857
Marsali Maclean , Cameron Wellard , Elham Ashrafi , Helen E. Haysom , Rosemary L. Sparrow , Erica M. Wood , Zoe K. McQuilten
Few data exist on patient clinical characteristics, predictors of occurrence and short- and long-term outcomes of ultra-massive transfusion (UMT), defined as receiving 20 units or more of red blood cells (RBCs) within 48h. This study analyses UMT events from the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR). The ANZ-MTR captured all patients at 29 participating sites receiving a massive transfusion (MT), defined as ≥5 units of RBCs within 4h. Of 9028 patients, 803 (8.9%) received an UMT. UMT patients were younger than other MT patients (median age 57y vs 62y; P < .001). In UMT and MT, males predominated (66.3% and 62.9%, respectively); and context was predominantly trauma (28.8% and 23%) and cardiothoracic surgery (CTS) (21.7% and 20.3%). Median RBC units received within 4h were 16 (UMT) and 6 (MT). In UMT, 4h FFP:RBC ratio (0.6 vs 0.4, P < .001), and 4h cryoprecipitate use (72.9% vs 39.9%, P < .001) were higher. Independent predictors of UMT (Odds Ratio; 95% CI) were age <60y (1.52; 1.28-1.79), baseline Hb >100g/L (1.31; 1.08-1.59), INR >1.5 (1.56; 1.24-1.96), and APTT >60s (4.49; 3.40-5.61). Predictors of in-hospital mortality in UMT included Charlson Comorbidity Index score ≥3 (11.20, 0.60 - 25.00) and bleeding context, with mortality less likely in liver transplant (0.07, 0.01-0.41) and more likely in vascular surgery (8.27, 1.54-72.85), compared with CTS. In-hospital mortality was higher in the UMT group compared with MT group (20.5% vs 44.2%, P < .001), however 5y survival following discharge was not significantly different between the groups (HR=0.87 [95%CI 0.64-1.18], P = .38). UMT patients are more commonly younger, with baseline coagulopathy, and have higher in-hospital mortality compared with MT. However, UMT is not futile: 55.8% survived to discharge, without significant difference in survival postdischarge between the groups.
超大量输血(UMT)是指在 48 小时内接受 20 个单位或更多的红细胞(RBC),有关超大量输血的患者临床特征、发生预测因素以及短期和长期结果的数据很少。本研究分析了澳大利亚和新西兰大量输血登记处(ANZ-MTR)的超大量输血事件。ANZ-MTR收集了29个参与地点所有接受大量输血(MT)的患者,大量输血的定义是在4小时内输注≥5个单位的红细胞。在 9028 名患者中,有 803 人(8.9%)接受了 UMT。UMT患者比其他MT患者更年轻(中位年龄为57岁 vs 62岁;P < .001)。在 UMT 和 MT 患者中,男性占多数(分别为 66.3% 和 62.9%);背景主要是创伤(分别为 28.8% 和 23%)和心胸外科(CTS)(分别为 21.7% 和 20.3%)。4 小时内收到的 RBC 单位中位数分别为 16 个(UMT)和 6 个(MT)。在 UMT 中,4 小时内 FFP:RBC 比率(0.6 vs 0.4,P < .001)和 4 小时内低温沉淀物使用率(72.9% vs 39.9%,P < .001)均较高。UMT 的独立预测因素(Odds Ratio; 95% CI)为年龄 100g/L (1.31;1.08-1.59)、INR >1.5 (1.56;1.24-1.96) 和 APTT >60s (4.49;3.40-5.61)。UMT 的院内死亡率预测因素包括 Charlson 生病指数评分≥3(11.20,0.60 - 25.00)和出血情况,与 CTS 相比,肝移植的死亡率较低(0.07,0.01-0.41),血管外科的死亡率较高(8.27,1.54-72.85)。与 MT 组相比,UMT 组的院内死亡率更高(20.5% vs 44.2%,P < .001),但出院后 5 年的存活率在两组间无显著差异(HR=0.87 [95%CI 0.64-1.18],P = .38)。与 MT 相比,UMT 患者通常更年轻,有基线凝血病,院内死亡率更高。然而,UMT 并非徒劳无益:55.8% 的患者存活至出院,两组患者出院后的存活率无明显差异。
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引用次数: 0
Isohemagglutinin titres: A comparison of pathogen reduced pooled platelets manufactured with platelet additive solution versus untreated pooled platelets 异血凝素滴度:使用血小板添加剂溶液制造的病原体减少型集合血小板与未经处理的集合血小板的比较
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-11-27 DOI: 10.1016/j.tmrv.2024.150853
Melanie Bodnar, Dora Lopes-Carvalho, Tammy Ison, Behr Ehsani-Moghaddam, Cindy Lever, Ilona Resz, Mei Yiep, Shuoyan Ning, Michelle Zeller, Charles Musuka

Introduction

Limitations in platelet inventory necessitate the use of ABO-incompatible (ABOi) platelets for transfusion with possible risk of an acute hemolytic transfusion reaction due to the presence of high titre (HT) isohemagglutinins (ISO). Pooled platelets psoralen-treated (PPPT) are manufactured following the division of 7 donor buffy coats in a platelet additive solution (PAS). The PAS:plasma ratio of 60:40 provides a dilutional effect on ISO levels. The purpose of this study is to compare the proportion of PPPT that test ISO HT positive versus untreated 4 donor platelet pools without PAS (UPP).

Methods

Component-based ISO titration was performed on 1001 UPP (November 8 2022-February 8 2023) and 1019 PPPT (June 1 2023-August 31 2023) followed by testing of 834 additional group O PPPT (September 1 2023-January 19 2024) to refine the HT rate estimate. All testing was performed at a single laboratory by a manual immediate spin tube method using an aliquot of platelet supernatant diluted 1:50 with saline tested separately against A1 and B cells. Agglutination with either/both A1 and B cell(s) constituted a positive HT result. The proportion of components with HT results were compared for PPPT vs UPP. Statistical analysis was performed using SAS with P-values calculated using the chi-square method.

Results

Of 1019 PPPT in PAS, 3 (0.29%) tested HT positive and all were group O. By comparison, 64/1001 (6.4%) UPP were HT positive (P-value <.0001). The rate of HT positivity by ABO blood group for PPPT vs UPP: Group O 3/559 (0.54%) vs 53/496 (10.6%) (P-value <.0001); Group A 0/439 (0%) vs 9/468 (1.9%); Group B 0/21 (0%) vs 2/37 (5.4%). For group A and B platelets, the relatively low rate of HT positive events in both UPP and PPPT precluded meaningful statistical comparison. Testing of 834 additional group O PPPT yielded 6 HT positive components for a total of 9/1393 (0.65%) HT positive group O PPPT (99% CI 0.23-1.43%).

Conclusions

Greater than 99% of pathogen reduced pooled platelets in PAS have low isohemagglutinin titres using a common component-based testing assay. For PPPT, none of the group A or B tested HT positive with 0.65% positivity in group O. The significant reduction in HT positive pooled platelet components with this new manufacturing method confers a greater safety profile when ABO incompatible platelet transfusion cannot be avoided. These findings may impact hospital decisions around inventory management, platelet selection and titre testing.
导言:由于血小板库存有限,必须使用ABO不相容(ABOi)的血小板进行输血,但由于高滴度(HT)异血凝素(ISO)的存在,可能存在急性溶血性输血反应的风险。经补骨脂素处理的血小板池(PPPT)是在血小板添加剂溶液(PAS)中分割 7 个供体水包膜后制成的。PAS 与血浆的比例为 60:40,可对 ISO 水平产生稀释作用。方法对 1001 份 UPP(2022 年 11 月 8 日至 2023 年 2 月 8 日)和 1019 份 PPPT(2023 年 6 月 1 日至 2023 年 8 月 31 日)进行了基于成分的 ISO 滴定,随后又对 834 份 O 组 PPPT(2023 年 9 月 1 日至 2024 年 1 月 19 日)进行了测试,以完善 HT 率估计值。所有测试均在一个实验室进行,采用手动即时旋管法,将等分的血小板上清液与生理盐水以 1:50 的比例稀释,分别对 A1 和 B 细胞进行测试。与 A1 和 B 细胞中的任一种/两种细胞发生凝集即为 HT 阳性结果。比较了 PPPT 与 UPP 的 HT 结果成分比例。结果 在 PAS 的 1019 个 PPPT 中,有 3 个(0.29%)检测出 HT 阳性,且均为 O 组。相比之下,64/1001(6.4%)个 UPP 呈 HT 阳性(P 值为 0.0001)。按 ABO 血型分类,PPPT 与 UPP 的 HT 阳性率分别为:O 组 3/559 (0.54%) vs 53/496(10.6%)(P 值为 <.0001);A 组 0/439(0%) vs 9/468(1.9%);B 组 0/21(0%) vs 2/37(5.4%)。对于 A 组和 B 组血小板,由于 UPP 和 PPPT 中 HT 阳性率相对较低,因此无法进行有意义的统计比较。对另外 834 个 O 组 PPPT 进行检测后发现 6 个 HT 阳性成分,总共有 9/1393 个(0.65%)O 组 PPPT HT 阳性(99% CI 0.23-1.43%)。采用这种新的生产方法后,HT 阳性的血小板成分显著减少,在无法避免 ABO 不相容血小板输注的情况下,安全性更高。这些发现可能会影响医院在库存管理、血小板选择和滴度检测方面的决策。
{"title":"Isohemagglutinin titres: A comparison of pathogen reduced pooled platelets manufactured with platelet additive solution versus untreated pooled platelets","authors":"Melanie Bodnar,&nbsp;Dora Lopes-Carvalho,&nbsp;Tammy Ison,&nbsp;Behr Ehsani-Moghaddam,&nbsp;Cindy Lever,&nbsp;Ilona Resz,&nbsp;Mei Yiep,&nbsp;Shuoyan Ning,&nbsp;Michelle Zeller,&nbsp;Charles Musuka","doi":"10.1016/j.tmrv.2024.150853","DOIUrl":"10.1016/j.tmrv.2024.150853","url":null,"abstract":"<div><h3>Introduction</h3><div>Limitations in platelet inventory necessitate the use of ABO-incompatible (ABOi) platelets for transfusion with possible risk of an acute hemolytic transfusion reaction due to the presence of high titre (HT) isohemagglutinins (ISO). Pooled platelets psoralen-treated (PPPT) are manufactured following the division of 7 donor buffy coats in a platelet additive solution (PAS). The PAS:plasma ratio of 60:40 provides a dilutional effect on ISO levels. The purpose of this study is to compare the proportion of PPPT that test ISO HT positive versus untreated 4 donor platelet pools without PAS (UPP).</div></div><div><h3>Methods</h3><div>Component-based ISO titration was performed on 1001 UPP (November 8 2022-February 8 2023) and 1019 PPPT (June 1 2023-August 31 2023) followed by testing of 834 additional group O PPPT (September 1 2023-January 19 2024) to refine the HT rate estimate. All testing was performed at a single laboratory by a manual immediate spin tube method using an aliquot of platelet supernatant diluted 1:50 with saline tested separately against A1 and B cells. Agglutination with either/both A1 and B cell(s) constituted a positive HT result. The proportion of components with HT results were compared for PPPT vs UPP. Statistical analysis was performed using SAS with <em>P</em>-values calculated using the chi-square method.</div></div><div><h3>Results</h3><div>Of 1019 PPPT in PAS, 3 (0.29%) tested HT positive and all were group O. By comparison, 64/1001 (6.4%) UPP were HT positive (<em>P</em>-value &lt;.0001). The rate of HT positivity by ABO blood group for PPPT vs UPP: Group O 3/559 (0.54%) vs 53/496 (10.6%) (<em>P</em>-value &lt;.0001); Group A 0/439 (0%) vs 9/468 (1.9%); Group B 0/21 (0%) vs 2/37 (5.4%). For group A and B platelets, the relatively low rate of HT positive events in both UPP and PPPT precluded meaningful statistical comparison. Testing of 834 additional group O PPPT yielded 6 HT positive components for a total of 9/1393 (0.65%) HT positive group O PPPT (99% CI 0.23-1.43%).</div></div><div><h3>Conclusions</h3><div>Greater than 99% of pathogen reduced pooled platelets in PAS have low isohemagglutinin titres using a common component-based testing assay. For PPPT, none of the group A or B tested HT positive with 0.65% positivity in group O. The significant reduction in HT positive pooled platelet components with this new manufacturing method confers a greater safety profile when ABO incompatible platelet transfusion cannot be avoided. These findings may impact hospital decisions around inventory management, platelet selection and titre testing.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"38 4","pages":"Article 150853"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Towards Safer Transfusion Therapies: The Role of Non-Inflammatory Fcy Receptor 1 Blockade 实现更安全的输血疗法:非炎症性 Fcy 受体 1 阻断剂的作用
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-11-27 DOI: 10.1016/j.tmrv.2024.150856
Yaima Tundidor Cabado

Introduction

The ongoing need to reduce reliance on intravenous immunoglobulin (IVIg) in treating autoimmune and inflammatory diseases calls for novel, targeted therapeutic strategies. Given the adverse events linked with Fcγ receptor (FcγR) III blockade, this study investigates the therapeutic potential of targeting FcγRI, demonstrated herein to be non-inflammatory, offering a more specific and safer alternative to the generalized action of IVIg.

Objective

This work aims to develop an in vivo anti-FcγRI therapy as a more focused and safer alternative to both IVIg therapy and FcγRIII blockade, with potential implications for improving patient outcomes and quality of life.

Design and Methods

From a phage display library, novel anti-human FcγRI antibodies were selected based on their high affinity and specificity for FcγRI. These antibodies were characterized for their ability to block Fc-FcγRI interactions using a human macrophage cell line and to prevent macrophage-mediated phagocytosis of sensitized red blood cells. The inflammatory nature of anti-FcγRI antibodies, compared to those engaging FcγRIII, was assessed through temperature changes and cytokine responses in FcγR-humanized mice, as well as in C57BL/6 and BALB/c mice, providing a comprehensive safety profile.

Results

We developed five novel anti-human FcγRI antibodies, each demonstrating a significant ability to inhibit FcγRI-mediated phagocytosis in vitro, without eliciting adverse inflammatory responses in vivo. Notably, anti-FcγRI administration did not result in the temperature changes or inflammatory responses observed with anti-FcγRIII, highlighting the non-inflammatory benefits of FcγRI targeting.

Conclusions

Our findings support the development of anti-FcγRI antibodies as a promising, non-inflammatory therapeutic approach for transfusion medicine. This strategy not only has the potential to reduce the dependency on IVIg but also offers a safer and more specific method for modulating the immune response in patients.
导言:在治疗自身免疫性疾病和炎症性疾病时,需要减少对静脉注射免疫球蛋白(IVIg)的依赖,这就需要新颖的靶向治疗策略。鉴于 Fcγ 受体(FcγR)III 阻断剂的不良反应,本研究探讨了靶向 FcγRI 的治疗潜力。设计与方法从噬菌体展示文库中筛选出新型抗人FcγRI抗体,这些抗体对FcγRI具有高亲和力和特异性。利用人体巨噬细胞系鉴定了这些抗体阻断 Fc-FcγRI 相互作用的能力,以及阻止巨噬细胞介导的敏化红细胞吞噬作用的能力。结果我们开发了五种新型抗人 FcγRI 抗体,每种抗体都能在体外显著抑制 FcγRI 介导的吞噬作用,而不会在体内引起不良的炎症反应。值得注意的是,抗 FcγRI 给药不会导致抗 FcγRIII 观察到的体温变化或炎症反应,突出了 FcγRI 靶向的非炎症性优势。这一策略不仅有可能减少对 IVIg 的依赖,还能提供一种更安全、更特异的方法来调节患者的免疫反应。
{"title":"Towards Safer Transfusion Therapies: The Role of Non-Inflammatory Fcy Receptor 1 Blockade","authors":"Yaima Tundidor Cabado","doi":"10.1016/j.tmrv.2024.150856","DOIUrl":"10.1016/j.tmrv.2024.150856","url":null,"abstract":"<div><h3>Introduction</h3><div>The ongoing need to reduce reliance on intravenous immunoglobulin (IVIg) in treating autoimmune and inflammatory diseases calls for novel, targeted therapeutic strategies. Given the adverse events linked with Fcγ receptor (FcγR) III blockade, this study investigates the therapeutic potential of targeting FcγRI, demonstrated herein to be non-inflammatory, offering a more specific and safer alternative to the generalized action of IVIg.</div></div><div><h3>Objective</h3><div>This work aims to develop an in vivo anti-FcγRI therapy as a more focused and safer alternative to both IVIg therapy and FcγRIII blockade, with potential implications for improving patient outcomes and quality of life.</div></div><div><h3>Design and Methods</h3><div>From a phage display library, novel anti-human FcγRI antibodies were selected based on their high affinity and specificity for FcγRI. These antibodies were characterized for their ability to block Fc-FcγRI interactions using a human macrophage cell line and to prevent macrophage-mediated phagocytosis of sensitized red blood cells. The inflammatory nature of anti-FcγRI antibodies, compared to those engaging FcγRIII, was assessed through temperature changes and cytokine responses in FcγR-humanized mice, as well as in C57BL/6 and BALB/c mice, providing a comprehensive safety profile.</div></div><div><h3>Results</h3><div>We developed five novel anti-human FcγRI antibodies, each demonstrating a significant ability to inhibit FcγRI-mediated phagocytosis in vitro, without eliciting adverse inflammatory responses in vivo. Notably, anti-FcγRI administration did not result in the temperature changes or inflammatory responses observed with anti-FcγRIII, highlighting the non-inflammatory benefits of FcγRI targeting.</div></div><div><h3>Conclusions</h3><div>Our findings support the development of anti-FcγRI antibodies as a promising, non-inflammatory therapeutic approach for transfusion medicine. This strategy not only has the potential to reduce the dependency on IVIg but also offers a safer and more specific method for modulating the immune response in patients.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"38 4","pages":"Article 150856"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: Special Issue 2024: Early Career Authors 社论:第 2024 期特刊:早期职业作者。
IF 2.7 2区 医学 Q2 HEMATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-07-06 DOI: 10.1016/j.tmrv.2024.150841
Sunny Dzik , Mike F. Murphy , Jeannie Callum , Zoe McQuilten
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引用次数: 0
期刊
Transfusion Medicine Reviews
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