Manal Monir Mansour, Mai El-Sayad Abd El-Hamid, Amal M. Dawoud, Sara A. El Derbaly, Mahmoud M. Mansour, Yasmin A.H.S. Younis
{"title":"Assessment of CTLA-4, LAG-3, and TIM-3 Expression in Pediatric Patients With β-Thalassemia Major and Their Association With Alloimmunization","authors":"Manal Monir Mansour, Mai El-Sayad Abd El-Hamid, Amal M. Dawoud, Sara A. El Derbaly, Mahmoud M. Mansour, Yasmin A.H.S. Younis","doi":"10.1016/j.tmrv.2026.151008","DOIUrl":"10.1016/j.tmrv.2026.151008","url":null,"abstract":"<div><div>β-thalassemia major induces chronic immune dysregulation driven by persistent anemia, iron overload, and repeated blood transfusions. It is associated with a complex and dynamic reshaping of immune homeostasis. In this context, immune checkpoints, CTLA-4, LAG-3, and TIM-3, have emerged as critical regulators of the balance between immune activation and tolerance. This study aimed to evaluate their expression and association with alloantibody formation. Pediatric β-thalassemia major patients on regular transfusions, including 22 alloimmunized and 22 nonalloimmunized, along with 22 healthy controls, were recruited for this study. Expression of CTLA-4, LAG-3, and TIM-3 was analyzed using reverse transcription PCR. TIM-3 expression was lower in patients than in controls (<em>P</em> = .003). This reduction was particularly evident in alloimmunized patients compared with the nonalloimmunized group (<em>P</em> = .001). Using random forest machine learning, cross-validated variable importance identified TIM-3 and CTLA-4 as important variables in the alloimmunization process. The pooled receiver operating characteristic (ROC) curve for the 3 studied markers in the patient groups demonstrated good discriminative performance between alloimmunized and non alloimmunized patients, with an area under the curve of 0.779, specificity 90.9%, and sensitivity 68.2%, outperforming conventional statistical analysis. In conclusion, downregulation of TIM-3 and CTLA-4 in pediatric β-thalassemia major patients may contribute to alloantibody formation.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 3","pages":"Article 151008"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and Safety of Pegfilgrastim for Hemopoietic Stem Cell Mobilization in Healthy Donors: A Systematic Review and Meta-Analysis","authors":"Aymane Bennani, El Khalil Benmansour, Ikram Sadki, Zahida Aqodad, Samia Sabri, Houda Bachir, Siham Hamaz, Habiba Alaoui Bennesser, Khalid Serraj","doi":"10.1016/j.tmrv.2026.151018","DOIUrl":"10.1016/j.tmrv.2026.151018","url":null,"abstract":"<div><div>Our study aims to determine the efficacy and the safety of pegfilgrastim for hematopoietic stem cell mobilization in healthy donors undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). PubMed, Scopus and CENTRAL (Cochrane Central Register of Controlled Trials) databases were systematically searched for eligible studies. Meta-analysis of proportions (for dichotomous outcomes) and meta-analysis of single means (for continuous data) were performed using a random-effects model. Heterogeneity was assessed using I2 statistics. A subgroup and leave-one-out sensitivity analyses were also conducted. The ROBINS-I tool was used for risk of bias assessment. R software (version 4.4.2) was used for all statistical analyses. PROSPERO registry number CRD420251015182. Seven studies were included. Following a single pegfilgrastim administration, 67% of donors achieved the target mobilization threshold of ≥4 × 10⁶ CD34⁺ cells/kg in one apheresis session (95% CI: 47%-85%). In the 12 mg subgroup, mobilization success increased to 76% (95% CI: 70%-81%). Circulating CD34+ progenitors reached a mean peak of 72.04/µL (95% CI: 50.69-102.37), increasing to 83.30/µL (95% CI: 73.11-94.91) with 12 mg dosing. The grafts yielded a mean of 6.75 × 10^6 CD34+ cells/kg recipient weight (95% CI: 5.12-8.89), rising to 7.95 × 10^6 CD34+ cells/kg (95% CI: 6.10-10.36) in the 12 mg dosing. Bone pain (76%; 95% CI: 51%-97%) and headaches (37%; 95% CI: 23%-53%) were the most reported side effects. Pegfilgrastim demonstrates favorable efficacy and tolerability for stem cell mobilization in healthy donors undergoing allo-HSCT. The 12 mg dose appears to be the most appropriate dose for achieving optimal mobilization outcomes.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 3","pages":"Article 151018"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alicia Valentin, Anita C. Windhorst, Ulrich J. Sachs, Sandra Wienzek-Lischka, Ivonne Bedei, Aline Wolter, Roland Axt-Fliedner
{"title":"Noninvasive Fetal HPA Genotyping for FNAIT: Diagnostic Accuracy and Technical Performance of Molecular Methods","authors":"Alicia Valentin, Anita C. Windhorst, Ulrich J. Sachs, Sandra Wienzek-Lischka, Ivonne Bedei, Aline Wolter, Roland Axt-Fliedner","doi":"10.1016/j.tmrv.2026.151017","DOIUrl":"10.1016/j.tmrv.2026.151017","url":null,"abstract":"<div><div>Noninvasive fetal human platelet antigen (HPA) genotyping has emerged as a promising tool for diagnosing fetal and neonatal alloimmune thrombocytopenia (FNAIT). Detection of fetal HPA incompatibility using cell-free fetal DNA from maternal blood allows for early, risk-adapted clinical assessment. This review evaluates the diagnostic accuracy, technical performance, and clinical applicability of noninvasive fetal HPA genotyping methods, including real-time polymerase chain reaction (PCR), allele-specific quantitative PCR, high-resolution melting PCR, droplet digital PCR (ddPCR), and next-generation sequencing (NGS). Across the analyzed studies, conventional PCR-based methods demonstrated reliable diagnostic performance for targeted HPA systems, particularly HPA-1, with consistent results at later gestational ages and suitability for routine molecular diagnostic laboratories. More advanced approaches, such as ddPCR and NGS, enabled accurate, multiplex fetal HPA genotyping across multiple antigen systems, including rarer HPA types, while also exhibiting robust performance at earlier gestational ages and lower fetal DNA fractions. These findings suggest that the choice of method is primarily determined by clinical context, required antigen coverage, and available laboratory infrastructure, with potential implications for risk stratification and clinical decision-making in pregnancies at risk for FNAIT.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 3","pages":"Article 151017"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victoria Ivankovic, Alicia Schulz, Nardin Farag, Risa Shorr, Daniel I. McIsaac, Dean A. Fergusson, Guillaume Martel
{"title":"Evaluating the Safety of Tranexamic Acid in Cancer Surgery: Clinical Evidence and Biological Rationale","authors":"Victoria Ivankovic, Alicia Schulz, Nardin Farag, Risa Shorr, Daniel I. McIsaac, Dean A. Fergusson, Guillaume Martel","doi":"10.1016/j.tmrv.2026.151009","DOIUrl":"10.1016/j.tmrv.2026.151009","url":null,"abstract":"<div><ul><li><span>•</span><span><div>TXA may influence cancer outcomes beyond perioperative bleeding control.</div></span></li><li><span>•</span><span><div>Evidence on TXA and cancer progression remains limited and conflicting.</div></span></li><li><span>•</span><span><div>TXA may reduce transfusion, an exposure linked to worse cancer outcomes.</div></span></li><li><span>•</span><span><div>VTE risk remains a key safety concern in oncologic TXA use.</div></span></li><li><span>•</span><span><div>More rigorous studies are needed to assess TXA in cancer surgery.</div></span></li></ul></div><div><div>Tranexamic acid (TXA) is widely used to reduce blood loss and red cell transfusion in major surgery. Its safety in oncologic surgery remains uncertain, given theoretical risks of venous thromboembolism (VTE) and tumor progression. We conducted an analytic review of clinical and laboratory evidence evaluating TXA in cancer surgery or cancer-relevant models. We performed a clinically focused review of experimental and clinical evidence examining TXA use in oncologic settings. Key influential studies were prioritized and supplemented by a structured literature search of MEDLINE, Embase, CENTRAL, and Web of Science from database inception through May 2025. Findings were synthesized narratively across preclinical, interventional, and observational evidence, with emphasis on clinical outcomes and biological plausibility. While retrospective and single-center clinical studies in cancer populations demonstrated reduced red cell transfusion with TXA, the oncology trials demonstrated decreased blood loss but no reduction in transfusion, suggesting that any effect is attenuated under modern perioperative practice. Across studies reporting VTE, postoperative DVT/PE rates were typically 0% to 3% and did not differ between TXA and controls. Only a small number of clinical studies evaluated oncologic outcomes, alssssl observational and underpowered, with no evidence of harm. Laboratory findings were equivocal, with some models showing increased invasion or migration at supratherapeutic concentrations, whereas others demonstrated neutral or protective effects. The impact of TXA on transfusion need in oncologic surgery is ambiguous, and recent randomized trials in oncology do not show reductions in allogeneic transfusion. Available data do not indicate increased VTE risk, and no clinical signals of oncologic harm have been observed, though evidence remains limited. Cancer-specific studies with long-term follow-up are needed to define oncologic safety and to clarify whether indirect effects through transfusion avoidance influence cancer outcomes.</div></div><div>Tranexamic acid (TXA) is widely used to reduce blood loss and red cell transfusion in major surgery. Its safety in oncologic surgery remains uncertain, given theoretical risks of venous thromboembolism (VTE) and tumor progression. We conducted an analytic review of clinical and laboratory evidence evaluating TXA i","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 3","pages":"Article 151009"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148399773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Should Transfusions of Donated G6PD-Deficient Donor Red Blood Cells Be Restricted to Improve Patient Safety? A Critical Review of the Current Literature","authors":"Matthew S Karafin, Richard O Francis","doi":"10.1016/j.tmrv.2026.151019","DOIUrl":"10.1016/j.tmrv.2026.151019","url":null,"abstract":"<div><div>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme deficiency and can cause significant hemolysis and anemia in individuals exposed to oxidative stress. During refrigerated storage after donation, red blood cells (RBCs) accumulate oxidative damage which adversely affects transfusion efficacy, with more severe effects on RBCs collected from G6PD-defienct donors. Although there are international recommendations to assess blood donors for G6PD deficiency and to decide on transfusing G6PD-deficient RBCs based on recipient characteristics, in the United States this is not routinely done. This review critically evaluates relative strengths and weaknesses of recent studies examining the post-transfusion circulatory survival of G6PD-deficient RBCs in healthy volunteers, in general patient populations, and in chronically-transfused patients. Although these studies uniformly suggest that transfusions of G6PD-deficient RBCs lead to less optimal outcomes, they have not led to a change in clinical practice. Remaining unanswered questions are also considered in the context of how a change in transfusion practice could become feasible in the future.</div></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 3","pages":"Article 151019"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trust Over Knowledge: Rethinking Donor Iron Supplementation Strategies in Modern Blood Services","authors":"RishiRaj Sinha","doi":"10.1016/j.tmrv.2026.150960","DOIUrl":"10.1016/j.tmrv.2026.150960","url":null,"abstract":"","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 2","pages":"Article 150960"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147312890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beyond Implementation: The Need for Validation, Equity, and Real-World Accountability in AI for Transfusion Medicine","authors":"Rishiraj Sinha , Manvi Talwar","doi":"10.1016/j.tmrv.2026.150990","DOIUrl":"10.1016/j.tmrv.2026.150990","url":null,"abstract":"","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 2","pages":"Article 150990"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biotin-Labeled Red Blood Cells in Transfusion Medicine","authors":"","doi":"10.1016/j.tmrv.2026.150992","DOIUrl":"10.1016/j.tmrv.2026.150992","url":null,"abstract":"","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 2","pages":"Article 150992"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147995780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fleur Krommendijk , Amber Meulenbeld , Katja van den Hurk
{"title":"Trust Over Knowledge: Rethinking Donor Iron Supplementation Strategies in Modern Blood Services—Authors’ reply","authors":"Fleur Krommendijk , Amber Meulenbeld , Katja van den Hurk","doi":"10.1016/j.tmrv.2026.150962","DOIUrl":"10.1016/j.tmrv.2026.150962","url":null,"abstract":"","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"40 2","pages":"Article 150962"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147613506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}