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Development of molecular sterility assay for rapid quality release of cord blood erythrocytes units for transfusion. 开发分子无菌测定法,用于快速发布输血用脐带血红细胞单位的质量。
IF 2.5 3区 医学
Transfusion Pub Date : 2024-12-08 DOI: 10.1111/trf.18084
Laia Closa, Dinara Samarkanova, Carina Lera, Noemí Gonzalez, Mireia Lloret, Margarita Codinach, Gemma Aran, Jesús Fernandez-Sojo, Francisco Vidal, Maria Gloria Soria, Sergi Querol
{"title":"Development of molecular sterility assay for rapid quality release of cord blood erythrocytes units for transfusion.","authors":"Laia Closa, Dinara Samarkanova, Carina Lera, Noemí Gonzalez, Mireia Lloret, Margarita Codinach, Gemma Aran, Jesús Fernandez-Sojo, Francisco Vidal, Maria Gloria Soria, Sergi Querol","doi":"10.1111/trf.18084","DOIUrl":"https://doi.org/10.1111/trf.18084","url":null,"abstract":"<p><strong>Background: </strong>Umbilical cord blood (CB) units stored in banks are an important source of hematopoietic stem cells for transplantation and other cell therapies. New applications, such as their use in transfusions, require rapid quality release as cord blood red blood cells (CB-RBC) have a shorter shelf life.</p><p><strong>Study design and methods: </strong>This project aims to investigate the most prevalent microbial contaminants in CB preparations and validate a rapid sterility testing strategy for CB-RBC based on an automated system (BACT/ALERT®) in tandem with a molecular assay (real-time PCR) capable of detecting at least 100 CFU/mL of Cutibacterium acnes in CB-RBC to accelerate the detection of the most common slow-growing bacteria.</p><p><strong>Results: </strong>Microbial contamination incidence was assessed by reviewing 4696 CB sterility tests, revealing a positivity rate of 3.4%, with C. acnes being the most common slow-growing pathogen. The BACT/ALERT® system, which was validated according to European Pharmacopeia guidelines, was an appropriate method for sterility testing of CB-RBC, although it required up to 14 days of culture to detect C. acnes when iFAPlus and iFNPlus bottles were used to neutralize antimicrobials. Interestingly, the BACT/ALERT® method detected C. acnes at 30 CFU/mL within 14 days, while real-time PCR identified concentrations ≥65 CFU/mL by Day 4.</p><p><strong>Discussion: </strong>In conclusion, we developed a rapid sterility testing strategy that combines automated culture systems and real-time PCR for early microbial contamination, enhancing CB-RBC shelf life for transfusion and emphasizing the importance of combining detection methods.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795220","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
"Are my blood products coming?": Implementation of a novel blood product tracker in the electronic health record system.
IF 2.5 3区 医学
Transfusion Pub Date : 2024-12-08 DOI: 10.1111/trf.18089
Tina Chai, Connor Hartzell, Randy Winstead, Kirk Krokosky, Kaycie Atchison, Angela Mueller, Erika Hall, Jonathan P Wanderer, Jennifer Andrews
{"title":"\"Are my blood products coming?\": Implementation of a novel blood product tracker in the electronic health record system.","authors":"Tina Chai, Connor Hartzell, Randy Winstead, Kirk Krokosky, Kaycie Atchison, Angela Mueller, Erika Hall, Jonathan P Wanderer, Jennifer Andrews","doi":"10.1111/trf.18089","DOIUrl":"https://doi.org/10.1111/trf.18089","url":null,"abstract":"<p><strong>Background: </strong>Blood transfusions are the most common procedure performed in American hospitals. The steps required for blood product delivery are often misunderstood by providers, leading to numerous phone calls to the blood bank requesting order status. Distracting calls can lengthen turnaround time, especially during blood product or staff shortages. We sought a tool to address these questions and reduce distraction. This study highlights a novel blood tracker tool implemented in the electronic health record (EHR) that allows providers to see their blood order's status.</p><p><strong>Study design and methods: </strong>With a multidisciplinary team of healthcare professionals, we constructed a user-friendly blood tracker highly visible in our EHR. It shows the status of a blood product in real time from \"order printed\" to \"preparing\" to \"on its way.\" We surveyed blood bank technologists to determine if call volume and distraction changed.</p><p><strong>Results: </strong>We counted the number of views per month as a surrogate of usage. The blood tracker was viewed 109,626 times per month on average from January through December 2023. The fraction of technologists who received 21 or more calls per shift decreased by 47%.</p><p><strong>Discussion: </strong>We successfully constructed and implemented a novel blood tracker into our EHR that relays the status of a blood product. It is a highly viewed piece of information in our EHR and decreases blood bank call volume as reported by blood bank technologists. Its success demonstrates that closed-loop communication between the lab and providers regarding blood products is beneficial within our organization and potentially others.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795218","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
Impact of input volume on red cell quality in deglycerolized RBCs using a modified ACP-215 protocol.
IF 2.5 3区 医学
Transfusion Pub Date : 2024-12-08 DOI: 10.1111/trf.18088
Anita Howell, Angela Hill, Wanda Lefresne, Brandie Dennis, Tracey R Turner, Qi-Long Yi, Carly Olafson, Nishaka William, Jason P Acker
{"title":"Impact of input volume on red cell quality in deglycerolized RBCs using a modified ACP-215 protocol.","authors":"Anita Howell, Angela Hill, Wanda Lefresne, Brandie Dennis, Tracey R Turner, Qi-Long Yi, Carly Olafson, Nishaka William, Jason P Acker","doi":"10.1111/trf.18088","DOIUrl":"https://doi.org/10.1111/trf.18088","url":null,"abstract":"<p><strong>Background: </strong>The ACP 215 automated cell processor is used to glycerolize and deglycerolize red cell concentrates (RCCs). Its primary advantage over the COBE 2991, previously used to cryopreserve RCCs, is that it maintains a closed system enabling extended post-thaw expiry. However, it was observed that post-deglycerolization hematocrits (Hct) of units processed with the LN236 kit are markedly lower than those processed using the COBE 2991. Therefore, we intended to determine whether a modified process using a smaller volume deglycerolization kit (LN235) could increase the final Hct with limited deleterious effects on product characteristics.</p><p><strong>Study design and methods: </strong>Two proof-of-concept (POC) studies, conducted to determine the feasibility of using the LN235 processing kit for deglycerolization, identified the necessary modifications to the pre- and post-deglycerolization process, after which a two-part study characterized the modified protocol. The impact of pre-cryopreservation storage duration (7-21 days), input red cell mass, and the type of CPD/SAGM RCC production method (red cell filtration and whole blood filtration) were investigated.</p><p><strong>Results: </strong>Using the LN235 kit in conjunction with a volume reduction step for RCCs with a red cell mass exceeding 180 mL allowed for an ~8% increase in Hct. As expected, slightly lower recoveries were seen for large RCCs due to volume reduction; however, there were no other detrimental outcomes on product quality.</p><p><strong>Conclusions: </strong>Leveraging the LN235 kit, recommended by Haemonetics for units with a red cell mass of ≤180 mL, can be used to increase the post-deglycerolization Hct of RCCs that exceed this volume.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795221","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
Comparison of two inline photopheresis systems: A paired crossover trial.
IF 2.5 3区 医学
Transfusion Pub Date : 2024-12-08 DOI: 10.1111/trf.18090
Nicola Piccirillo, Rossana Putzulu, Federica Fatone, Giuseppina Massini, Sabrina Giammarco, Elisabetta Metafuni, Maria Assunta Limongiello, Patrizia Chiusolo, Simona Sica, Luciana Teofili
{"title":"Comparison of two inline photopheresis systems: A paired crossover trial.","authors":"Nicola Piccirillo, Rossana Putzulu, Federica Fatone, Giuseppina Massini, Sabrina Giammarco, Elisabetta Metafuni, Maria Assunta Limongiello, Patrizia Chiusolo, Simona Sica, Luciana Teofili","doi":"10.1111/trf.18090","DOIUrl":"https://doi.org/10.1111/trf.18090","url":null,"abstract":"<p><strong>Background: </strong>Extracorporeal photopheresis (ECP) has been demonstrated as an effective treatment for graft-versus-host disease (GvHD). The inline system was developed by Therakos in 1987. Recently, Fresenius Kabi implemented an integration of cell separator Amicus and a UVA photoactivation device (Phelix), realizing an inline photopheresis system.</p><p><strong>Study design and methods: </strong>In 2022 we designed a prospective paired crossover trial (NCT05718674) comparing two integrated ECP protocols: Therakos CELLEX and Amicus ECP system. Twenty patients affected by corticosteroid resistant GvHD were submitted to 80 ECP, 40 paired procedures.</p><p><strong>Results: </strong>All procedures were well tolerated, with no significant differences in procedure duration. CELLEX cell product showed higher granulocytes and platelet content, while Amicus cell product exhibited higher enrichment of lymphocytes, resulting in significantly higher MNC purity (92.9% vs. 84%). A significantly higher granulocytes and platelets absolute content was observed in CELLEX cell products, while Amicus cell products showed a significantly higher number of TNCs and MNCs. Differences in granulocyte and platelet content remained significant even after normalization of the data according to blood volume processed. These findings are confirmed by a statistically significant higher CE2% for CELLEX for granulocytes and platelets along with the lack of significant difference observed for TNCs and MNCs.</p><p><strong>Discussion: </strong>Our analysis shows differences in the characteristics of the procedure and the cell product. Anyway, both devices are effective for performing ECP procedure, as they collect a cell product suitable for photopheresis. At present, our results represent the first data set comparing two available inline ECP devices.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795219","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
Effect of the added plasma rinseback on residual cell types in plateletpheresis leukoreduction systems.
IF 2.5 3区 医学
Transfusion Pub Date : 2024-12-05 DOI: 10.1111/trf.18086
Kathleen Kelly, Jeff Finlon, Stefan Fulciniti, Deborah Lee, Micaela Jones, Susanne Marschner
{"title":"Effect of the added plasma rinseback on residual cell types in plateletpheresis leukoreduction systems.","authors":"Kathleen Kelly, Jeff Finlon, Stefan Fulciniti, Deborah Lee, Micaela Jones, Susanne Marschner","doi":"10.1111/trf.18086","DOIUrl":"https://doi.org/10.1111/trf.18086","url":null,"abstract":"<p><strong>Background: </strong>Platelets collected by the Trima Accel apheresis device (Terumo BCT) are automatically leukoreduced through a leukoreduction system (LRS) where WBCs are trapped in a conical-shaped LRS chamber. The content has been used as a valuable source of mononuclear cells for research purposes. In frequent, long-term platelet apheresis donors, lymphopenia has been associated with the use of LRS chambers, and implementation of plasma rinseback at the end of the procedure has been shown to mitigate the depletion of lymphocytes. In this report, the cellular content of the LRS chamber and remaining disposable was characterized with and without plasma rinseback.</p><p><strong>Study design and methods: </strong>Trima disposable sets were obtained from apheresis platelet collections in 100% plasma or 35% plasma/65% PAS with or without plasma rinseback at the end of the collections. Cellular content was drained from the LRS chamber and the disposable and was characterized using a hematology analyzer and flow cytometer to establish total cell counts and proportions of RBC, platelet, and WBC subpopulations.</p><p><strong>Results: </strong>LRS chambers contained approximately 10<sup>9</sup> WBCs, with the majority being lymphocytes and monocytes. The addition of plasma rinseback significantly decreased the number of WBCs remaining in the disposable, thereby increasing the number of WBCs returned to the donor. However, rinseback did not impact the WBC content of the LRS chamber itself.</p><p><strong>Conclusions: </strong>Blood Centers using the Trima Accel instrument may reduce lymphopenia in regular platelet donors by implementing plasma rinseback, while ensuring the cellular content of the LRS chamber intended for research purposes remains unaffected.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787083","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
Planning antepartum directed donations in preparation for neonatal cardiac surgery in the absence of compatible donors.
IF 2.5 3区 医学
Transfusion Pub Date : 2024-12-02 DOI: 10.1111/trf.18087
Marc Bienz, Jessica Constanzo-Yanez, Nadia Baillargeon, Gabriel André Leiva-Torres, Mélissa Boileau, Marc Cloutier, Audrey Laforce-Lavoie, Nancy Robitaille
{"title":"Planning antepartum directed donations in preparation for neonatal cardiac surgery in the absence of compatible donors.","authors":"Marc Bienz, Jessica Constanzo-Yanez, Nadia Baillargeon, Gabriel André Leiva-Torres, Mélissa Boileau, Marc Cloutier, Audrey Laforce-Lavoie, Nancy Robitaille","doi":"10.1111/trf.18087","DOIUrl":"https://doi.org/10.1111/trf.18087","url":null,"abstract":"<p><strong>Background: </strong>Homozygous inheritance of the R<sup>N</sup> haplotype, characterized by the absence of the high frequency antigen Sec, as well as partial C and e antigens, is rare and is associated with potential for alloimmunization. Anti-Sec has been reported to be associated with a risk of delayed hemolytic transfusion reaction and hemolytic disease of the fetus and newborn (HDFN).</p><p><strong>Results: </strong>We report the case of a 36-year-old pregnant woman with known sickle cell trait (SCT) and homozygous for the R<sup>N</sup> haplotype with anti-Sec, anti-c, and anti-e. Morphological ultrasound identified dextro-transposition of the great arteries in the fetus. Neonatal cardiac surgery was planned with cardiopulmonary bypass support. Due to the rarity of this genotype, there were no compatible donors in our registry. For this reason, in addition to two previously glycerolized maternal donations, the mother donated three units during pregnancy and one unit postpartum.</p><p><strong>Discussion: </strong>This case highlights the many complexities for the blood supplier pertaining to organizing blood donations during pregnancy, the risk of leukoreduction failure and jellification during the deglycerolization process of units from donors with rare blood carrying the SCT, as well as planning the rare-blood inventory and managing expiry dates to provide transfusion support during delivery, neonatal surgery, and the postoperative period. This case also exemplifies the importance of a strong partnership between blood suppliers and medical teams.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772691","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
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
Transfusion 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
{"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
Transfusion Pub Date : 2024-12-01 Epub Date: 2024-10-09 DOI: 10.1111/trf.18046
Zhongmei Yi, Chunxi Wu, Yumeng Zhou, Bin Zhang
{"title":"Clinical application of centrifugal-membrane hybrid plasmapheresis in the treatment of hyperlipidemia.","authors":"Zhongmei Yi, Chunxi Wu, Yumeng Zhou, Bin Zhang","doi":"10.1111/trf.18046","DOIUrl":"10.1111/trf.18046","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to clarify the clinical application of centrifugal-membrane hybrid plasmapheresis (CMHP) in the treatment of hyperlipidemia.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":"2345-2352"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393563","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
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
Transfusion 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
{"title":"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.","authors":"Kamphon Intharanut, Piyathida Khumsuk, Sarisa Chidtrakoon, Kantaphon Glab-Ampai, Oytip Nathalang","doi":"10.1111/trf.18053","DOIUrl":"10.1111/trf.18053","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":"2252-2259"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547660","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
Comparison of the efficacy of a generic plerixafor versus Mozobil as adjunct peripheral blood stem cell mobilization agents in multiple myeloma patients. 多发性骨髓瘤患者辅助外周血干细胞动员剂普乐沙福与莫佐比的疗效比较。
IF 2.5 3区 医学
Transfusion Pub Date : 2024-12-01 Epub Date: 2024-10-04 DOI: 10.1111/trf.18033
Shan Yuan, Shelley Chang, Hoim Kim, Shirong Wang
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