Blood donor recruitment, retention, and safety face mounting challenges from an aging donor base and declining donation rates, and there is need for innovation in donor engagement. Machine learning (ML) offers tools to model donor behavior, physiology, and risk, but the maturity, methodological rigor, and translational readiness of this literature have not been systematically characterized. This study aimed to systematically identify and critically appraise studies applying ML methods to blood donation. We conducted structured searches of PubMed for articles published since January 1, 2018 (search date May 7, 2026). Studies were included if they explicitly applied ML; addressed donor safety, engagement, recruitment, retention, health, or adverse reactions; and demonstrated empirical or real-world relevance. Included studies underwent critical appraisal of design, predictors, outcome definition, model development, validation strategy, and practical implications. Of 54 articles identified in systematic search, 5 were selected, addressing donor return prediction, lipemic plasma triglyceride screening in a small, highly selected cohort, anticipatory vasovagal reaction prediction from facial thermal imaging using neural networks, cross-country hemoglobin deferral prediction with model exchange, and externally validated iron recovery prediction using ensemble models. Gradient-boosted and tree-based ensemble models predominated, with SHAP-based interpretation, cross-validation, and external or multi-national validation being used in studies. Common limitations included small or highly preselected samples limiting generalizability; a lack of external validation; underuse of decision-analytic or hard operational endpoints; and minimal discussion of deployment, workflow integration, or ongoing evaluation. ML applications in blood donor services remain at an early, exploratory stage with promising but heterogeneous performance.

Transfusion-related acute lung injury (TRALI) is a potentially fatal blood transfusion complication that is characterized by noncardiogenic pulmonary edema within 6 hours post-transfusion. Specific therapies are not available, thus understanding the pathophysiological mechanisms is essential. Currently, our understanding of the TRALI pathophysiology is based on a 2-hit requirement. The first hit constitutes a priming of the immune system associated with systemic inflammation. The second hit comes through transfused antibodies reactive against recipient leukocytes and/or endothelium, or biological response modifiers. Interestingly, recent case reports suggest a so far underrecognized occurrence of TRALI by a reverse mechanism in the presence of leukoreduced products. In this so called "reverse TRALI," preexisting recipient antibodies react with transfused components such as cells or soluble antigens, triggering pulmonary endothelial cell damage culminating in pulmonary edema through predominantly unknown and unexplored mechanisms. In this review, we have summarized the published literature with suspected reverse TRALI cases, consisting of 11 clinical reports of 25 patients in total (1976-2022). Remarkably, we observed a trend in reverse TRALI cases attributed to granulocyte transfusions in 13 out of 25 cases (52%). The pathomechanisms of reverse TRALI are largely uninvestigated. To start shedding light on this, we furthermore propose several potential mechanisms for reverse TRALI based on literature. We have stratified on transfused soluble antigens, in relation to recipient cells such as polymorphonuclear leucocytes, macrophages/monocytes, and to pathogenic processes including antibody-Fc mediated complement activation, production of reactive oxygen species (ROS), formation of neutrophil extracellular traps (NETs) and secretion of pro-inflammatory cytokines. Our hypothesized pathomechanisms of reverse TRALI are a starting point to investigate this transfusion complication, with potential diagnostic, preventive and therapeutic implications.

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 × 10[6] 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.

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.

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.

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.

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 (P = .003). This reduction was particularly evident in alloimmunized patients compared with the nonalloimmunized group (P = .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.

This single-center, prospective, randomized controlled study evaluated the effects of stress ball and music interventions-targeting sensory distraction-on anxiety, distress, and pain levels in platelet apheresis donation (PAD). The study included 102 first-time donors aged 18 to 55 at a university hospital blood transfusion center. Participants were randomly assigned to three groups: stress ball (n = 34), music (n = 34), and control (n = 34). Data were collected using the Donor Information Form, Beck Anxiety Scale (BAS), Visual Analogue Scale, Distress Thermometer (DT), and Donor Monitoring Chart. During PAD, the stress ball group received a stress ball and the music group listened to instrumental music for 30 minutes, while the control group received routine care. The groups were similar in sociodemographic characteristics (p > .05); 43.1% were aged 20-30 years. The music group showed the greatest reduction in BAS scores (p < .001) and had the lowest post-intervention DT score (1.17 ± 1.56). In the stress ball group, heart and respiration rates decreased significantly after intervention (p = .008). The control group experienced a slight increase in pain scores, whereas both intervention groups reported no pain. Although anxiety and distress levels were mild before donation, both stress ball and music interventions significantly reduced these outcomes after PAD. Distraction-based methods, such as stress balls and music, may support emotional well-being during PAD and enhance the donor experience.

Primary thrombocytosis is associated with increased risk of thromboembolism and bleeding. Therapeutic plateletpheresis (TPP), capable of rapid, transient platelet (Plt) count reduction, is employed as an emergency intervention for symptomatic thrombocytosis while awaiting the therapeutic effect of medical cytoreductive therapy. Nonetheless, the effect of TPP on outcomes and optimal role for TPP remain poorly understood. Critical analytic review of highest-pertinence and -quality articles was performed with the goal of establishing current knowledge gaps to direct original case data collection. Retrospective review of TPP procedures at six United States sites over ten years was performed. Pre-TPP symptoms, medical cytoreduction, adverse events (AEs), and 30-day post-TPP outcomes were analyzed. Critical analytic review revealed no randomized controlled trial (RCT) or controlled trials (CT) of TPP versus first-line medical therapies, and insufficient information on symptoms, goals, criteria-based determination of course, and post-TPP outcomes. New data presented here details 45 adult patients receiving TPP for thrombocytosis. TPP was performed rarely (of n = 6 sites, median 4.5 TPP/10 years, range 4-20). The most frequent diagnosis was myeloproliferative neoplasm (MPN) (34, 75.6%). The most frequent symptoms were any neurologic symptoms (present pre-64.4% of TPPs). TPP goals were commonly Plt-related (n = 85, 94.4% total TPP) and were met in 72.9% of TPP with stated Plt-related goals. Often, (n = 11/50 single TPP or series) TPP was begun or continued despite resolution of the stated indication for TPP. AE occurred during 20% of TPP and were predominantly hypocalcemia related (17/18, 94.4%). Four patients died within 30 days post TPP, three of stroke, one of a non-stroke neurologic complication. All deaths were deemed unrelated to TPP. Critical analytic reviews revealed no RCTs or CTs, a paucity of data on TPP goals and prescribed courses, and significant variability in AE reporting. Little information on long-term outcomes is available. Without controlled evidence supporting clinical outcome benefit of TPP for symptomatic thrombocytosis, utilization is expected to be rare and guideline-informed, following careful consideration of known risk in the setting of unclear benefit.