Individuals under 30 represent a small share of the already limited blood donor pool, making their recruitment and retention critical to maintaining a sustainable blood supply. This article presents a narrative review of 13 recent studies (published since 2023) on engaging younger blood donors and discusses the effectiveness of emerging interventions. We find that existing interventions primarily target three mechanisms: (1) awareness, (2) engagement, and (3) emotional arousal. Findings suggest that educational approaches can increase knowledge and reduce misconceptions, social and community-based interventions can initially strengthen motivation and participation, and interventions targeting anxiety can improve donation experiences, particularly among younger and first-time donors. However, evidence of sustained behavioural change remains limited, as most studies rely on short-term outcomes and self-reported intentions rather than observed donation behaviour. The findings suggest that increasing young donor participation requires coordinated action across educational institutions, blood collection agencies, and social communities, as each is positioned to influence different stages of the donor journey. At the same time, the review reveals a structural “vacancy” in donor development: while responsibility for influencing young donors is distributed across multiple actors, no actor is clearly positioned to coordinate and sustain these efforts. We argue that strengthening the future donor base requires not only effective interventions but also system-level approaches that address this coordination gap.
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 several studies. Common limitations included small or highly pre-selected samples limiting generalizability, limited external validation, underuse of decision-analytic or hard clinical outcomes, 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.
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.
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.
Artificial intelligence (AI) and machine learning (ML) are increasingly promoted to enhance transfusion and patient blood management, yet real-world implementation remains rare. We reviewed recent exemplar studies reporting prospective deployment with workflow integration to examine translational features, barriers, and enablers of AI/ML integration. On June 18, 2025, we searched PubMed and Web of Science for articles from January 2022 onward. Of 1243 records screened and 31 full texts reviewed, 3 studies met inclusion criteria. The exemplars comprised: (1) a laboratory-embedded tool predicting low ferritin in anemic adults, which during a 21-day deployment identified additional iron deficiency relevant to pretransfusion optimization; (2) a patient-facing smartphone application estimating hemoglobin from fingernail images, adopted nationally by >200,000 users with potential implications for anemia screening; and (3) a clinician-facing smartphone decision support tool predicting resuscitation needs in trauma, piloted across 5 centers with acceptable feasibility and user satisfaction in a transfusion-intensive setting. Common enablers included alignment with clinical need, use of existing data infrastructure, interpretable tree-based models, and early stakeholder engagement. Persistent barriers were data quality and governance, limited generalizability, and absence of economic evaluation. Importantly, no study demonstrated improvement in clinical outcomes or cost. For clinical adoption, AI tools must integrate into routine workflows with clear safety, monitoring, and regulatory plans. Future research should apply implementation frameworks from the outset, evaluate downstream impact on transfusion practice and outcomes, and prioritize scalable approaches such as laboratory-embedded analytics, interoperable decision support, and patient-centered digital tools.
Many blood establishments have hemoglobin (Hb) measurement policies to prevent anemia in blood donors. However, despite evidence of iron deficiency (ID) in donors with normal Hb levels, only few blood establishments have implemented iron management strategies. Recently, the Dutch and French national blood services implemented ferritin-guided donation interval policies, albeit in different ways. While in the Netherlands ferritin is measured every 5 donations, in France ferritin measurements are performed in predefined risk groups. We compared rates of ID (ferritin <15 ng/mL), low ferritin (15-30 ng/mL), and low Hb between the Netherlands and France before and after policy implementation. We also compared donor return rates and ferritin levels after ferritin-based deferrals. We found that before the policy change there were differences in rates of ID and low ferritin, but Hb deferral rates were very similar. After the policy change, more ferritin measurements were performed in the Netherlands, but both countries had similar ID rates (∼4.5% and ∼1% of measured females and males, respectively). Return rates within one year after the end of deferral for ID were similar in both countries (∼60% for females and ∼80% for males), but French donors had higher ferritin upon return despite the shorter deferral period. Because this is an observational study using retrospective data, and due to a lack of the standardization of ferritin measurements, comparisons need to be interpreted with caution. Nonetheless, the results offer valuable insights concerning the impact of ferritin-guided donation intervals for blood establishments that consider the implementation of similar policies.
Maternal alloantibody-induced hemolytic disease of the fetus and newborn (HDFN) remains a significant concern worldwide. Alloimmune HDFN can be pathogenetically named by the specific alloantibodies involved. Moreover, four mechanistic pathway types are generally recognized in clinical practice: classical or extravascular hemolysis; immune-pressure-escaped, also known as antibody-mediated antigen-modulation; apoptotic or dysplastic, and failed transaction. Another proposed pathway is worthy of discussion: lactation-mediated. Management strategies for alloimmune HDFN should take account of these underlying mechanisms.
