Blood Transfusion

AI and transfusion medicine in Europe: why public leadership cannot wait

Massimo La Raja — 2026-07-07

The absence of a validated, large-scale artificial intelligence tool in transfusion medicine reflects the structural, public-service design of blood systems rather than any technological limitation. For these reasons public blood services must lead AI development within the regulatory window created by the SoHO Regulation.

Identification of a novel B allele with c.298T>A giving rise to a weak B phenotype in Chinese voluntary blood donors

Jiancheng Liu — 2026-02-26

This study utilized third-generation single-molecule sequencing to identify a B subgroup in the ABO blood group system. The subject was a voluntary blood donor from China. Full-length sequencing of the ABO gene via the PacBio platform revealed that the individual carries a novel ABO allele, c.298T>A (p.Phe100Ile). This mutation was not detected in a cohort of 60 randomly selected blood donors, and pedigree analysis indicated it was inherited from the father. The mutation is predicted to disrupt the structure of glycosyltransferase and impair its catalytic activity, leading to weak expression of the B antigen. This study is the first to report the association between the c.298T>A mutation and a weak B subtype, thereby expanding the understanding of the genetic diversity within the ABO system and highlighting its significance for transfusion safety.

Variation in eluate volume during DNA extraction does not affect eluate concentration of plasma-derived DNA

Frederik Banch Clausen — 2026-07-15

We have observed significant variation in the volume of eluate from the process of DNA extraction. Such variation may affect the precision of downstream, quantitative DNA measurements. Therefore, we investigated this eluate variation and assessed the potential correlation between DNA concentration and eluate volume in repetitive testing of pooled human plasma sample material. The mean eluate volume of expected 60 µL eluate was 63.3 µL with a coefficient of variation of 6.6%. However, although the total amount of DNA varied and correlated with eluate volume (Spearman rank correlation: r = 0.67), the DNA concentration remained unchanged (p=0.0991), (Spearman rank correlation: r = 0.35). This finding showed that variation in the 60 µL elution volume from the QIAsymphony instrument does not affect downstream, quantitative DNA measurements.

Evaluation of protease resistant synthetic antimicrobial peptides as a new approach methodology to mitigate bacterial growth in ex vivo human platelet concentrates

Joseph Jackson — 2026-06-24

Background - Maintaining the safety of platelet concentrates (PCs) is a significant challenge in transfusion medicine, as room-temperature storage (22°C) increases the risk of transfusion-transmitted bacterial infections (TTBIs). This study evaluates a New Approach Methodology (NAM) for pathogen reduction using two protease-resistant antimicrobial peptides (AMPs), D-CONGA and D-CONGA-Q7.

Materials and methods - PCs were experimentally contaminated with Escherichia coli and Staphylococcus epidermidis. The bactericidal efficacy of the AMPs was assessed at a concentration of 8 µM, which is the minimum inhibitory concentration (MIC) that we established in our previous report for the two bacteria used in this study. To determine the biocompatibility and safety margins, the effects of these peptides (at 8 µM and a 2.5× higher concentration of 20 µM) on in vitro platelet activation, aggregation, and plasma coagulation functions (aPTT) were evaluated.

Results - At 8 µM, both AMPs achieved a 5-log₁₀ reduction in bacterial load within 2-3 hours of treatment. Biocompatibility testing revealed that concentrations up to 20 µM did not negatively impact platelet activation or aggregation potential. While 8 µM and 4 µM concentrations remained compatible with normal clotting activity, the 20 µM dose significantly elevated clotting times; however, this effect was partially reversed through peptide absorption using a cation exchange resin.

Discussion - D-CONGA and D-CONGA-Q7 at a concentration of 8 µM serve as effective bactericidal agents in PCs without compromising essential functional attributes. These findings support the potential of these AMPs as a viable strategy to enhance the safety and quality of stored platelets for transfusion.

Characterization of growth factors in platelet-poor plasma for eye drop applications from umbilical cord blood and from allogeneic adult donor serum

Larysa Mykhailova — 2026-07-15

Background - Serum eye drops obtained after the coagulation of platelet-rich, adult donor blood (AB-S) are currently used to promote corneal healing in dry eye disease (DED). Recently, unique immunomodulatory factors that could prove clinically useful in DED have been identified in platelet-poor plasma from cord blood (CB-PPP). In this descriptive, non-comparative pre-clinical study, we determined the growth factor (GF) content in CB-PPP and AB-S to expand the current knowledge on the clinical potential of blood derived eye drops.

Materials and methods - CB-PPP (No.=20) was prepared from anticoagulated CB by differential centrifugation using commercial BioNest ABC kits. AB-S (No.=6) was prepared from clotted 450 mL blood collections using commercial transfer bags. Epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (bFGF), platelet derived growth factor isoforms (PDGF-AA, -AB, -BB) were quantified by Luminex technology.

Results - Median EGF, VEGF and PDGF-AA, -AB and -BB (pg/mL) were lower in CB-PPP than in AB-S: 5.45 vs 224.0; 35.83 vs 401.26; 362.05 vs 2480.44; 197.06 vs 624.14; 1097.11 vs 2836.29, respectively. Conversely, median bFGF was about 9-fold higher in CB-PPP than in AB-S: 10.07 vs 1.13. High variability was observed between individual samples.

Discussion - This study expands current knowledge on blood-derived products for ophthalmic applications. The observed high inter-sample GF variability requires the development of standard procedures of unit pooling in view of clinical applications.

Erratum to: Rhnull phenotype caused by a novel RHAG allele, RHAG*c.640+1G>C, in a Chinese individual

Luisa Stea — 2026-09-18

n/a

RBCs of Asian-type DEL do not undergo antibody-mediated phagocytosis by macrophages

Qi Ren — 2026-06-24

Background - In the Rhesus (Rh) blood group system, D is the most immunogenic antigen. RhD-negative patients with anti-D must be transfused RhD-negative red blood cells (RBC) to avoid hemolytic transfusion. RBC of Asian-type DEL phenotype are typed as RhD-negative by routine blood group serological methods because they have very weak expression of D antigen. The prevalence of Asian-type DEL phenotypes was 30% in RhD-negative Chinese donors. Therefore, this DEL type can be transfused to RhD-negative patients with anti-D. However, there is a lack of direct evidence regarding the safety of this practice and potential mechanisms in act.

Materials and methods - The proportion of Asian-type DEL donors that serologically tested RhD-negative was investigated by using genotyping. Furthermore, a model system for in vivo clearance was established to assess antibody-mediated phagocytosis of Asian-type DEL RBC by macrophages.

Results - We identified six serologically RhD-negative donors, 16 Asian-type DEL donors according to polymerase chain reaction polymerase chain reaction with sequence-specific primers (PCR-SSP), and six PCR-SSP
RhD-positive donors across various regions in China. Our study revealed that
antibody-mediated RBC clearance was not observed following co-culture of opsonized Asian-type DEL RBC with macrophages.

Discussion - Incompatible transfusion of Asian-type DEL RBC may not result in significant RBC clearance.

The RHCE*CeRN allele: molecular junction characterization and frequency distribution in Sub-Saharan African populations

Assia Hadjkali — 2026-05-29

Background - The CeRN (RHCE*02.10) allele was described as resulting from hybrid RHCE-D-CE genes, involving either exon 4 alone or exon 4 and part of exon 3. No solution allows to distinguish between the two reported CeRN alleles. The objectives of this study were to determine the existence of both alleles, their genetic sequence and their frequencies.

Materials and methods - We investigated 17 heterozygous CeRN samples and 10 homozygous CeRN samples, and described the junction between the RHCE and RHD genes. Analysis combined classical PCR associated with Sanger sequencing, and Oxford Nanopore NGS applied to long-range PCR. We also explored CeRN allelic frequency in sub-Saharan populations from the 1000 Genomes Project and the International Genome Sample Resource.

Results - One CeRN allele sequence was observed, involving exon 4 alone with an RHCE-RHD junction approximately 400 base-pairs upstream of exon 4. We observed the CeRN allele in Gambian ethnic groups, with a maximum allelic frequency of 6.0% in the Fula group.

Discussion - The CeRN allele involving exon 4 and part of exon 3 was not observed here, supporting at least a low frequency, as our sample size limited the power to investigate this putative second CeRN variant. The homogeneity of the CeRN sequence observed in DNA samples and the high allelic frequency are consistent with a single genetic founder event in the Fula ancestral group. Nearly 20% of individuals in The Gambia have abnormal hemoglobin. Knowledge of CeRN genetic architecture and frequency may have significant implications for more precise molecular diagnostics and transfusion therapy.

The probabilistic pipeline developed here, based on subset of samples for which both DNA and WGS data were available, showed that WGS low-coverage data can be used to investigate complex genetic variants in population studies.

Salvianolic acid B alleviates red blood cell storage lesion with GPX4 preservation and reduced lipid peroxidation

Chuan'ai Chen — 2026-06-19

Background - Red blood cell (RBC) storage lesion is a cascade of biochemical and physical alterations that impair transfusion efficacy and safety. This study explored the role and underlying mechanism of salvianolic acid B (Sal B) against RBC storage lesion, with a specific focus on a ferroptosis-like process.

Materials and methods - RBC from healthy volunteers were stored in MAP additive solution for 35 days, and samples were analyzed at weekly intervals. Ferroptosis was determined by the levels of cytosolic reactive oxygen species (ROS), antioxidant enzymes superoxide dismutase and glutathione peroxidase, 4-hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), and glutathione peroxidase 4 (GPX4). Storage lesion was evaluated by erythrocyte morphology, hemolysis rate, microvesicle formation, phosphatidylserine exposure, lactate dehydrogenase release, osmotic fragility, and Band 3. Ferrostatin-1 was used to verify the involvement of ferroptosis.

Results - The results demonstrated a time-dependent escalation of both storage lesion and ferroptosis, evidenced by biochemical changes such as increased hemolysis, phosphatidylserine exposure, ROS accumulation, 4-HNE and MDA, as well as a reduction in antioxidant capacity and protein level of GPX4. Ferrostatin-1 treatment effectively mitigated pathological changes, suggesting that ferroptosis-associated pathways may contribute to storage lesion. Notably, Sal B supplementation correlated with reduced ferroptosis markers and mitigation of storage lesion, as evidenced by preserved GPX4 levels and reduced lipid peroxidation.

Discussion - This study demonstrates that a ferroptosis-like process of lipid peroxidation contributes to RBC storage lesion, with GPX4 regulating erythrocyte stability. Sal B alleviates storage lesion in parallel with preservation of GPX4 and reduced lipid peroxidation, providing a potential strategy to improve the quality of stored blood.

Blood donor deferral patterns in Iran: six-year national analysis (2016-2021)

Leila Kasraian — 2026-06-11

Background - Blood donor deferral has a significant impact on the adequacy of blood supply and donor retention globally. Understanding deferral patterns is crucial for optimizing donation services and ensuring a sustainable blood supply in middle-income countries with established voluntary donation systems. The aim of this study was to analyze the prevalence, temporal trends, and causes of blood donor deferrals across Iran using a comprehensive 6-year national dataset (2016-2021).

Material and methods - We conducted a retrospective analysis of all voluntary blood donation attempts recorded in Iran’s “Negareh” database (2016-2021).
Data included demographics, donation history, deferral status, and provincial variations. Non-parametric tests and chi-square analyses were performed (p<0.05).

Results - Among 12,966,574 donation attempts, 2,161,808 individuals (16.67%) were deferred: 14.37% temporarily and 2.30% permanently. Deferral rates varied significantly by experience: 32.19% for first-time donors, 18.18% for repeat donors, and 8.98% for regular donors (η²=0.24, p<0.001). Female donors had higher deferral rates than males (30.68 vs 14.08%; odds ratio=2.70, p<0.001). Provincial rates ranged from 11.60% to 26.90%, inversely correlating with the Human Development Index (r= -0.67, p<0.001). Primary deferral reasons were high-risk behaviors (27.80%), general health unfitness (21.60%), and donor record issues (16.89%).

Discussion - Iran’s 16.67% deferral rate falls within global ranges but shows potential for optimization. The predominance of temporary deferrals (86.2%) and their association with modifiable factors suggest that targeted interventions could reduce deferrals by 2-3% while maintaining safety. Gender-specific prevention of anemia, enhanced preparation of first-time donor, and province-specific approaches could improve the donor experience and blood supply sustainability.

Frequency of type 2N von Willebrand disease among patients with mild or moderate factor VIII deficiency in an 18-month period in Iran

Behnam Azari — 2026-05-28

Background - Type 2N von Willebrand disease (VWD) increases the clearance rate of factor VIII (FVIII) in patient’s plasma, leading to clinical symptoms and laboratory findings similar to those of mild or moderate hemophilia A. Differentiating between these conditions is crucial for genetic counseling and treatment. This research aims to use genetic analysis to distinguish type 2N VWD from mild or moderate FVIII deficiency.

Materials and methods - During 18 months, suspected type 2N patients with mild or moderate FVIII deficiency, were selected from those referred to the Iranian Blood Transfusion Organization (IBTO) coagulation laboratory. Exons 18, 19, and 20 of the VWF gene were sequenced using Sanger's method. Subsequently, sequenced data were analyzed using NCBI's BLAST database and Chromas Pro.

Results - In the current study of 35 participants with mild or moderate FVIII deficiency, 5 were found to have type 2N VWD mutations. The mutations detected were p.Arg816Gln (No.=3) and p.Thr789Pro (No.=2), which are common in Iran. Three patients were misdiagnosed with hemophilia A at a young age, while 2 were not diagnosed until later in life.

Discussion - The current study discovered that 14.2% of the participants carried known type 2N VWD mutations, a higher prevalence compared to previous studies using a similar approach. Additionally, the study indicated that the limited availability of accurate diagnostic tests for type 2N VWD in our country could lead to a high probability of misdiagnosing or underdiagnosing patients with this condition.

Statistical quality control practices in a sample of Spanish Blood Establishments: a mixed-methods exploratory study

Hector Sarmiento Palao — 2026-09-18

Background - The European Directorate for the Quality of Medicines & HealthCare (EDQM) provides guidance for statistical quality control in blood component manufacturing, including recommendations for sampling and statistical process control. However, the extent to which these recommendations are implemented in routine practice remains unclear.

Materials and methods - We conducted a sequential explanatory mixed-methods study among professionals working in blood establishments, recruited through the Spanish Society of Blood Transfusion blood processing working group. Phase 1 was a cross-sectional survey (10 responding centers across 10 autonomous communities; response rate 77%). Phase 2 comprised semi-structured interviews with a purposive sample of survey respondents (No.=7). Survey findings informed the interview topic guide. Thematic analysis followed the Braun and Clarke approach. Findings from both phases were integrated using a joint display.

Results - Respondents represented centers with varied production volumes, and most had more than 6 years of experience (80%). Use of statistical quality control methods was limited: 90% reported using descriptive statistics only and 10% used control charts. For sample size determination, 80% applied fixed production percentages without formal statistical justification. Spreadsheet-based workflows with custom formulas predominated (90%). Key challenges included determining sample size and laborious report generation (both 80%). Interviews highlighted uncertainty about sampling adequacy, potential for earlier trend detection, perceived complexity of guidance, and the need for interpretive decision support. All participants expressed interest in automated approaches.

Discussion - Among participating centers, variation in the implementation of statistical quality control practices relative to EDQM recommendations suggests opportunities for improved harmonization. Automated tools that embed recommended sampling and monitoring methods may support implementation, although larger studies are needed to estimate prevalence at national level.

Transfusion risk assessment for cesarean delivery: a preoperative tool to guide blood utilization

Rosa F. Drummond — 2026-08-06

Background – Cesarean delivery is performed in approximately one-third of pregnancies in the United States and is associated with an increased risk of intrapartum and postpartum hemorrhage. Routine crossmatching of blood for all cesarean deliveries requires substantial resources and may not be necessary for every patient. We aimed to identify preoperative and intrapartum predictors of intraoperative blood transfusion and develop a practical risk stratification tool to support perioperative blood preparation.

Materials and methods – We conducted a retrospective cohort study including 3,033 cesarean deliveries performed at a university medical center between 2018 and 2022. Multivariable logistic regression with bootstrap internal validation (10,000 replicates) was used to derive a weighted transfusion risk score. Model performance was assessed by discrimination and calibration across predefined risk groups.

Results – Intraoperative transfusion occurred in 114 cases (3.8%). Independent predictors were placenta previa (aOR 5.14), prior blood transfusion (aOR 4.18), preoperative hemoglobin <11 g/dL (aOR 3.06), suspected intraamniotic infection (aOR 2.43), cervical dilation ≥6 cm (aOR 2.33), uterine fibroids (aOR 2.23), vaginal bleeding (aOR 2.04), and multifetal gestation (aOR 1.83) (all p<0.05). The model demonstrated good discrimination (AUC 0.75). The risk score stratified patients into low-, medium-, and high-risk groups with observed transfusion rates of 2.1%, 5.4%, and 15.1%, closely matching predicted probabilities of 2.1%, 5.8%, and 15.0%, respectively. Using a cut-off score of 4, specificity (91.7%) and negative predictive value (97.4%) were high, whereas sensitivity (37.7%) and positive predictive value (15.4%) were low.

Discussion – This simple risk score, based on routinely available preoperative and intrapartum factors, may help identify patients at low risk for intraoperative transfusion, allowing more selective blood preparation, improved resource allocation, and more efficient utilization of blood products during cesarean delivery while supporting individualized clinical decision-making.