Jessie A. Swanson, M. Soland, Scott A. Hammel, J. Juskewitch
{"title":"Effect of Water Bath versus Refrigerator Thaw on Cryoprecipitate Fibrinogen and Factor VIII Content Using a Pre-Pooled Plasma Experimental Approach","authors":"Jessie A. Swanson, M. Soland, Scott A. Hammel, J. Juskewitch","doi":"10.1159/000540089","DOIUrl":"https://doi.org/10.1159/000540089","url":null,"abstract":"Introduction: Originally developed as a form of factor VIII concentrate, cryoprecipitate’s primary clinical use has changed to treat fibrinogen deficiency as highlighted by recent approval of pathogen-reduced cryoprecipitated fibrinogen concentrates. The methodology by which frozen plasma is thawed during cryoprecipitate manufacturing is not standardized. This study compared plasma thawing techniques on cryoprecipitate fibrinogen and factor VIII levels. Methods: A matched pairwise experimental design was employed across three experiments to compare plasma thawing approaches (water bath or 24–48 h refrigerator). Each experiment involved the creation of 10 sets of ten homogenous frozen plasma pools which were then used to manufacture 10 pairs of cryoprecipitate pools differing only by assigned plasma thawing method. Total cryoprecipitate fibrinogen and factor VIII content between plasma thawing methods were compared using matched t-testing within each experiment. Results: Compared to water bath thawing, 24-h refrigerator thawing led to significantly higher cryoprecipitate fibrinogen content (2,554 mg vs. 1,824 mg; p < 0.001) and significantly lower cryoprecipitate factor VIII content (601 IU vs. 709 IU; p < 0.001). Longer refrigerator thaw times (36 and 48 h) led to significantly higher cryoprecipitate fibrinogen content than 24-h refrigerator thaw (3,180 mg vs. 2,956 mg and 2,893 mg vs. 2,483 mg, respectively; p = 0.01–0.03). Conclusion: Using homogenous frozen plasma units in a matched pairwise experimental design, refrigerator plasma thawing led to superior cryoprecipitate fibrinogen yields and inferior cryoprecipitate factor VIII yields. When maximizing cryoprecipitate fibrinogen yields, refrigerator plasma thawing, and in particular longer thawing times (36–48 h), should be considered.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141819635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Novel c.459_460insC Variation in the XK Gene Associated with McLeod Syndrome","authors":"Bing Zhang, Shifang Yu, Xiaozhen Hong, Xianguo Xu, Faming Zhu","doi":"10.1159/000539875","DOIUrl":"https://doi.org/10.1159/000539875","url":null,"abstract":"Introduction: McLeod syndrome (MLS) is a rare X-linked recessive disorder affecting multiple systems. Herein, we present the clinical symptoms, laboratory diagnostic results, and genetic characteristics of a patient with MLS caused by a novel c.459_460insC variation in the XK gene. Case Presentation: A 58-year-old male Chinese patient presented with neurological symptoms, seeking belated medical attention at the hospital. Numerous laboratory tests indicated a high likelihood of MLS, featuring chronic granulomatosis and neuroacanthocytosis. The patient’s blood samples were sent to the Blood Center of Zhejiang Province, China, for further analysis. Sequencing analysis revealed a novel hemizygous c.459_460insC variation in exon 2 of the XK gene. Therefore, we identified a patient with MLS possessing a novel genetic variation (GenBank Accession No. OQ473658). Conclusion: Our findings elucidate a novel c.459_460insC variation associated with MLS, resulting in a frameshift and premature stop codon (p.Leu154Profs*45). The clinical manifestations, laboratory examination, and XK gene analysis in this case will aid in diagnosing MLS in future patients.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141833419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Uzun, J. Lucic, I. Marini, F. Rigoni, Franziska Lyshy, Omid Haghighi, N. Wolska, S. Nowak-Harnau, K. Althaus, Ulrich J. Sachs, T. Bakchoul
{"title":"In vitro Generated Megakaryocytes for the Detection of Human Platelet Antigen-Specific Alloantibodies","authors":"G. Uzun, J. Lucic, I. Marini, F. Rigoni, Franziska Lyshy, Omid Haghighi, N. Wolska, S. Nowak-Harnau, K. Althaus, Ulrich J. Sachs, T. Bakchoul","doi":"10.1159/000539617","DOIUrl":"https://doi.org/10.1159/000539617","url":null,"abstract":"Introduction: Serologic characterization of antihuman platelet antigen (HPA) alloantibodies is crucial in fetal neonatal alloimmune thrombocytopenia. The gold standard MAIPA assay requires fresh platelets from HPA-genotyped donors, which is challenging for some laboratories. Megakaryocytes express HPA epitopes and offer an alternative source for detecting anti-HPA antibodies. The objective of this study was to assess the efficacy of a novel assay called monoclonal antibody immobilization of megakaryocyte antigens (MAIMA) for detecting anti-HPA antibodies. Methods: CD34+ cells from buffy coats were differentiated into megakaryocytes in vitro. The performance of the MAIMA assay was evaluated using WHO reference reagents for HPA-1a, HPA-3a, and HPA-5b, along with sera samples from patients who had well-characterized anti-HPA antibodies. Results: The WHO anti-HPA-1a reference reagent showed similar binding to megakaryocytes and platelets in MAIMA and MAIPA, respectively. On the other hand, optical density (OD) values for the WHO anti-HPA-3a reference reagent were lower in MAIMA than in MAIPA. Anti-HPA-5b antibodies were not detectable in MAIMA. Patients’ sera containing anti-HPA-1a antibodies were successfully detected in MAIMA in all clinical samples. Moreover, OD values in MAIPA and MAIMA showed high correlation (r = 0.96, p < 0.001). MAIMA was reactive for samples with anti-HPA-3a as well as anti-HPA-3b; however, OD values were lower compared to MAIPA. Interestingly, all patient samples with anti-HPA-5b antibodies were tested negative in MAIMA. Conclusion: In vitro generated megakaryocytes can be used to detect anti-HPA-1a alloantibodies. However, despite this potential, they may be less suitable for the detection of alloantibodies against other HPAs such as HPA-5b.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141833431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effectors of the Future: Universal Chimeric Antigen Receptor","authors":"Lara Sophie Schlegel, Patrick Schlegel","doi":"10.1159/000539609","DOIUrl":"https://doi.org/10.1159/000539609","url":null,"abstract":"Background: Cellular therapies leveraging genetically engineered immune effector cells have witnessed a remarkable surge in success, particularly evident in the notable high rates of remission induction and durable remissions observed in a substantial proportion of heavily pretreated patients with refractory B-lineage malignancies. A diverse array of effector cells and therapeutic strategies are now at our disposal, representing the culmination of advancements made over the past 3 decades. The swift pace of development in modern genetic diagnostics, the emergence of spatial proteomics, and the expanding capabilities and precision of computational sciences have profoundly enriched our comprehension of tumor biology and the intricate workings of our immune system. Empowered by advancements in synthetic biology and genome editing, we can expedite the development of next-generation immune effector cells tailored for clinical applications, balancing safety with efficacy. Summary: Universal adapter chimeric antigen receptor (CAR) technologies present the most straightforward solution to tackle antigen heterogeneity and antigen evasion mechanisms employed by tumors. Moreover, due to the decoupling of antigen recognition and signaling in adapter CAR technologies, additional effector functions can safely enhance anticancer activity and most importantly, synergistic combination of patient-specific cellular products with off-the-shelf manufactured antibodies promise increased cost-efficiency. The pivotal collaboration between clinical trial units and regulatory institutions holds the key to surmounting contemporary challenges in trial design, potentially paving the way for the exploration of patient-individualized therapies. Key Messages: In this review, we elaborate on the concept of antibody-dependent cellular cytotoxicity mediated by universal adapter CARs and delineate how recent strides in CAR engineering have the potential to furnish a versatile cellular platform, ushering in an era of cancer-adapted, multitargeted immunotherapies employing universal CAR effector cells.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141833526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of Blood Group Expression: Another Layer of Complexity to Consider.","authors":"Christoph Gassner, Martin L Olsson","doi":"10.1159/000539611","DOIUrl":"10.1159/000539611","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin Wipplinger, Sylvia Mink, Maike Bublitz, Christoph Gassner
{"title":"Regulation of the Lewis Blood Group Antigen Expression: A Literature Review Supplemented with Computational Analysis.","authors":"Martin Wipplinger, Sylvia Mink, Maike Bublitz, Christoph Gassner","doi":"10.1159/000538863","DOIUrl":"10.1159/000538863","url":null,"abstract":"<p><strong>Background: </strong>The Lewis (Le) blood group system, unlike most other blood groups, is not defined by antigens produced internally to the erythrocytes and their precursors but rather by glycan antigens adsorbed on to the erythrocyte membrane from the plasma. These oligosaccharides are synthesized by the two fucosyltransferases <i>FUT2</i> and <i>FUT3</i> mainly in epithelial cells of the digestive tract and transferred to the plasma. At their place of synthesis, some Lewis blood group carbohydrate antigen variants also seem to be involved in various gastrointestinal malignancies. However, relatively little is known about the transcriptional regulation of <i>FUT2</i> and <i>FUT3</i>.</p><p><strong>Summary: </strong>To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for <i>FUT2</i> and <i>FUT3</i> and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase <i>FUT2</i> and <i>FUT3</i> transcription and translation upon interaction.</p><p><strong>Key messages: </strong>Understanding the regulation of <i>FUT2</i> and <i>FUT3</i> is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HLA in Transplantation: Challenges and Perspectives.","authors":"Nils Lachmann, Axel Pruß","doi":"10.1159/000538982","DOIUrl":"10.1159/000538982","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eunike C. McGowan, Ping Chun Wu, Å. Hellberg, G. Lopez, Catherine A. Hyland, Martin L Olsson
{"title":"A Bioinformatically Initiated Approach to Evaluate GATA1 Regulatory Regions in Samples with Weak D, Del, or D– Phenotypes Despite Normal RHD Exons","authors":"Eunike C. McGowan, Ping Chun Wu, Å. Hellberg, G. Lopez, Catherine A. Hyland, Martin L Olsson","doi":"10.1159/000538469","DOIUrl":"https://doi.org/10.1159/000538469","url":null,"abstract":"Introduction: With over 360 blood group antigens in systems recognized, there are antigens, such as RhD, which demonstrate a quantitative reduction in antigen expression due to nucleotide variants in the non-coding region of the gene that result in aberrant splicing or a regulatory mechanism. This study aimed to evaluate bioinformatically predicted GATA1-binding regulatory motifs in the RHD gene for samples presenting with weak or apparently negative RhD antigen expression but showing normal RHD exons. Methods: Publicly available open chromatin region data were overlayed with GATA1 motif candidates in RHD. Genomic DNA from weak D, Del or D– samples with normal RHD exons (n = 13) was used to confirm RHD zygosity by quantitative PCR. Then, RHD promoter, intron 1, and intron 2 regions were amplified for Sanger sequencing to detect potential disruptions in the GATA1 motif candidates. Electrophoretic mobility shift assay (EMSA) was performed to assess GATA1-binding. Luciferase assays were used to assess transcriptional activity. Results: Bioinformatic analysis identified five of six GATA1 motif candidates in the promoter, intron 1 and intron 2 for investigation in the samples. Luciferase assays showed an enhancement in transcription for GATA1 motifs in intron 1 and for intron 2 only when the R2 haplotype variant (rs675072G>A) was present. GATA1 motifs were intact in 12 of 13 samples. For one sample with a Del phenotype, a novel RHD c.1–110A>C variant disrupted the GATA1 motif in the promoter which was supported by a lack of a GATA1 supershift in the EMSA and 73% transcriptional activity in the luciferase assay. Two samples were D+/D– chimeras. Conclusion: The bioinformatic predictions enabled the identification of a novel DEL allele, RHD c.1–110A>C, which disrupted the GATA1 motif in the proximal promoter. Although the majority of the samples investigated here remain unexplained, we provide GATA1 targets which may benefit future RHD regulatory investigations.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Britt Van Aelst, Karen Bens, B. Sabot, Sarah Vertongen, H. Feys, V. Compernolle, Katrijn R. Six
{"title":"Platelet Additive Solutions SSP+ and T-PAS+ Are Interchangeable for Platelet Concentrate Storage despite Differences in Composition and Plasticizer","authors":"Britt Van Aelst, Karen Bens, B. Sabot, Sarah Vertongen, H. Feys, V. Compernolle, Katrijn R. Six","doi":"10.1159/000538003","DOIUrl":"https://doi.org/10.1159/000538003","url":null,"abstract":"Introduction: Platelet additive solutions support ex vivo storage of platelet concentrates used for transfusion. The composition of platelet additive solutions within one generation (i.e., PAS-E) is similar but not identical. Additionally, the platelet additive solution storage bag may contain different plasticizers. This study compares the effect of two PAS-E solutions (SSP+ vs. T-PAS+, stored in a DEHP-containing and DEHP-free bag, respectively) to investigate if both additive solutions are interchangeable for platelet concentrate storage. Methods: Platelet concentrates stored in plasma supplemented with SSP+ or T-PAS+ were compared by using a pool-and-split design. Platelet metabolism was investigated using a blood gas analyzer. The degree of platelet storage lesion was determined by flow cytometry to measure granule release and phosphatidylserine scrambling. Results: The quality of platelet concentrates stored in either SSP+ or T-PAS+ is acceptable as pH decreased only slightly as a function of time. PH remained above 7.2 on exiration day +1 (day 6), which is far above the minimal criterion of 6.4. Platelet storage lesion was comparable between the two study groups with only limited α-granule release and phosphatidylserine surface expression in both groups after storage for 5 days, p = 0.547 and p = 0.825, respectively. Conclusion: This study supports a safe switch between SSP+ and T-PAS+ storage solutions for platelet concentrates despite slight differences in storage solution composition and DEHP content.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140380625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum.","authors":"","doi":"10.1159/000534302","DOIUrl":"https://doi.org/10.1159/000534302","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000533624.].</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}