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Comparative efficacy of liberal and restrictive blood transfusion strategies in anemic patients with acute myocardial infarction: A systematic review and meta-analysis of randomized controlled trials. 自由和限制性输血策略对急性心肌梗死贫血患者的比较疗效:随机对照试验的系统回顾和荟萃分析。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-22 DOI: 10.1111/trf.18110
Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam

Introduction: Acute myocardial infarction (AMI) poses a significant global health burden, warranting meticulous management strategies, particularly in patients with concurrent anemia. Blood transfusion strategies play a pivotal role in optimizing oxygen delivery while minimizing transfusion-related risks. Two contrasting approaches, liberal and restrictive transfusion strategies, have emerged, yet their comparative effectiveness remains uncertain due to conflicting evidence.

Methods: We conducted a systematic review and meta-analysis focusing on randomized controlled trials (RCTs) comparing liberal versus restrictive transfusion strategies in AMI patients with anemia (hemoglobin levels <10 g/dL). Comprehensive searches were performed across electronic databases up to March 31, 2024. Data extraction, risk of bias assessment using Cochrane's RoB 2 tool, and meta-analysis were conducted following methodology.

Results: Among 327 initially identified studies, four high-quality RCTs met the inclusion criteria. These trials encompassed varied sample sizes and patient demographics. Meta-analysis revealed no significant difference in 30-day all-cause mortality nor recurrent MI between liberal and restrictive transfusion strategies. However, combining these outcomes into a composite measure demonstrated a significant reduction favoring liberal transfusion (pooled odds ratio = 0.82; 95% confidence interval = 0.69-0.99).

Conclusion: While liberal transfusion strategies show promise in reducing adverse outcomes, clinical decision-making should be guided by individual patient factors and preferences. Personalized care remains paramount in determining the most appropriate transfusion approach for AMI patients with anemia. Further research is warranted to elucidate the optimal transfusion strategy in this population.

急性心肌梗死(AMI)是一个重大的全球健康负担,需要细致的管理策略,特别是对并发贫血的患者。输血策略在优化氧气输送同时最小化输血相关风险方面发挥着关键作用。已经出现了两种截然不同的方法,自由输血策略和限制性输血策略,但由于证据相互矛盾,它们的相对有效性仍然不确定。方法:我们进行了一项系统回顾和荟萃分析,重点关注随机对照试验(rct),比较自由输血与限制性输血策略在AMI贫血患者(血红蛋白水平)中的作用。结果:在327项初步确定的研究中,有4项高质量的rct符合纳入标准。这些试验包括不同的样本量和患者人口统计数据。荟萃分析显示,自由和限制性输血策略在30天全因死亡率和复发性心肌梗死方面没有显著差异。然而,将这些结果合并为一个综合测量显示,自由输血显著减少(合并优势比= 0.82;95%置信区间= 0.69-0.99)。结论:虽然自由输血策略有望减少不良后果,但临床决策应根据患者的个体因素和偏好进行指导。个性化护理仍然是确定最适合AMI患者贫血输血方法的关键。需要进一步的研究来阐明这一人群的最佳输血策略。
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引用次数: 0
How do we engage with the lesbian, gay, bisexual, and transgender community in blood donation and research? Reflections from the Assessing Donor Variability and New Concepts in Eligibility study. 我们如何在献血和研究中与女同性恋、男同性恋、双性恋和跨性别群体合作?供体变异性评估的思考与合格性研究的新概念。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-22 DOI: 10.1111/trf.18098
Lauren A Crowder, Rita Reik, Susan L Stramer, Barbee I Whitaker, Renata Buccheri, Karla G Zurita, Nick Gehrig, Susan Forbes, Rodney Wilson, Suchitra Pandey, Brian Custer

Background: The Assessing Donor Variability and New Concepts in Eligibility (ADVANCE) study was a multicenter cross-organizational collaboration to collect data to inform possible changes in blood donor selection criteria for men who have sex with men. Multiple recruitment approaches were used, and these may be applicable to current efforts in LGBTQ+ community engagement to recruit new blood donors.

Methods: Fieldwork for ADVANCE was a partnership between blood collection organizations (BCOs) and LGBTQ+ community organizations. First, we had to establish relationships with these organizations based on trust and commitment to common objectives. We developed recruitment materials for online and printed distribution. We worked directly with organizations in each community to tailor outreach. Approaches changed over the course of the COVID-19 pandemic.

Results: The study website was a portal for general information about donation policy, the study itself, scheduling study visits, and news stories. It was important to evolve outreach messages and approaches over time. Study team members created changing content and posting schedules on the website and social media platforms. We also worked with community and social media influencers to raise community awareness about the study. Later in the pandemic, we were able to recruit at in-person community events. These in-person events were our most successful outreach.

Discussion: The partnerships with LGBTQ+ community organizations, diversity promotion groups, and other members of the community were instrumental in making ADVANCE a success. The approaches we used for the study may be valuable for BCO outreach to attract new blood donors.

背景:评估献血者可变性和资格新概念(ADVANCE)研究是一项多中心跨组织合作的研究,旨在收集数据,告知男男性行为者的献血者选择标准可能发生的变化。使用了多种招募方法,这些方法可能适用于当前LGBTQ+社区参与招募新献血者的努力。方法:ADVANCE的现场工作是由采血组织(BCOs)和LGBTQ+社区组织合作进行的。首先,我们必须在信任和对共同目标的承诺的基础上与这些组织建立关系。我们制作了网上和印刷的招聘材料。我们直接与每个社区的组织合作,量身定制外展服务。在COVID-19大流行期间,方法发生了变化。结果:研究网站是关于捐赠政策、研究本身、研究访问安排和新闻报道的一般信息的门户。随着时间的推移,发展外联信息和方法是很重要的。研究小组成员在网站和社交媒体平台上创建了不断变化的内容和发布时间表。我们还与社区和社交媒体影响者合作,提高社区对这项研究的认识。在大流行后期,我们能够在面对面的社区活动中招募人员。这些面对面的活动是我们最成功的外联活动。讨论:与LGBTQ+社区组织、多元化促进团体和其他社区成员的合作对ADVANCE的成功起到了重要作用。我们在研究中使用的方法可能对BCO吸引新献血者的推广有价值。
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引用次数: 0
Quantifying the impact of a novel virus on the economic value of pathogen reduction technology for platelets. 量化一种新病毒对血小板病原体减少技术经济价值的影响。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-19 DOI: 10.1111/trf.18115
Adam Irving, Peter Simmonds, William Irving, Stephen Thomas, James Neuberger

Background: Pathogen reduction technology (PRT) is an intervention designed to proactively reduce the amount of known and unknown pathogens in donated blood. As current screening for known pathogens is highly effective, some previous evaluations have found that the value of PRT largely hinges on a previously unknown pathogen, most likely a novel virus, emerging and entering the blood supply. In such situations, the risk of emergence can and should be modeled and presented transparently in the cost-effectiveness results for deliberation by decision-makers.

Study design and methods: We built a Markov cohort model assessing the economic value of introducing PRT for platelets in the United Kingdom. Input data were obtained from the existing PRT literature, national sources, or by conservative assumption. The primary objective of the study was to demonstrate methods for modeling and presenting the risk of emergence of a novel virus, using alternative time-to-emergence scenarios in the probabilistic sensitivity analysis.

Results: As expected, PRT will be more cost-effective the sooner the novel virus emerges after the introduction of PRT. In the base-case cost scenario, the deterministic ICER was £270 K/QALY gained if the virus emerged immediately and rose to £3.3 M/QALY gained if the virus emerged after 25 years.

Discussion: At current prices, PRT is unlikely to be cost-effective when judged against thresholds for medicines and treatments. Given significant additional willingness-to-pay for blood safety, PRT is only likely to be cost-effective if a novel virus that causes chronic infection with significant morbidity and mortality emerges very soon after the introduction of PRT.

背景:病原体减少技术(PRT)是一种旨在主动减少捐献血液中已知和未知病原体数量的干预措施。由于目前对已知病原体的筛查非常有效,一些先前的评估发现,PRT的价值在很大程度上取决于以前未知的病原体,很可能是一种新的病毒,出现并进入血液供应。在这种情况下,可以而且应该对出现的风险进行建模,并在成本效益结果中透明地提出,供决策者审议。研究设计和方法:我们建立了一个马尔可夫队列模型,评估在英国引入血小板PRT的经济价值。输入数据来自现有的PRT文献、国家来源或保守假设。该研究的主要目的是演示在概率敏感性分析中使用替代出现时间情景建模和呈现新型病毒出现风险的方法。结果:正如预期的那样,在引入PRT后,新型病毒出现得越快,PRT的成本效益越高。在基本情况成本情景中,如果病毒立即出现,确定性风险成本为270万英镑/质量效益,如果病毒在25年后出现,则风险成本上升至330万英镑/质量效益。讨论:以目前的价格,根据药物和治疗的阈值判断,PRT不太可能具有成本效益。考虑到为血液安全付费的意愿大大增加,只有在采用PRT后不久就出现一种导致慢性感染并具有显著发病率和死亡率的新型病毒时,PRT才可能具有成本效益。
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引用次数: 0
Evolving patterns of first blood product use in trauma in the era of hemorrhage control resuscitation. 在出血控制复苏时代,创伤中首次血液制品使用的演变模式。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-17 DOI: 10.1111/trf.18100
Maryam Asif, Safee U Haider, Zhinan Liu, Lynn G Stansbury, John R Hess

Background: We reviewed trauma blood use at our US regional trauma center 2011-2022-including PROPPR trial participation 2012-2014 and initiation of whole blood availability in 2019-to assess the implementation of early coagulation support in acute trauma care.

Study design/methods: We identified all acute trauma patients recorded by our Trauma Registry as arriving at our large US regional Level 1 trauma center from April 6, 2011 (Blood Bank opening) through December 2022. Patient cohort data were then linked directly to Blood Bank final-product-issue date/time data to identify patients receiving any blood product in the first 24 h of care and then, specifically, at least one unit of Red Blood Cells (RBC), Plasma, or Whole Blood (WB). Results were binned as: "RBC first," "Plasma first," "Both at the same time," or "WB first."

Results: Over the study period, 73,634 acute trauma patients received care, and 12,927 received at least one unit of a blood product. The proportion receiving plasma or a combination of plasma and RBCs as the initial transfusion increased after 2015 from 33% to 66%, while the proportion receiving packed RBCs alone decreased from 57% to about 18%. Since its introduction in 2019, the use of WB as the first product has grown to 20%.

Conclusions: This retrospective cohort study documents the increasing use of plasma and now WB as initial products issued in trauma resuscitation, reflecting acceptance of coagulation support as the standard of care and the use of hemostatic resuscitation protocols.

背景:我们回顾了美国地区创伤中心 2011-2022 年的创伤用血情况--包括 2012-2014 年参与 PROPPR 试验和 2019 年开始提供全血--以评估急性创伤护理中早期凝血支持的实施情况:我们确定了由创伤登记处记录的从 2011 年 4 月 6 日(血库开放)到 2022 年 12 月期间抵达我们美国大型地区一级创伤中心的所有急性创伤患者。然后将患者队列数据与血库最终产品发放日期/时间数据直接关联起来,以确定在护理的前 24 小时内接受过任何血液产品的患者,特别是至少接受过一个单位的红细胞(RBC)、血浆或全血(WB)的患者。结果分为以下几类"先用红细胞"、"先用血浆"、"同时用两种 "或 "先用全血":在研究期间,73634 名急性创伤患者接受了治疗,其中 12927 人接受了至少一个单位的血液制品。2015年后,接受血浆或血浆与红细胞组合作为首次输血的比例从33%增至66%,而仅接受包装红细胞的比例从57%降至约18%。自2019年引入WB作为首批产品以来,使用WB的比例已增至20%:这项回顾性队列研究记录了在创伤复苏中越来越多地使用血浆和现在的 WB 作为首发产品,这反映了凝血支持被接受为护理标准以及止血复苏方案的使用。
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引用次数: 0
Biotinylation of human platelets is compatible with pathogen inactivation treatment and cold storage for clinical studies. 人血小板的生物素化与病原体灭活治疗和临床研究的冷藏是相容的。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-17 DOI: 10.1111/trf.18102
Charlotte Muret, David Crettaz, Agathe Martin, Alessandro Aliotta, Debora Bertaggia Calderara, Lorenzo Alberio, Michel Prudent

Background: Production of platelet concentrates (PCs) involves several steps that significantly affect platelet behavior. To gain a deeper understanding of how storage conditions impact donor platelet recirculation and functionality post-transfusion, ex vivo platelet labeling is a feasible approach. However, before pursuing clinical investigations of platelet recirculation and function in humans, we aimed to determine the effects of pathogen inactivation technology (PIT) and storage conditions (4°C vs. room temperature [RT]) on phenotype and function of biotinylated platelets compared to conventional PIT PCs for transfusion.

Methods: Nine PCs were prepared in 61% additive solution from 45 buffy coats (five buffy coats each). A pool-and-split of three units was used to prepare three equivalent PCs: two labeled with biotin and stored at RT or 4°C, and one without labeling and stored at RT. All PCs were then treated by PIT (amotosalen/UVA) and stored for 14 days. Labeling efficiency, platelet concentration, metabolic parameters, aggregation response (ADP, collagen, co-aggregation with epinephrine), and platelet phenotype (CD42b, CD62-P, phosphatidylserine) at the basal stage and upon stimulation (ADP or TRAP-6) were performed.

Results: Labeling efficiency of PIT and 4°C PCs was stable over 14 days of storage. Differences in platelet function and phenotype were mainly due to the storage temperature and not the biotinylation process. Phenotypes at baseline or after stimulation were equivalent in biotin-positive and biotin-negative platelets.

Conclusion: Biotin-labeled platelets can effectively enable investigation of the effects of PIT and storage temperature for clinical studies. This method shows great potential for improving platelet transfusion knowledge.

背景:血小板浓缩物(PCs)的生产涉及多个步骤,这些步骤会对血小板的行为产生重大影响。为了深入了解储存条件如何影响供体血小板的再循环和输血后的功能,体内外血小板标记是一种可行的方法。然而,在对人体血小板再循环和功能进行临床研究之前,我们旨在确定病原体灭活技术(PIT)和储存条件(4°C 与室温 [RT])对生物素化血小板表型和功能的影响,并与用于输血的传统 PIT PCs 进行比较:用 61% 的添加剂溶液从 45 个水样(每个水样 5 个)中制备出 9 个 PC。用三个单位的集合拆分法制备三个等量的 PC:两个用生物素标记并在 RT 或 4°C 下保存,另一个未标记并在 RT 下保存。然后用 PIT(amotosalen/UVA)处理所有 PC,并保存 14 天。对基础阶段和刺激(ADP 或 TRAP-6)时的标记效率、血小板浓度、代谢参数、聚集反应(ADP、胶原蛋白、与肾上腺素共同聚集)和血小板表型(CD42b、CD62-P、磷脂酰丝氨酸)进行了测定:结果:PIT 和 4°C PCs 的标记效率在储存 14 天后保持稳定。血小板功能和表型的差异主要是储存温度造成的,而不是生物素化过程造成的。生物素阳性和生物素阴性血小板在基线或刺激后的表型相同:结论:生物素标记血小板可有效地调查 PIT 和储存温度对临床研究的影响。这种方法在提高血小板输注知识方面显示出巨大潜力。
{"title":"Biotinylation of human platelets is compatible with pathogen inactivation treatment and cold storage for clinical studies.","authors":"Charlotte Muret, David Crettaz, Agathe Martin, Alessandro Aliotta, Debora Bertaggia Calderara, Lorenzo Alberio, Michel Prudent","doi":"10.1111/trf.18102","DOIUrl":"https://doi.org/10.1111/trf.18102","url":null,"abstract":"<p><strong>Background: </strong>Production of platelet concentrates (PCs) involves several steps that significantly affect platelet behavior. To gain a deeper understanding of how storage conditions impact donor platelet recirculation and functionality post-transfusion, ex vivo platelet labeling is a feasible approach. However, before pursuing clinical investigations of platelet recirculation and function in humans, we aimed to determine the effects of pathogen inactivation technology (PIT) and storage conditions (4°C vs. room temperature [RT]) on phenotype and function of biotinylated platelets compared to conventional PIT PCs for transfusion.</p><p><strong>Methods: </strong>Nine PCs were prepared in 61% additive solution from 45 buffy coats (five buffy coats each). A pool-and-split of three units was used to prepare three equivalent PCs: two labeled with biotin and stored at RT or 4°C, and one without labeling and stored at RT. All PCs were then treated by PIT (amotosalen/UVA) and stored for 14 days. Labeling efficiency, platelet concentration, metabolic parameters, aggregation response (ADP, collagen, co-aggregation with epinephrine), and platelet phenotype (CD42b, CD62-P, phosphatidylserine) at the basal stage and upon stimulation (ADP or TRAP-6) were performed.</p><p><strong>Results: </strong>Labeling efficiency of PIT and 4°C PCs was stable over 14 days of storage. Differences in platelet function and phenotype were mainly due to the storage temperature and not the biotinylation process. Phenotypes at baseline or after stimulation were equivalent in biotin-positive and biotin-negative platelets.</p><p><strong>Conclusion: </strong>Biotin-labeled platelets can effectively enable investigation of the effects of PIT and storage temperature for clinical studies. This method shows great potential for improving platelet transfusion knowledge.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Enhanced oxygen availability and preserved aggregative function in platelet concentrates stored at reduced platelet concentration. 在血小板浓度降低的情况下,血小板浓缩物的氧可用性增强,聚集功能得以保存。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-14 DOI: 10.1111/trf.18101
Jamie Nash, Dean Pym, A Davies, Christine Saunders, Chloe George, J O Williams, O Y Grinberg, Philip E James

Background: Storage of platelets as platelet concentrates for transfusion is limited to 7 days in the United Kingdom due to deleterious effects on platelet quality and function that occur over time. Oxygen (O2) availability and sufficient gaseous exchange are known to be essential in maintaining the viability and function of platelets stored for transfusion. Despite this, there is a paucity of studies undertaking direct measures of O2 and optimization of conditions throughout storage. We address this and modulate the storage conditions to improve platelet quality and function.

Study design and methods: Electron paramagnetic resonance oximetry was implemented to directly measure the [O2] experienced by stored platelet concentrates and the O2 consumption rate under standard blood banking conditions. From these direct measures the mathematical modeling was then applied to predict the main parameters contributing to effective O2 distribution throughout the unit.

Results: This study demonstrates reducing the storage [O2] to reflect near physiological levels significantly alters O2 distribution within the unit and negatively impacts platelet functionality and quality, and therefore is not a viable storage option.

Discussion: We show the reduction of platelet concentration within a unit improves O2 availability and pH, promotes a more uniform distribution of O2 throughout prolonged storage, and maintains platelet agonist-induced aggregation comparable to 100% platelet concentration. This may be a viable option and could potentially lead to reduced donor demand.

背景:由于血小板的质量和功能会随着时间的推移而受到有害影响,因此在英国,作为浓缩血小板的血小板的输血贮存时间限制为 7 天。众所周知,氧气(O2)的可用性和充分的气体交换对维持储存用于输血的血小板的活力和功能至关重要。尽管如此,在整个储存过程中直接测量氧气和优化储存条件的研究却很少。研究设计和方法:研究设计:采用电子顺磁共振血氧仪直接测量储存血小板浓缩物的[O2]和标准血库条件下的氧气消耗率。然后根据这些直接测量结果,应用数学建模方法预测有助于氧气在整个装置中有效分布的主要参数:结果:这项研究表明,降低贮存[O2]以反映接近生理水平会显著改变血库内的氧气分布,并对血小板的功能和质量产生负面影响,因此不是一种可行的贮存方案:我们的研究表明,降低单位内血小板浓度可改善氧气的可用性和 pH 值,促进氧气在整个长期储存过程中更均匀地分布,并保持与 100%血小板浓度相当的血小板激动剂诱导聚集。这可能是一个可行的选择,并有可能减少对捐献者的需求。
{"title":"Enhanced oxygen availability and preserved aggregative function in platelet concentrates stored at reduced platelet concentration.","authors":"Jamie Nash, Dean Pym, A Davies, Christine Saunders, Chloe George, J O Williams, O Y Grinberg, Philip E James","doi":"10.1111/trf.18101","DOIUrl":"https://doi.org/10.1111/trf.18101","url":null,"abstract":"<p><strong>Background: </strong>Storage of platelets as platelet concentrates for transfusion is limited to 7 days in the United Kingdom due to deleterious effects on platelet quality and function that occur over time. Oxygen (O<sub>2</sub>) availability and sufficient gaseous exchange are known to be essential in maintaining the viability and function of platelets stored for transfusion. Despite this, there is a paucity of studies undertaking direct measures of O<sub>2</sub> and optimization of conditions throughout storage. We address this and modulate the storage conditions to improve platelet quality and function.</p><p><strong>Study design and methods: </strong>Electron paramagnetic resonance oximetry was implemented to directly measure the [O<sub>2</sub>] experienced by stored platelet concentrates and the O<sub>2</sub> consumption rate under standard blood banking conditions. From these direct measures the mathematical modeling was then applied to predict the main parameters contributing to effective O<sub>2</sub> distribution throughout the unit.</p><p><strong>Results: </strong>This study demonstrates reducing the storage [O<sub>2</sub>] to reflect near physiological levels significantly alters O<sub>2</sub> distribution within the unit and negatively impacts platelet functionality and quality, and therefore is not a viable storage option.</p><p><strong>Discussion: </strong>We show the reduction of platelet concentration within a unit improves O<sub>2</sub> availability and pH, promotes a more uniform distribution of O<sub>2</sub> throughout prolonged storage, and maintains platelet agonist-induced aggregation comparable to 100% platelet concentration. This may be a viable option and could potentially lead to reduced donor demand.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The potential of plasma exchange in treating Chronic Fatigue Syndrome and long COVID: Targeting autoimmune and inflammatory mechanisms. 血浆置换在治疗慢性疲劳综合征和长期 COVID 方面的潜力:针对自身免疫和炎症机制。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-14 DOI: 10.1111/trf.18099
Yamac Akgun
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引用次数: 0
Serological and molecular characterization of novel ABO variants including an interesting B(A) subgroup. 新型 ABO 变体的血清学和分子特征,包括一个有趣的 B(A)亚群。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-07 DOI: 10.1111/trf.18039
Yunlei He, Lu Yu, Jiwei Zhang, Yiwen He, Di Niu, Gang Deng

Background: ABO grouping is the most important pretransfusion testing that is directly related to the safety of blood transfusion. A weak ABO subgroup is one of the important causes of an ABO grouping discrepancy. Here, we investigated the characterization of four novel ABO variants including a novel B(A) subgroup.

Study design and methods: RBCs were phenotyped by standard serology methods. The full coding regions of the ABO gene and the erythroid cell-specific regulatory elements in intron one were sequenced. The effect of the possible splice site variant was predicted by Alamut software. The 3D structural modeling of three relative B(A) enzymes (p.Met214Thr, p.Met214Val, and p.Met214Leu) were performed by PyMOL software.

Results: Four novel ABO alleles were identified with weak ABO expression in this study, in which two would lead to premature terminations, and two resulted in amino acid changes. In silico analysis revealed that the splice site variant c.155G>T had the potential to alter splice transcripts. 3D structural view shown that the variant amino acid position 214 was spatially adjacent to the donor recognition pocket residues (266Met and 268Ala) and just next to the 211DVD213 motif. The size of the side chain of Thr and Val is the smallest, Leu is medium, and Met is the largest, and the size changes in the critical position 214 may affect the donor recognition pocket.

Conclusion: Four ABO subgroup alleles were newly linked to different kinds of ABO variants and the possible mechanism through which they produce weak ABO subgroups was analyzed in silico.

背景:ABO 血型是输血前最重要的检测项目,直接关系到输血的安全性。ABO亚群薄弱是导致ABO血型不一致的重要原因之一。在此,我们研究了四种新型 ABO 变异的特征,其中包括一种新型 B(A)亚群:研究设计与方法:采用标准血清学方法对红细胞进行表型分析。对 ABO 基因的全部编码区和内含子一的红细胞特异性调控元件进行了测序。Alamut 软件预测了可能的剪接位点变异的影响。用 PyMOL 软件对三种相对 B(A)酶(p.Met214Thr、p.Met214Val 和 p.Met214Leu)进行了三维结构建模:结果:本研究发现了四种新型 ABO 等位基因,它们的 ABO 表达较弱,其中两种等位基因会导致过早终止,两种等位基因会导致氨基酸变化。硅学分析表明,剪接位点变异 c.155G>T 有可能改变剪接转录本。三维结构视图显示,变异氨基酸位置 214 在空间上与供体识别袋残基(266Met 和 268Ala)相邻,并且紧挨着 211DVD213 主题。Thr和Val的侧链大小最小,Leu中等,Met最大,关键位置214的大小变化可能会影响供体识别袋:结论:四种 ABO 亚群等位基因与不同类型的 ABO 变异有新的联系,并对它们产生弱 ABO 亚群的可能机制进行了硅学分析。
{"title":"Serological and molecular characterization of novel ABO variants including an interesting B(A) subgroup.","authors":"Yunlei He, Lu Yu, Jiwei Zhang, Yiwen He, Di Niu, Gang Deng","doi":"10.1111/trf.18039","DOIUrl":"10.1111/trf.18039","url":null,"abstract":"<p><strong>Background: </strong>ABO grouping is the most important pretransfusion testing that is directly related to the safety of blood transfusion. A weak ABO subgroup is one of the important causes of an ABO grouping discrepancy. Here, we investigated the characterization of four novel ABO variants including a novel B(A) subgroup.</p><p><strong>Study design and methods: </strong>RBCs were phenotyped by standard serology methods. The full coding regions of the ABO gene and the erythroid cell-specific regulatory elements in intron one were sequenced. The effect of the possible splice site variant was predicted by Alamut software. The 3D structural modeling of three relative B(A) enzymes (p.Met214Thr, p.Met214Val, and p.Met214Leu) were performed by PyMOL software.</p><p><strong>Results: </strong>Four novel ABO alleles were identified with weak ABO expression in this study, in which two would lead to premature terminations, and two resulted in amino acid changes. In silico analysis revealed that the splice site variant c.155G>T had the potential to alter splice transcripts. 3D structural view shown that the variant amino acid position 214 was spatially adjacent to the donor recognition pocket residues (266Met and 268Ala) and just next to the <sup>211</sup>DVD<sup>213</sup> motif. The size of the side chain of Thr and Val is the smallest, Leu is medium, and Met is the largest, and the size changes in the critical position 214 may affect the donor recognition pocket.</p><p><strong>Conclusion: </strong>Four ABO subgroup alleles were newly linked to different kinds of ABO variants and the possible mechanism through which they produce weak ABO subgroups was analyzed in silico.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":"2364-2370"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Clinical application of centrifugal-membrane hybrid plasmapheresis in the treatment of hyperlipidemia. 离心-膜混合血浆置换术在治疗高脂血症中的临床应用。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-09 DOI: 10.1111/trf.18046
Zhongmei Yi, Chunxi Wu, Yumeng Zhou, Bin Zhang

Objective: This study aimed to clarify the clinical application of centrifugal-membrane hybrid plasmapheresis (CMHP) in the treatment of hyperlipidemia.

Methods: A retrospective study was conducted on 48 patients who were diagnosed with hyperlipidemia and had received CMHP treatment. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were monitored, and adverse reactions to the treatment were observed.

Results: Forty-eight patients with hyperlipidemia received CMHP over 59 sessions. The average age of the 48 patients with hyperlipidemia, including 32 males (66.67%) and 16 females (33.33%), was 44.23 ± 12.02 years. Twenty-nine outpatients (60.42%) and 19 inpatients (39.58%) were included. Hypertriglyceridemia was diagnosed in 16 cases (33.33%), mixed hyperlipidemia in 31 cases (64.58%), and hypercholesterolemia in one case (2.08%). The pretreatment blood lipid concentrations were significantly different after the 59 CMHP treatments (p < .001). The concentrations of TC, TG, HDL-C, and LDL-C decreased significantly after the treatment, and the median ratios of reduction were 67.06% (range: 58.97%-71.87%), 63.33% (range: 55.20%-74.86%), 45.87% (range: 35.86%-52.95%), and 66.09% (range: 44.37%-73.94%), respectively. Three adverse reactions (5.08%) were recorded. No differences were detected in therapeutic parameters, effects, or adverse reactions between the two blood cell separators, there was no difference in Lipoprotein apheresis efficacy.

Conclusion: This preliminary study demonstrated the clinical application of CMHP in patients in the treatment of hyperlipidemia. However, further studies are needed applying CMHP with hyperlipidemia.

研究目的本研究旨在明确离心-膜混合血浆置换术(CMHP)在治疗高脂血症中的临床应用:方法:对 48 例确诊为高脂血症并接受过 CMHP 治疗的患者进行回顾性研究。监测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C),并观察治疗的不良反应:48 名高脂血症患者接受了 CMHP 59 次治疗。48 名高脂血症患者的平均年龄为 44.23±12.02 岁,其中男性 32 人(66.67%),女性 16 人(33.33%)。其中门诊患者 29 人(60.42%),住院患者 19 人(39.58%)。16例(33.33%)被诊断为高甘油三酯血症,31例(64.58%)被诊断为混合型高脂血症,1例(2.08%)被诊断为高胆固醇血症。经过 59 次 CMHP 治疗后,治疗前的血脂浓度有明显差异(P 结论:CMHP 是一种治疗高脂血症的新方法:这项初步研究证明了 CMHP 在治疗高脂血症患者中的临床应用。然而,还需要对 CMHP 在高脂血症中的应用进行进一步研究。
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引用次数: 0
Identification of two novel variants, c.-35A>T and c.[-35A>T, 725T>G], in the FUT1 gene in a patient exhibiting the para-Bombay phenotype. 在一名表现出准孟买表型的患者体内发现 FUT1 基因中的两个新型变异体:c.-35A>T 和 c.[-35A>T, 725T>G]。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI: 10.1111/trf.18053
Kamphon Intharanut, Piyathida Khumsuk, Sarisa Chidtrakoon, Kantaphon Glab-Ampai, Oytip Nathalang

Background: Reduced or absent H antigens on red cells with the (para-)Bombay phenotype can arise from FUT1 gene mutations, impacting the structure and function of 1,2-L-fucosyltransferase 1 (1,2-L-FucT1). Here, we identified the novel mutations in one patient displaying the para-Bombay phenotype and examined the potential molecular mechanisms underlying this phenotype.

Materials and methods: ABH antigens and antibodies were detected in patient's blood and saliva using serological methods. The genotypes of ABO, FUT1, and FUT2 were imputed using the genetic variations discovered in the whole exome sequencing data. Three-dimensional (3D) models of FUT1 variants were built using Deepmind's AlphaFold2 and HDOCK, and the possible effects of the variants were predicted to evaluate using DynaMut2 and Polyphen-2.

Results: Serological analysis confirmed the para-Bombay B phenotype producing anti-HI and exhibiting normal genotypes ABO*B.01/O.01.02 and FUT2*01.09/01.09. Remarkably, the phenotype is caused by a compound heterozygous genotype: one allele containing the novel c.-35A>T mutation and the known c.725T>G mutation (p.Leu242Arg) of FUT1, and the other allele containing the c.-35A>T mutation. From the computerized stimulation analysis, p.Arg242 of the FUT1 variant may be detrimental, destabilizing, and probably damaging to 1,2-L-FucT1, although not altering the 3D structure of the entire enzyme. The c.-35A>T promoter DNA left at the binding interface of both ZID and c-Rel transcription factors may enable regulation of 1,2-L-FucT1 function at gene promoters.

Conclusion: We identified the two novel variants, c.-35A>T and c.[-35A>T, 725T>G], in the FUT1 causing the para-Bombay phenotype. This finding may clarify the molecular mechanisms and enhance blood transfusion safety.

背景:FUT1基因突变会影响1,2-L-岩藻糖基转移酶1(1,2-L-FucT1)的结构和功能,从而导致(副)孟买表型红细胞上的H抗原减少或缺失。在此,我们确定了一名显示副孟买表型的患者的新型突变,并研究了这种表型的潜在分子机制:采用血清学方法检测患者血液和唾液中的 ABH 抗原和抗体。利用全外显子组测序数据中发现的基因变异来推算 ABO、FUT1 和 FUT2 的基因型。利用 Deepmind 的 AlphaFold2 和 HDOCK 建立了 FUT1 变异的三维(3D)模型,并利用 DynaMut2 和 Polyphen-2 预测评估了变异的可能影响:血清学分析证实,副孟买B表型产生抗-HI,基因型ABO*B.01/O.01.02和FUT2*01.09/01.09正常。值得注意的是,这种表型是由复合杂合基因型引起的:一个等位基因含有 FUT1 的新型 c.-35A>T 突变和已知的 c.725T>G 突变(p.Leu242Arg),另一个等位基因含有 c.-35A>T 突变。从计算机刺激分析来看,FUT1 变体中的 p.Arg242 可能对 1,2-L-FucT1有害,破坏其稳定性,并可能造成损害,尽管不会改变整个酶的三维结构。在ZID和c-Rel转录因子的结合界面上留下的c.-35A>T启动子DNA可能使1,2-L-FucT1的功能在基因启动子上得到调控:我们在 FUT1 中发现了两个新变异,c.-35A>T 和 c.[-35A>T,725T>G],这两个变异导致了副孟买表型。这一发现可能会阐明分子机制并提高输血安全性。
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Transfusion
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