Mithun Nelliat, G. Mohan, J. Lukose, S. Shastry, S. Chidangil
Background: Raman tweezers spectroscopy (RTS) is a powerful tool that combines optical tweezers and Raman spectroscopy to study single living cells. RTS has become increasingly popular in biomedical and clinical research due to its high molecular specificity and sensitivity, which enable the study of cell viability, cell deformation, cell-protein, cell-nanoparticle, cell-cell interaction, etc. In transfusion medicine, RTS can give valuable insights into the storage lesions and effects of various preservatives and intravenous fluids on blood cells. Summary: By analyzing the Raman spectra of individual blood cells, RTS can detect changes in the cellular blood components which can be used to monitor the quality of blood products during storage and transfusion. The present review article highlights the principle and clinical applications of RTS in transfusion medicine. Key Messages: Raman spectroscopy is a versatile analytical method for biomedical research. Combining the Raman spectroscopy method with the optical tweezers technique will allow us to explore the dynamics of live single cells in their physiological medium.
{"title":"Advancing Transfusion Medicine through Raman Tweezers Spectroscopy: A Review of Recent Progress and Future Perspectives","authors":"Mithun Nelliat, G. Mohan, J. Lukose, S. Shastry, S. Chidangil","doi":"10.1159/000538972","DOIUrl":"https://doi.org/10.1159/000538972","url":null,"abstract":"Background: Raman tweezers spectroscopy (RTS) is a powerful tool that combines optical tweezers and Raman spectroscopy to study single living cells. RTS has become increasingly popular in biomedical and clinical research due to its high molecular specificity and sensitivity, which enable the study of cell viability, cell deformation, cell-protein, cell-nanoparticle, cell-cell interaction, etc. In transfusion medicine, RTS can give valuable insights into the storage lesions and effects of various preservatives and intravenous fluids on blood cells. Summary: By analyzing the Raman spectra of individual blood cells, RTS can detect changes in the cellular blood components which can be used to monitor the quality of blood products during storage and transfusion. The present review article highlights the principle and clinical applications of RTS in transfusion medicine. Key Messages: Raman spectroscopy is a versatile analytical method for biomedical research. Combining the Raman spectroscopy method with the optical tweezers technique will allow us to explore the dynamics of live single cells in their physiological medium.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"333 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141386535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. Yucel, Dilek Yapar, Ece Vural, Nurcan Alhan, Sertac Vurgun, Unal Atas, M. Alemdar, Mustafa Karaca, U. Iltar, O. Salim, L. Undar
Background: To minimize adverse events of peripheral blood stem cell (PBSC) collection in healthy donors, it is reasonable to limit the total dose of granulocyte colony-stimulating factor (G-CSF) and/or the number of apheresis days without decreasing of PBSCs yield. Therefore, we have started to collect G-CSF induced PBSCs on day 4 instead of on day 5. So, we retrospectively aimed to investigate the results of this 4-day G-CSF administration. Study Design and Methods: Seventy-six healthy donors who performed on G-CSF induced PBSCs donation consecutively between January 2020 and July 2022 were included in this study. G-CSF (filgrastim) at 2 × 5 µg/kg/day subcutaneously was applied. Apheresis started on day 4. Results: Sixty-nine (90.8%) of 76 donors provided enough PBSCs on day 4 apheresis session. Younger age (p = 0.004), higher PB CD34+ cell count on the 4th day of G-CSF (p < 0.001), and male donor (p = 0.010) were correlated with increased amounts of PBSCs yield. Univariate and multivariate logistic regression analyses to predict very good mobilizers (collected PBSCs ≥8 × 106/kg after the first apheresis) were performed. In multivariate logistic regression analyses, male sex (p = 0.004), PB CD34+ cell count ≥100/µL on the 4th day of G-CSF (p < 0.001), and glomerular filtration rate ≥115 mL/min (p = 0.031) were found to be independent predicting factors to demonstrate very good mobilizer. Conclusion: It seems that starting the apheresis on the 4th day of G-CSF administration is effective and to provide minimal G-CSF exposure in healthy donors.
{"title":"Single Apheresis Session on the 4th Day of Granulocyte Colony-Stimulating Factor Administration Seems Convenient to Collect Enough Peripheral Blood Stem Cells from Healthy Donors","authors":"O. Yucel, Dilek Yapar, Ece Vural, Nurcan Alhan, Sertac Vurgun, Unal Atas, M. Alemdar, Mustafa Karaca, U. Iltar, O. Salim, L. Undar","doi":"10.1159/000538457","DOIUrl":"https://doi.org/10.1159/000538457","url":null,"abstract":"Background: To minimize adverse events of peripheral blood stem cell (PBSC) collection in healthy donors, it is reasonable to limit the total dose of granulocyte colony-stimulating factor (G-CSF) and/or the number of apheresis days without decreasing of PBSCs yield. Therefore, we have started to collect G-CSF induced PBSCs on day 4 instead of on day 5. So, we retrospectively aimed to investigate the results of this 4-day G-CSF administration. Study Design and Methods: Seventy-six healthy donors who performed on G-CSF induced PBSCs donation consecutively between January 2020 and July 2022 were included in this study. G-CSF (filgrastim) at 2 × 5 µg/kg/day subcutaneously was applied. Apheresis started on day 4. Results: Sixty-nine (90.8%) of 76 donors provided enough PBSCs on day 4 apheresis session. Younger age (p = 0.004), higher PB CD34+ cell count on the 4th day of G-CSF (p < 0.001), and male donor (p = 0.010) were correlated with increased amounts of PBSCs yield. Univariate and multivariate logistic regression analyses to predict very good mobilizers (collected PBSCs ≥8 × 106/kg after the first apheresis) were performed. In multivariate logistic regression analyses, male sex (p = 0.004), PB CD34+ cell count ≥100/µL on the 4th day of G-CSF (p < 0.001), and glomerular filtration rate ≥115 mL/min (p = 0.031) were found to be independent predicting factors to demonstrate very good mobilizer. Conclusion: It seems that starting the apheresis on the 4th day of G-CSF administration is effective and to provide minimal G-CSF exposure in healthy donors.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"9 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Kronstein-Wiedemann, Stephan R. Künzel, Jessica Thiel, Torsten Tonn
Background: MicroRNAs (miRNAs) are small, endogenous non-coding RNA molecules that inhibit gene expression through either destabilization of the target mRNA or translational repression. MiRNAs recognize target sites, most commonly found in the 3′-untranslated regions of cognate mRNAs. This review aims to provide a state-of-the-art overview of the role of miRNAs in the regulation of major blood group antigens such as ABH as well as cancer-specific glycans. Summary: Besides their known roles in the control of developmental processes, proliferation, apoptosis, and carcinogenesis, miRNAs have recently been identified to play a regulatory role during erythropoiesis and blood group antigen expression. Since only little is known about the function of the red cell membrane proteins carrying blood group antigens, it is of great interest to shed light on the regulatory mechanisms of blood group gene expression. Some carrier proteins of blood group antigens are not restricted to red blood cells and are widely expressed in other bodily fluids and tissues and quite a few play a crucial role in tumor cells, as either tumor suppressors or promoters. Key Message: All available data point at a tremendous physiological as well as pathophysiological relevance of miRNAs in context of blood group regulation. Furthermore, miRNAs are involved in the regulation of pleiotropic genetic pathways such as hematopoiesis and tumorigenesis and thus have to be studied in future research on this subject.
{"title":"Role of MiRNA in the Regulation of Blood Group Expression","authors":"R. Kronstein-Wiedemann, Stephan R. Künzel, Jessica Thiel, Torsten Tonn","doi":"10.1159/000538866","DOIUrl":"https://doi.org/10.1159/000538866","url":null,"abstract":"Background: MicroRNAs (miRNAs) are small, endogenous non-coding RNA molecules that inhibit gene expression through either destabilization of the target mRNA or translational repression. MiRNAs recognize target sites, most commonly found in the 3′-untranslated regions of cognate mRNAs. This review aims to provide a state-of-the-art overview of the role of miRNAs in the regulation of major blood group antigens such as ABH as well as cancer-specific glycans. Summary: Besides their known roles in the control of developmental processes, proliferation, apoptosis, and carcinogenesis, miRNAs have recently been identified to play a regulatory role during erythropoiesis and blood group antigen expression. Since only little is known about the function of the red cell membrane proteins carrying blood group antigens, it is of great interest to shed light on the regulatory mechanisms of blood group gene expression. Some carrier proteins of blood group antigens are not restricted to red blood cells and are widely expressed in other bodily fluids and tissues and quite a few play a crucial role in tumor cells, as either tumor suppressors or promoters. Key Message: All available data point at a tremendous physiological as well as pathophysiological relevance of miRNAs in context of blood group regulation. Furthermore, miRNAs are involved in the regulation of pleiotropic genetic pathways such as hematopoiesis and tumorigenesis and thus have to be studied in future research on this subject.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"7 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ilias Doxiadis, H. Loeffler-Wirth, Nils Lachmann, Claudia Lehmann
Background: HLA epitopes are currently in the focus of transplantation immunogenetics. The main reason is the complexity of the HLA system with >38,000 alleles, the number of which increases steadily. These alleles are determined by the current state-of-the art typing methods like second- and third-generation sequencing. Screening for HLA antibodies is hampered by the lack of specific target beads with all possible alleles described. Summary: A way to circumvent the problem is to define HLA epitopes. The number of antibody-confirmed epitopes, on the other hand, was found to be 72 for HLA class I and 74 for HLA class II. Here, we elaborate on the current knowledge on these HLA epitopes. Absolute definitions of these structures are not yet available. Key Messages: Making use of eplets is a comparable way allowing statistical analyses. However, one should keep in mind that the results obtained are approximative or perhaps better associative. Continuous collaboration is needed for the full understanding of the HLA epitopes. The reactivity toward epitopes remains patient-specific.
{"title":"A Short History of B-Cell HLA Epitopes","authors":"Ilias Doxiadis, H. Loeffler-Wirth, Nils Lachmann, Claudia Lehmann","doi":"10.1159/000538447","DOIUrl":"https://doi.org/10.1159/000538447","url":null,"abstract":"Background: HLA epitopes are currently in the focus of transplantation immunogenetics. The main reason is the complexity of the HLA system with >38,000 alleles, the number of which increases steadily. These alleles are determined by the current state-of-the art typing methods like second- and third-generation sequencing. Screening for HLA antibodies is hampered by the lack of specific target beads with all possible alleles described. Summary: A way to circumvent the problem is to define HLA epitopes. The number of antibody-confirmed epitopes, on the other hand, was found to be 72 for HLA class I and 74 for HLA class II. Here, we elaborate on the current knowledge on these HLA epitopes. Absolute definitions of these structures are not yet available. Key Messages: Making use of eplets is a comparable way allowing statistical analyses. However, one should keep in mind that the results obtained are approximative or perhaps better associative. Continuous collaboration is needed for the full understanding of the HLA epitopes. The reactivity toward epitopes remains patient-specific.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"39 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140673331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Schrezenmeier, Mira Choi, B. Globke, Thomas Dörner, Alexandra Leimbach, B. Osmanodja, Alexander Schramm, Kerstin Amann, K. Eckardt, K. Budde, Robert Öllinger, N. Lachmann, F. Halleck
Introduction: The transplantation of highly sensitized patients remains a major obstacle. Immunized patients wait longer for a transplant if not prioritized, and if transplanted, their transplant outcome is worse. Case Presentation: We report a successful AB0- and HLA-incompatible living donor kidney transplantation in a 35-year-old female patient with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The patient had a positive T- and B-cell complement-dependent cytotoxicity (CDC) crossmatch and previous graft loss due to renal vein thrombosis. We treated the patient with intravenous immunoglobulins, rituximab, horse anti-thymocyte globulin, daratumumab, and imlifidase, besides standard immunosuppression. All IgG antibodies were sensitive to imlifidase treatment. Besides donor-specific HLA antibodies, anti-dsDNA antibodies and antiphospholipid antibodies were cleaved. The patient initially had delayed graft function. Two kidney biopsies (day 7 and day 14) revealed acute tubular necrosis without signs of HLA antibody-mediated rejection. On posttransplant day 30, hemodialysis was stopped, and creatinine levels declined over the next weeks to a baseline creatinine of about 1.7 mg/dL after 12 months. Conclusion: In this case, a novel multimodal treatment strategy including daratumumab and imlifidase enabled successful kidney transplantation for a highly immunized patient with antiphospholipid antibodies.
{"title":"Successful Desensitization with Imlifidase and Daratumumab in a Highly Immunized, Crossmatch Positive, Blood Group-Incompatible Living-Donor Re-Transplant Recipient with Systemic Lupus Erythematosus and Antiphospholipid Syndrome","authors":"E. Schrezenmeier, Mira Choi, B. Globke, Thomas Dörner, Alexandra Leimbach, B. Osmanodja, Alexander Schramm, Kerstin Amann, K. Eckardt, K. Budde, Robert Öllinger, N. Lachmann, F. Halleck","doi":"10.1159/000538513","DOIUrl":"https://doi.org/10.1159/000538513","url":null,"abstract":"Introduction: The transplantation of highly sensitized patients remains a major obstacle. Immunized patients wait longer for a transplant if not prioritized, and if transplanted, their transplant outcome is worse. Case Presentation: We report a successful AB0- and HLA-incompatible living donor kidney transplantation in a 35-year-old female patient with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The patient had a positive T- and B-cell complement-dependent cytotoxicity (CDC) crossmatch and previous graft loss due to renal vein thrombosis. We treated the patient with intravenous immunoglobulins, rituximab, horse anti-thymocyte globulin, daratumumab, and imlifidase, besides standard immunosuppression. All IgG antibodies were sensitive to imlifidase treatment. Besides donor-specific HLA antibodies, anti-dsDNA antibodies and antiphospholipid antibodies were cleaved. The patient initially had delayed graft function. Two kidney biopsies (day 7 and day 14) revealed acute tubular necrosis without signs of HLA antibody-mediated rejection. On posttransplant day 30, hemodialysis was stopped, and creatinine levels declined over the next weeks to a baseline creatinine of about 1.7 mg/dL after 12 months. Conclusion: In this case, a novel multimodal treatment strategy including daratumumab and imlifidase enabled successful kidney transplantation for a highly immunized patient with antiphospholipid antibodies.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"123 33","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gerd Klinkmann, F. Doss, S. Doß, Antje Schwarz, Susanne Reichert, Daniel A. Reuter, K. Selleng, Thomas Thiele, Steffen Mitzner, J. Altrichter
Background: Granulocyte concentrates (GCs) are usually prepared by single-donor apheresis after G-CSF pretreatment and have to be transfused within 24 h after cell collection because of the rapid decrease in pH and cell survival due to high lactate production by red blood cell contamination. GCs pooled from buffy coats of whole blood donations could improve the availability of these products. Methods to reduce red blood cell and platelet contamination may improve storability. We developed a manufacturing process for pooled GCs and investigated cell viability and functionality over time. Methods: Six ABO blood group-identical buffy coats were pooled. Subsequently, the red blood cells spontaneously sedimented after the addition of hydroxyethyl starch. The resulting leukocyte-enriched supernatant was washed twice with saline to reduce platelets and was resuspended in ABO-identical donor plasma. The leukocyte concentrate was transferred to a platelet storage bag and stored up to 72 h at 20–24°C w/o agitation. Cell count and viability, pH, blood gases, phagocytosis, and oxidative burst activity were monitored. Results: The number of red blood cells and platelets was reduced to 0.4% and 6.1% of the baseline levels. About 50% of the original present leukocytes could be extracted (n = 76). In the course of 72 h of storage, there were no significant changes in white blood cell counts (p = 0.12). The viability exceeded 98% during the entire period. The rate of granulocytes performing phagocytosis and oxidative burst remained above 95% anytime. Conclusion: GCs prepared from pooled buffy coats provide a precious alternative to granulocytes obtained from apheresis. Reduction of red blood cells and platelets by more than 90% extends the maximum shelf life of GCs from 24 h to 72 h. For a therapeutic dose of at least 1 × 1010 granulocytes, 15–20 buffy coats are required.
{"title":"Purified Granulocyte Concentrates from Buffy Coats with Extended Storage Time","authors":"Gerd Klinkmann, F. Doss, S. Doß, Antje Schwarz, Susanne Reichert, Daniel A. Reuter, K. Selleng, Thomas Thiele, Steffen Mitzner, J. Altrichter","doi":"10.1159/000537698","DOIUrl":"https://doi.org/10.1159/000537698","url":null,"abstract":"Background: Granulocyte concentrates (GCs) are usually prepared by single-donor apheresis after G-CSF pretreatment and have to be transfused within 24 h after cell collection because of the rapid decrease in pH and cell survival due to high lactate production by red blood cell contamination. GCs pooled from buffy coats of whole blood donations could improve the availability of these products. Methods to reduce red blood cell and platelet contamination may improve storability. We developed a manufacturing process for pooled GCs and investigated cell viability and functionality over time. Methods: Six ABO blood group-identical buffy coats were pooled. Subsequently, the red blood cells spontaneously sedimented after the addition of hydroxyethyl starch. The resulting leukocyte-enriched supernatant was washed twice with saline to reduce platelets and was resuspended in ABO-identical donor plasma. The leukocyte concentrate was transferred to a platelet storage bag and stored up to 72 h at 20–24°C w/o agitation. Cell count and viability, pH, blood gases, phagocytosis, and oxidative burst activity were monitored. Results: The number of red blood cells and platelets was reduced to 0.4% and 6.1% of the baseline levels. About 50% of the original present leukocytes could be extracted (n = 76). In the course of 72 h of storage, there were no significant changes in white blood cell counts (p = 0.12). The viability exceeded 98% during the entire period. The rate of granulocytes performing phagocytosis and oxidative burst remained above 95% anytime. Conclusion: GCs prepared from pooled buffy coats provide a precious alternative to granulocytes obtained from apheresis. Reduction of red blood cells and platelets by more than 90% extends the maximum shelf life of GCs from 24 h to 72 h. For a therapeutic dose of at least 1 × 1010 granulocytes, 15–20 buffy coats are required.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"54 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140709799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Brixner, Marcia Cardoso, Erik Spaepen, Erhard Seifried
Introduction: In Germany, demand for platelet transfusion is maintained or even increasing, despite a decrease in whole blood donations observed in the last decade. The shelf-life of platelet concentrates (PCs) in Germany is 4 days, which can be extended to 5 days if appropriate safety measures are used. This short shelf-life leads to decreased PC availability. Methods: We investigated the impact of PC shelf-life extension on PC shortage, using a mathematical simulation model based on the PC production and delivery statistics of the Frankfurt Institute of the German Red Cross Transfusion Service of Baden-Württemberg-Hessen. We used a 2.2-year dataset for PC production and delivery as input data for a Monte Carlo inventory management simulation, focusing on PC shortage. The model generated the daily stock (expressed as mean number of PC units ± standard deviation), mean PC age at release, mean number of expired PC units, and shortage rates (i.e., requiring the release of more PCs than available), overall and by PC blood group. Results: Over 2.2 years, a total of 74,322 PC units were produced and 62,178 units were released at the Frankfurt Institute; the overall overproduction rate was 19.5%. Shortage rates decrease with an increase in PC shelf-life and/or increase in overproduction rates. At an overproduction rate of 20%, shortage rates would be reduced from 2.8% for a 4-day shelf-life to 0.7%, 0.3%, and 0.2%, for shelf-life lengths of 5, 6, and 7 days, respectively. Extending the PC shelf-life to 6 or 7 days would eliminate shortages almost entirely, including for rare bloods. Conclusion: These results can inform blood services and regulatory authorities on the potential medical and economic impact of extending PC shelf-life to 6 or 7 days.
导言：在德国，尽管全血献血量在过去十年中有所下降，但对血小板输血的需求却保持甚至有所增加。在德国，血小板浓缩物（PCs）的保质期为 4 天，如果采取适当的安全措施，保质期可延长至 5 天。较短的保质期导致血小板浓缩物的可用性降低。方法：我们根据德国巴登-符腾堡-黑森州红十字输血服务中心法兰克福研究所的 PC 生产和交付统计数据，使用数学模拟模型研究了延长 PC 保质期对 PC 短缺的影响。我们将 2.2 年的 PC 生产和交付数据集作为蒙特卡罗库存管理模拟的输入数据，重点关注 PC 短缺问题。该模型按 PC 血型生成了日库存量（以 PC 单位平均值±标准差表示）、出库时的 PC 平均年龄、过期 PC 单位平均值和短缺率（即需要出库的 PC 数量多于可用数量）。结果：在 2.2 年的时间里，法兰克福研究所共生产了 74,322 个 PC 单位，发放了 62,178 个 PC 单位；总体超产率为 19.5%。随着个人电脑保质期的延长和/或超额生产率的提高，短缺率也随之降低。超产率为 20%时，保质期为 4 天的短缺率为 2.8%，保质期为 5 天、6 天和 7 天的短缺率分别为 0.7%、0.3% 和 0.2%。将 PC 保存期延长至 6 天或 7 天几乎可以完全消除短缺现象，包括稀有血液的短缺。结论这些结果可以让血液服务机构和监管机构了解将 PC 保存期延长至 6 或 7 天可能带来的医疗和经济影响。
{"title":"Impact of Shelf-Life Extension on Platelet Availability: Results from an Inventory Management Modeling Study","authors":"V. Brixner, Marcia Cardoso, Erik Spaepen, Erhard Seifried","doi":"10.1159/000537700","DOIUrl":"https://doi.org/10.1159/000537700","url":null,"abstract":"Introduction: In Germany, demand for platelet transfusion is maintained or even increasing, despite a decrease in whole blood donations observed in the last decade. The shelf-life of platelet concentrates (PCs) in Germany is 4 days, which can be extended to 5 days if appropriate safety measures are used. This short shelf-life leads to decreased PC availability. Methods: We investigated the impact of PC shelf-life extension on PC shortage, using a mathematical simulation model based on the PC production and delivery statistics of the Frankfurt Institute of the German Red Cross Transfusion Service of Baden-Württemberg-Hessen. We used a 2.2-year dataset for PC production and delivery as input data for a Monte Carlo inventory management simulation, focusing on PC shortage. The model generated the daily stock (expressed as mean number of PC units ± standard deviation), mean PC age at release, mean number of expired PC units, and shortage rates (i.e., requiring the release of more PCs than available), overall and by PC blood group. Results: Over 2.2 years, a total of 74,322 PC units were produced and 62,178 units were released at the Frankfurt Institute; the overall overproduction rate was 19.5%. Shortage rates decrease with an increase in PC shelf-life and/or increase in overproduction rates. At an overproduction rate of 20%, shortage rates would be reduced from 2.8% for a 4-day shelf-life to 0.7%, 0.3%, and 0.2%, for shelf-life lengths of 5, 6, and 7 days, respectively. Extending the PC shelf-life to 6 or 7 days would eliminate shortages almost entirely, including for rare bloods. Conclusion: These results can inform blood services and regulatory authorities on the potential medical and economic impact of extending PC shelf-life to 6 or 7 days.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"54 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140752336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Peereboom, Anna E. Maranus, Laura M. Timmerman, K. Geneugelijk, Eric Spierings
Introduction: Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the development of graft-versus-host disease (GvHD). The number of CD8+ T-cell epitopes available for indirect allorecognition as predicted by the PIRCHE algorithm has been shown to be associated with GvHD development. As a proof of principle, PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro and in vivo. Methods: PIRCHE-I analysis was performed to identify HLA-DPB1-derived peptides that could theoretically bind to HLA-A*02:01. PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro by investigating binding affinities of HLA-DPB1-derived peptides to the HLA-A*02:01 in a competition-based binding assay. To investigate the capacity of HLA-DPB1-derived peptides to elicit a T-cell response in vivo, mice were immunized with these peptides. T-cell alloreactivity was subsequently evaluated using an interferon-gamma ELISpot assay. Results: The PIRCHE-I algorithm identified five HLA-DPB1-derived peptides (RMCRHNYEL, YIYNREEFV, YIYNREELV, YIYNREEYA, and YIYNRQEYA) to be presented by HLA-A*02:01. Binding of these peptides to HLA-A*02:01 was confirmed in a competition-based peptide binding assay, all showing an IC50 value of 21 μm or lower. The peptides elicited an interferon-gamma response in vivo. Conclusion: Our results indicate that the PIRCHE-I algorithm can identify potential immunogenic HLA-DPB1-derived peptides present in recipients of an HLA-DPB1-mismatched donor. These combined in vitro and in vivo observations strengthen the validity of the PIRCHE-I algorithm to identify HLA-DPB1 mismatch-related GvHD development upon HSCT.
{"title":"Experimental Data on PIRCHE and T-Cell Reactivity: HLA-DPB1-Derived Peptides Identified by PIRCHE-I Show Binding to HLA-A*02:01 in vitro and T-Cell Activation in vivo","authors":"E. Peereboom, Anna E. Maranus, Laura M. Timmerman, K. Geneugelijk, Eric Spierings","doi":"10.1159/000537789","DOIUrl":"https://doi.org/10.1159/000537789","url":null,"abstract":"Introduction: Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the development of graft-versus-host disease (GvHD). The number of CD8+ T-cell epitopes available for indirect allorecognition as predicted by the PIRCHE algorithm has been shown to be associated with GvHD development. As a proof of principle, PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro and in vivo. Methods: PIRCHE-I analysis was performed to identify HLA-DPB1-derived peptides that could theoretically bind to HLA-A*02:01. PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro by investigating binding affinities of HLA-DPB1-derived peptides to the HLA-A*02:01 in a competition-based binding assay. To investigate the capacity of HLA-DPB1-derived peptides to elicit a T-cell response in vivo, mice were immunized with these peptides. T-cell alloreactivity was subsequently evaluated using an interferon-gamma ELISpot assay. Results: The PIRCHE-I algorithm identified five HLA-DPB1-derived peptides (RMCRHNYEL, YIYNREEFV, YIYNREELV, YIYNREEYA, and YIYNRQEYA) to be presented by HLA-A*02:01. Binding of these peptides to HLA-A*02:01 was confirmed in a competition-based peptide binding assay, all showing an IC50 value of 21 μm or lower. The peptides elicited an interferon-gamma response in vivo. Conclusion: Our results indicate that the PIRCHE-I algorithm can identify potential immunogenic HLA-DPB1-derived peptides present in recipients of an HLA-DPB1-mismatched donor. These combined in vitro and in vivo observations strengthen the validity of the PIRCHE-I algorithm to identify HLA-DPB1 mismatch-related GvHD development upon HSCT.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"23 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140753810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filippo Frioni, E. Metafuni, M. A. Limongiello, N. Piccirillo, Giuseppina Massini, Claudio Pellegrino, S. Giammarco, F. Sorà, F. Autore, Luciana Teofili, Simona Sica, Patrizia Chiusolo
Introduction: Autoimmune hemolytic anemia (AIHA) occurs in 0.7–5.6% of patients undergoing hematopoietic stem cell transplantation, especially from unrelated or haploidentical donor or after lympho-depleted transplant; the majority of cases are represented by warm AIHA, occurring in a full donor chimerism setting. Standard treatments (corticosteroids, intravenous immunoglobulin, splenectomy, rituximab, cyclophosphamide, plasma exchange) lead to lower response rates than those reported in primary AIHA. Daratumumab use has been proposed in many autoimmune conditions (immune thrombocytopenic purpura, aplastic anemia, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, multiple sclerosis), but only few reports have been published on its use for post-HSCT AIHA, mainly in pediatric patients. Case Presentation: We report the successful use of daratumumab in a 68-year-old patient, suffering from post-HSCT AIHA. Five months after Rh-mismatched HSCT, the patient was diagnosed with anti-D AIHA. After first-line treatment (oral prednisone, rituximab, and plasma exchange) failure, being still transfusion-dependent with symptomatic anemia, he underwent treatment with daratumumab, achieving both clinical and laboratory responses. Discussion: Daratumumab may represent a safe and effective alternative to conventional immunosuppressive therapy, and it deserves further investigations.
{"title":"Posttransplant Autoimmune Hemolytic Anemia with Anti-D Specificity Successfully Treated with Daratumumab: A Case Report","authors":"Filippo Frioni, E. Metafuni, M. A. Limongiello, N. Piccirillo, Giuseppina Massini, Claudio Pellegrino, S. Giammarco, F. Sorà, F. Autore, Luciana Teofili, Simona Sica, Patrizia Chiusolo","doi":"10.1159/000535927","DOIUrl":"https://doi.org/10.1159/000535927","url":null,"abstract":"Introduction: Autoimmune hemolytic anemia (AIHA) occurs in 0.7–5.6% of patients undergoing hematopoietic stem cell transplantation, especially from unrelated or haploidentical donor or after lympho-depleted transplant; the majority of cases are represented by warm AIHA, occurring in a full donor chimerism setting. Standard treatments (corticosteroids, intravenous immunoglobulin, splenectomy, rituximab, cyclophosphamide, plasma exchange) lead to lower response rates than those reported in primary AIHA. Daratumumab use has been proposed in many autoimmune conditions (immune thrombocytopenic purpura, aplastic anemia, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, multiple sclerosis), but only few reports have been published on its use for post-HSCT AIHA, mainly in pediatric patients. Case Presentation: We report the successful use of daratumumab in a 68-year-old patient, suffering from post-HSCT AIHA. Five months after Rh-mismatched HSCT, the patient was diagnosed with anti-D AIHA. After first-line treatment (oral prednisone, rituximab, and plasma exchange) failure, being still transfusion-dependent with symptomatic anemia, he underwent treatment with daratumumab, achieving both clinical and laboratory responses. Discussion: Daratumumab may represent a safe and effective alternative to conventional immunosuppressive therapy, and it deserves further investigations.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"8 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140230842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amir Muhammad, Xueling Hu, Juan Pan, Weisheng Peng, Xia Li, Mingxia Huang, Zengyuan Luo, Dayang Jiang, Jin-biao Chen, Rong Tang, Xiangcheng Xiao
Introduction: Protein A immunoadsorption (IA) is proving to be an effective treatment method for autoimmune diseases and other disorders. Regional citrate anticoagulation (RCA) prevents clotting in extracorporeal circuits without increasing hemorrhage risk in high bleeding risk patients, but there are no specific guidelines for its application in IA. We aimed to evaluate the safety and adverse effects of RCA used in IA therapy. Methods: We conducted a retrospective cohort study of forty-five RCA-IA sessions in 14 HLA-incompatible kidney transplant recipients with focus on the safety and adverse effects of RCA in IA. The extracorporeal circuit was equipped with 4% trisodium citrate solution as an anticoagulant and 10% calcium gluconate solution to compensate for calcium loss. The adverse events, including coagulation and blood biochemical indexes, especially calcium level, were recorded. Results: Our study found that 93.33% of the sessions were without circuit clotting or other significant complications. A slight decrease in fibrinogen level was observed, but without significant variations in other coagulation indexes or platelet count. There was a slight elevation in the potential of hydrogen, bicarbonate, and base excess after 2 h and 6 h posttreatment relative to prior treatment, but these returned to normal levels within 24 h posttreatment. Conclusion: RCA is a feasible, effective, and safe anticoagulation option for IA treatment in HLA-incompatible kidney transplant recipients. Electrolyte disturbances, especially alkalosis, hypocalcemia, hypomagnesemia, and fluid status, should be closely monitored and managed.
{"title":"The Application of Regional Citrate Anticoagulation in Protein A Immunoadsorption: A Single-Center Retrospective Cohort Study","authors":"Amir Muhammad, Xueling Hu, Juan Pan, Weisheng Peng, Xia Li, Mingxia Huang, Zengyuan Luo, Dayang Jiang, Jin-biao Chen, Rong Tang, Xiangcheng Xiao","doi":"10.1159/000536544","DOIUrl":"https://doi.org/10.1159/000536544","url":null,"abstract":"Introduction: Protein A immunoadsorption (IA) is proving to be an effective treatment method for autoimmune diseases and other disorders. Regional citrate anticoagulation (RCA) prevents clotting in extracorporeal circuits without increasing hemorrhage risk in high bleeding risk patients, but there are no specific guidelines for its application in IA. We aimed to evaluate the safety and adverse effects of RCA used in IA therapy. Methods: We conducted a retrospective cohort study of forty-five RCA-IA sessions in 14 HLA-incompatible kidney transplant recipients with focus on the safety and adverse effects of RCA in IA. The extracorporeal circuit was equipped with 4% trisodium citrate solution as an anticoagulant and 10% calcium gluconate solution to compensate for calcium loss. The adverse events, including coagulation and blood biochemical indexes, especially calcium level, were recorded. Results: Our study found that 93.33% of the sessions were without circuit clotting or other significant complications. A slight decrease in fibrinogen level was observed, but without significant variations in other coagulation indexes or platelet count. There was a slight elevation in the potential of hydrogen, bicarbonate, and base excess after 2 h and 6 h posttreatment relative to prior treatment, but these returned to normal levels within 24 h posttreatment. Conclusion: RCA is a feasible, effective, and safe anticoagulation option for IA treatment in HLA-incompatible kidney transplant recipients. Electrolyte disturbances, especially alkalosis, hypocalcemia, hypomagnesemia, and fluid status, should be closely monitored and managed.","PeriodicalId":505859,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"4 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140241416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：