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.
{"title":"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.","authors":"Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam","doi":"10.1111/trf.18110","DOIUrl":"https://doi.org/10.1111/trf.18110","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878021","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}
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.
{"title":"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.","authors":"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","doi":"10.1111/trf.18098","DOIUrl":"https://doi.org/10.1111/trf.18098","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878026","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}
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.
{"title":"Quantifying the impact of a novel virus on the economic value of pathogen reduction technology for platelets.","authors":"Adam Irving, Peter Simmonds, William Irving, Stephen Thomas, James Neuberger","doi":"10.1111/trf.18115","DOIUrl":"https://doi.org/10.1111/trf.18115","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Study design and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855490","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}
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.
{"title":"Evolving patterns of first blood product use in trauma in the era of hemorrhage control resuscitation.","authors":"Maryam Asif, Safee U Haider, Zhinan Liu, Lynn G Stansbury, John R Hess","doi":"10.1111/trf.18100","DOIUrl":"https://doi.org/10.1111/trf.18100","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Study design/methods: </strong>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.\"</p><p><strong>Results: </strong>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%.</p><p><strong>Conclusions: </strong>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.</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":"142839911","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}
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.
{"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}
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.
{"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}
{"title":"The potential of plasma exchange in treating Chronic Fatigue Syndrome and long COVID: Targeting autoimmune and inflammatory mechanisms.","authors":"Yamac Akgun","doi":"10.1111/trf.18099","DOIUrl":"https://doi.org/10.1111/trf.18099","url":null,"abstract":"","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":"142824437","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}
Pub Date : 2024-12-01Epub Date: 2024-10-07DOI: 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.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-10-09DOI: 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.
{"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}
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.
{"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}