SARS-CoV-2 infection is associated with a broad spectrum of red blood cell (RBC)-directed immune responses, ranging from isolated direct antiglobulin test (DAT) positivity to autoimmune hemolytic anemia (AIHA) and transfusion-related diagnostic challenges. This narrative review integrates current evidence on the mechanisms underlying these abnormalities, their clinical manifestations, and their implications for transfusion medicine. Molecular mimicry, bystander B-cell activation, complement dysregulation, oxidative membrane injury, and structural erythrocyte remodeling appear to represent interconnected mechanisms promoting immune recognition and altered function of RBCs. DAT positivity is frequently observed in hospitalized patients with COVID-19, often in the absence of clinically significant hemolysis, emphasizing that a positive DAT should not be considered synonymous with AIHA. Autoantibodies, complement deposition, and occasional alloimmune responses may complicate antibody identification, compatibility testing, and selection of appropriate blood components. Available evidence remains limited by heterogeneous study designs and the predominance of observational studies and case reports. Recognition of RBC-directed immune responses as part of COVID-19-associated immune dysregulation may improve interpretation of immunohematological findings, facilitate appropriate transfusion support, and help distinguish clinically significant immune hemolysis from isolated serological abnormalities.
The Rh-null phenotype is the rarest known red blood cell phenotype and is characterised by the complete absence of Rh antigens. During pregnancy, women with the Rh-null phenotype face unique challenges related to alloimmunisation against high-prevalence Rh antigens, haemolytic disease of the fetus and newborn, and the extremely limited availability of compatible blood for maternal or neonatal transfusion. We conducted a structured narrative review to identify published reports describing pregnancy-related or neonatal outcomes associated with the Rh-null phenotype, focusing on maternal antibody status, transfusion management, fetal monitoring, intrauterine intervention and maternal and neonatal outcomes. Eight reports published between 1983 and 2024 were identified. Anti-Rh29 was explicitly reported in three cases, whereas additional reports described panreactive antibody patterns consistent with antibodies directed against high-prevalence Rh antigens. Clinical outcomes ranged from mild neonatal haemolysis to severe fetal or neonatal disease. One pregnancy required intrauterine transfusion for severe fetal anaemia, and another neonate underwent repeated exchange transfusions because of severe haemolytic disease. Antenatal autologous blood donation was reported in one case as a proactive transfusion strategy. Pregnancy in women with the Rh-null phenotype requires advanced immunohaematologic investigation and specialised transfusion support. Early identification of Rh-null status, comprehensive antibody evaluation, coordinated maternal-fetal surveillance and proactive transfusion planning are central to management, ideally through multidisciplinary collaboration and access to rare donor resources.
OBJECTIVES:To evaluate anti-CD38 antibody candidates for their ability to bind to DTT-treated CD38 and red blood cells (RBCs). BACKGROUND:Dithiothreitol (DTT) treatment of RBCs is routinely used to denature CD38 and mitigate interference from anti-CD38 antibodies, such as daratumumab and isatuximab, in immunohematology testing. However, new anti-CD38 antibodies are in development, some of which may be directed against linear or otherwise DTT-resistant epitopes. METHODS/MATERIALS:Anti-CD38 antibody candidates were titrated in an enzyme-linked immunosorbent assay (ELISA) to assess their ability to bind to untreated and DTT-treated recombinant CD38. Antibody binding was subsequently confirmed by flow cytometry of RBCs. Daratumumab and felzartamab were then tested on a panel of native and DTT-treated RBCs in the indirect antiglobulin test (IAT). RESULTS:All antibodies except felzartamab failed to bind to DTT-denatured CD38 in ELISA at concentrations up to 1.25 μg/mL. Flow cytometry confirmed this binding pattern. In the IAT, some DTT-treated cells remained positive with felzartamab, despite being negative with daratumumab. CONCLUSION:Not all epitopes of anti-CD38 antibodies are fully DTT-sensitive. This has important implications for handling of anti-CD38 antibody induced interference in immunohematology, and raises the question of whether DTT is an adequate solution for interference mitigation.
BACKGROUND:Artificial intelligence (AI) is increasingly applied to blood-demand forecasting, donor management, inventory optimisation, wastage reduction and transfusion-related decision support; however, routine implementation remains limited. OBJECTIVES:To review current applications of AI in blood inventory management and transfusion support and identify the principal barriers to safe and sustainable implementation. METHODS:A focused narrative review informed by structured searches of PubMed, Scopus, EBSCO and Google Scholar, supplemented by targeted searches of transfusion-specific and healthcare AI implementation literature. Evidence was synthesised thematically. RESULTS:Published studies demonstrate technical feasibility across forecasting, donor-return prediction, inventory management and clinical decision support. Major implementation barriers include limited external and prospective validation, incomplete reporting, data-access and privacy constraints, poor interoperability, limited explainability, workforce training gaps and unclear governance. CONCLUSIONS:The principal challenge is no longer developing predictive models but integrating them safely and sustainably into routine transfusion services. Future progress requires multicentre evaluation, privacy-preserving data collaboration, workflow-integrated design, role-specific training and explicit governance with continued human oversight.
Viral hepatitis remains a serious risk to transfusion safety, despite being considerably reduced by donor screening. Objectives: The aim of this study was to evaluate the seroprevalence of HBV and HCV among asymptomatic blood donors in Saudi Arabia in the past 15 years (2010-2025). A literature search has been conducted on seven databases. Prevalence rates with 95% confidence intervals (CIs) were pooled via a random effects model. Twelve studies, examining 597 820 blood donors, were included in this study. The overall pooled prevalence rate of HBV and HCV among blood donors was 0.455% (95% CI: 0.334%-0.619%) and 0.195% (95% CI: 0.130%-0.292%), respectively. Although a high heterogeneity was detected across studies (I2 >80%, p = 0.000), sensitivity analysis revealed strong reliability, and no publication bias was detected. Subgroups and meta-regression analyses demonstrated that publication period, geographic location, and diagnostic methods were the main factors contributing to heterogeneity in prevalence estimates for HBV and HCV. According to our findings, the prevalence of positive blood donors for HBV and HCV is low across Saudi Arabia. We suggest that vaccination campaigns and public education regarding the modes of transmission should be improved in order to reduce the prevalence of blood-borne viruses.
OBJECTIVES:To highlight tranexamic acid (TXA) as 'just one thing' that every hospital could implement to reduce surgical bleeding and blood transfusions. BACKGROUND:TXA is a low-cost antifibrinolytic agent that inhibits the breakdown of fibrin blood clots. Developed in Japan in the 1960s, it has been shown to reduce surgical bleeding. TXA is also effective in traumatic and postpartum haemorrhage, with no proven increase in thrombosis. METHODS:Evidence from clinical trials, national guidelines, and policy reports was reviewed, including NICE recommendations and the UK Infected Blood Inquiry report. Patterns of TXA use and barriers to implementation were examined. RESULTS:There is strong evidence for the safety and effectiveness of TXA in surgery. However, despite inclusion in NICE guidelines since 2016, approximately one quarter of eligible surgical patients in the UK do not receive TXA, with similar underuse reported internationally. This results in missed opportunities to improve patient outcomes and reduce costs. The UK Infected Blood Inquiry recommended inclusion of TXA on surgical checklists, supported by regular audit and reporting. CONCLUSION:TXA represents an effective intervention to improve surgical outcomes and reduce transfusion. Increased uptake requires stronger leadership, audit systems, training, patient advocacy and alignment of clinical incentives with evidence-based practice.
BACKGROUND AND OBJECTIVES:The D- - phenotype is an exceptionally rare Rh configuration characterised by the expression of the D antigen but absence of all RHCE-encoded antigens. A few molecularly defined cases have been documented globally. MATERIALS AND METHODS:Gel microcolumn techniques were employed in this work to conduct serologic testing. Genotyping using ID RHD XT and ID CORE XT assays was performed, after which next-generation sequencing was performed on the RH promoter, exons 1-10 and introns 2-3 to enable definitive alleles to be identified. RESULTS:Serologic phenotyping showed D+ C- c- E- e-. Molecular analysis identified homozygosity for the RHCE*CeN.08 allele (RHCE*02N.08) a hybrid in which RHCE exons 3-9 are replaced by the corresponding RHD sequence together with two conventional RHD*01 alleles, consistent with the D- - phenotype. CONCLUSION:This is the first molecularly confirmed D- - donor reported in Saudi Arabia and the wider Middle East, and the first description of the RHCE*CeN.08 allele in this region. The finding extends the geographic distribution of this rare hybrid and underscores the value of combined serologic and high-resolution molecular testing for identifying and supporting D- - donors and patients.
BACKGROUND:Restrictive transfusion strategies and patient blood management programs increasingly recommend administration of single-unit red blood cell (RBC) transfusions followed by reassessment. However, clinicians often lack objective indicators to determine whether additional transfusion may subsequently be administered after the initial unit. Early haemoglobin response may provide clinically useful information regarding post-transfusion haematologic response and the likelihood of repeat transfusion. METHODS:We conducted a prospective observational cohort study including 518 hospitalized adults who received single-unit RBC transfusion. Haemoglobin concentrations for the primary analysis were measured at baseline and 24 h following transfusion. The primary predictor variable was the 24-h haemoglobin increment (ΔHb24). The primary outcome was repeat RBC transfusion within 48 h. A multivariable logistic regression model incorporating haemoglobin response and clinical variables was developed. Model performance was evaluated using receiver operating characteristic analysis, calibration assessment, and decision curve analysis. RESULTS:Among the 518 patients included in the study, 42 (8.1%) received repeat transfusion within 48 h. Patients who received additional transfusion demonstrated significantly smaller haemoglobin increments compared with those who did not. In multivariable analysis, ΔHb24 emerged as the strongest independent predictor of repeat transfusion, with increasing haemoglobin increments associated with lower risk. The prediction model demonstrated moderate discrimination (AUC 0.74) and acceptable calibration. Risk stratification showed that patients with ΔHb24 <1 g/dL had substantially higher probability of repeat transfusion, whereas those with ΔHb24 >1.5 g/dL had low risk. Decision curve analysis demonstrated positive clinical net benefit across clinically relevant threshold probabilities. CONCLUSION:Early haemoglobin response may provide clinically useful prognostic information regarding repeat transfusion risk following single-unit RBC transfusion. These findings support structured reassessment following single-unit transfusion and demonstrate that early haemoglobin response may assist in identifying patients more likely to receive repeat transfusion.
OBJECTIVE:To characterise a Thai patient with a para-Bombay phenotype associated with homozygosity for a variant FUT1 allele and explore the underlying mechanism of reduced enzymatic activity. BACKGROUND:The para-Bombay phenotype is a rare red blood cell phenotype characterised by absent or markedly reduced ABH antigens on erythrocytes, with preserved expression in secretions, typically resulting from FUT1 mutations affecting α1,2-L-fucosyltransferase 1 (α1,2FucT1). MATERIALS AND METHODS:Serological testing was performed using standard methods. ABO, FUT1 and FUT2 genotypes were determined by whole-exome and Sanger sequencing. Structural modelling of the FUT1 variant was conducted using AlphaFold3 and ChimeraX, and functional effects were predicted using ProtVar. RESULTS:Serology identified a para-Bombay Bh phenotype with anti-HI and autoantibodies. Genotyping revealed homozygosity for ABO*B.01, FUT1 c.658C>T (p.Arg220Cys; rs574691621; FUT1*01W.09), and FUT2 c.390C>T (a silent variant, p.Asn130). Structural modelling suggested that the p.Cys220 substitution does not alter overall protein conformation or stability but may impair substrate binding and local intermolecular interactions. CONCLUSION:This report presents the first Thai case of para-Bombay Bh phenotype associated with homozygosity for the weakened FUT1*01W.09 allele. In silico modelling predicted that the variant impairs α1,2FucT1 activity and substrate binding without compromising protein stability, supporting safe transfusion practice.
BACKGROUND:Postpartum haemorrhage (PPH) accounts for approximately 27% of maternal deaths worldwide and often requires blood transfusion, along with its associated risks. In resource-rich settings like South Korea, transfusion disparities persist, highlighting the need for predictive tools to optimise patient blood management (PBM). OBJECTIVE:To apply machine learning (ML) to rank predictors of transfusion in PPH using national claims data. METHODS:This was a retrospective cohort study of 123 763 women with PPH (2017-2019) from the National Health Insurance Service (NHIS) database (97% population coverage) in South Korea. The dependent variable was transfusion (yes/no). We used 48 independent variables (demographics, obstetric status, medications and comorbidities) derived from ICD-10/ATC codes. The random forest model (100 trees, Gini standard impurity criterion) was trained with 80% of the data and validated with 20% of the data after random split (area under the receiver operating characteristic curve [AUC] is a model performance metric). Permutation importance rankings were used for predictors; Shapley Additive Explanation (SHAP) values assessed directional associations and interactions. RESULTS:The transfusion rate was 6.7% (8308/123 763). The model achieved an AUC of 77.0% (95% confidence interval: 76.9-77.2). The top 10 predictors by variable importance were coagulopathy (0.311), placenta accreta (0.146), placenta previa (0.129), caesarean section (0.048), uterine atony (0.045), preterm delivery (0.041), age (0.037), vaginal laceration (0.029), iron use (0.025) and socioeconomic status (0.020). SHAP analysis confirmed a positive effect (e.g., maximum SHAP for placenta accreta = 0.2582), and the synergistic interaction between placenta accreta and coagulopathy amplified the risk. CONCLUSION:Coagulopathy and placental abnormalities are the most important drivers of transfusion in PPH. Explanatory ML enhances risk stratification beyond traditional models, informing PBM protocols to curb abuse and inequity. Potential integration into NHIS systems could protect maternal outcomes globally.
BACKGROUND:Transfusion-associated graft-versus-host disease (Ta-GvHD) is a rare, usually fatal complication of transfusing cellular components, prevented by irradiation. Congenital heart disease (CHD), particularly DiGeorge syndrome (del22q), may be associated with severe T-cell immunodeficiency and Ta-GvHD risk. British Society for Haematology guidelines (BSH, 2020) recommended targeted use of irradiated components for CHD based on immunological assessment; guideline adherence was unknown. OBJECTIVES:To understand UK use of irradiated components for paediatric CHD surgery and barriers to BSH guideline implementation. METHODS:An electronic survey distributed to the 11 UK paediatric cardiothoracic surgical centres (January-March 2024 inclusive). RESULTS:Of the 11 centres, 9 (82%) responded. Naïve T-cell enumeration, the BSH recommended test, was available to 8/9 (89%), but used in 4/9 (44%). 4/9 (44%) and 5/9 (56%) centres were willing to provide non-irradiated components to neonates and children >28 days of age. Of these, 1/4 (25%), 1/5 (20%), and 4/5 (80%) (for neonates, young children, and children from 2 years) required criteria additional to BSH guidelines. 8/9 (89%) centres reported ongoing barriers to guideline implementation, particularly challenges around pathway development and timely naïve T-cell enumeration. CONCLUSION:Overuse of irradiated components in surgery for patients with congenital heart disease is high: only 1/3 of paediatric cardiac centres adhered to BSH guidance. Reasons included difficulties in immunological diagnostic pathway development. Collaboration between paediatric cardiothoracic, transfusion and immunology teams is required to address this.
OBJECTIVES:To assess the impact of the individualised risk-based donor selection guidelines on deferral of blood donors at donation sessions in England. BACKGROUND:From June 2021, the 3-month deferral for sex between men was replaced by an individualised risk assessment known as FAIR (For the Assessment of Individualised Risk). Assessing the impact of deferral at donation informs donor and policy management. METHODS:Data were obtained from the NHS Blood and Transplant donor management system for deferrals associated with FAIR deferral codes or injecting drug use after FAIR implementation, 14 June 2021 to 13 June 2023. Rates for each deferral category were estimated by age group, sex, ethnic group, and donor type. Pre-donation forms were reviewed for evidence of multiple deferrable behaviours, and return rates were calculated for temporarily deferred donors. RESULTS:Over 2 years, 286 donors were deferred on-session due to FAIR (9.0 donors per 100 000 donations made). Highest adjusted incidence rate ratios of deferral were seen in first-time, male, 17- to 24-year-old, and Mixed and Other ethnicity donors. Multiple FAIR deferrals were observed in 10 donors. Of 220 temporarily deferred donors, 56.8% returned to donate within 6 months. CONCLUSION:The impact of FAIR on donation session appears low, supported by good return rates. First-time, male, and younger donors were most affected. Multiple FAIR deferrals in a donor were rare, suggesting donors at higher risk were not attending to donate. Clarity on deferral application may aid donors and staff to defer appropriately. Further investigation is needed to determine levels of ineligible donation.
BACKGROUND:Thrombocytopenia arises from heterogeneous inherited and acquired disorders, and identifying the underlying platelet clearance mechanisms remains challenging. Platelet desialylation, characterised by loss of sialic acid and consequent exposure of terminal β-galactose residues recognised by the Ashwell-Morell receptor, represents an alternative pathway of hepatic platelet clearance. This study aimed to validate a modified platelet desialylation test (PDT) and assess its applicability in multitransfused, alloimmunized, and hereditary thrombocytopenia patients as a functional in vitro assay to detect plasma-induced platelet desialylation and explore its potential as a complementary biomarker of platelet clearance mechanisms. METHODS:PDT performance was evaluated using plasma from 20 healthy donor pools, 10 antibody-positive refractory patients, and 15 individuals with hereditary thrombocytopenias by FITC-RCA-I flow cytometry. Analytical validation included assessment of reproducibility, incubation time, lectin concentration, and ratio-based result interpretation. RESULTS:β-Lactose showed significantly lower expression mean fluorescence intensity (MFI) than both untreated reference control and neuraminidase-treated conditions (p < 0.00001), whereas patient plasma exhibited higher fluorescence than the reference control (p < 0.0001). A 1 h incubation using 0.3 μL per reaction RCA-I-FITC stock solution (5 mg active conjugate/mL) provided stable and reproducible discrimination. In inherited thrombocytopenias, 66.7% of patients were PDT-positive despite HLA/HPA antibodies being detected in only 13.3%. PDT-positive samples showed increased desialylation-associated MFI (p = 0.002) with a strong correlation between MFI and ratio (ρ = 0.877). The assay required approximately 4 h and cost US$3.62 per test. CONCLUSION:The PDT is a practical, reproducible, and cost-effective assay capable of detecting physiologic, enzymatic, and immune-mediated platelet desialylation, providing a complementary biomarker for investigating thrombocytopenic disorders.
BACKGROUND:Transfusion-associated circulatory overload (TACO) prevention requires identification of susceptible patients and enactment of appropriate mitigation strategies. We implemented a clinical decision support (CDS) tool at our institution to reduce TACO occurrence by alerting transfusing clinicians to at-risk patients. METHODS AND MATERIALS:A CDS tool was designed to screen patient charts for TACO risk factors (age > 60, renal/cardiac impairment and prior TACO) at the time of inpatient blood component ordering through the electronic health record (EHR). The presence of risk factors triggered a Best Practice Advisory (BPA) pop-up featuring mitigation strategies. TACO rates and frequencies were compared pre- and post-BPA implementation using a Z-test. RESULTS:TACO as a proportion of transfusion reactions decreased 40% from 9.6% (406/4208) to 5.8% (47/804) in the 941 days after BPA implementation (z = 3.44, p = 0.00056). TACO frequency decreased 44% from 1 of 11.2 days to 1/20.0 days post-BPA (z = 4.00, p < 0.00001), while overall reaction frequency decreased 8% from 1 of 1.08 days to 1 of 1.17 days (z = 7.31, p < 0.00001). Among 47 post-BPA TACO events, 38 were subjected to the CDS algorithm, with the BPA firing for 4 of 36 (11%) of cases with TACO risk factors. CONCLUSIONS:TACO rates decreased at our institution following BPA implementation, despite BPA under-firing. Ongoing monitoring for BPA sustained effects is needed.
OBJECTIVE:To investigate the incidence and risk factors of Passenger Lymphocyte Syndrome (PLS) following ABO minor-incompatible lung transplantation. METHODS:A retrospective analysis was performed on 211 lung transplantations conducted between January 2022 and July 2025, including 58 cases involving ABO minor-incompatibility. The diagnosis of PLS was established based on evidence of haemolysis, a positive direct antiglobulin test (DAT), and confirmation of donor-derived antibodies. Clinical characteristics and outcomes were compared between the PLS and non-PLS groups using statistical analyses. RESULTS:The overall incidence of PLS was 3.32% (7/211), with a markedly higher rate of 12.07% (7/58) observed among ABO minor-incompatible transplants. Of the seven PLS cases, six occurred in O-to-non-O donor-recipient pairs. Risk factor analysis revealed that female sex (p < 0.001), bilateral lung transplantation (p = 0.027), and preoperative anaemia (p < 0.001) were significantly associated with the development of PLS. Furthermore, patients with PLS experienced several adverse postoperative outcomes, including lower nadir haemoglobin levels (43.50 g/L vs. 77.00 g/L in controls, p = 0.001) and platelet counts (29.00 × 109/L vs. 101.00 × 109/L, p = 0.001), substantially higher median red blood cell transfusion requirements (23.25 units vs. 0.00 units in controls, p < 0.001), and prolonged median hospital stays (75.50 days vs. 32.00 days, p = 0.002). CONCLUSION:PLS occurs at a relatively high frequency following ABO minor-incompatible lung transplantation. It is associated with risk factors such as female sex, bilateral lung transplantation, and preoperative anaemia, and contributes to more pronounced postoperative declines in haemoglobin and platelet levels, increased transfusion requirements, and extended hospitalisation.
BACKGROUND:In India, approximately 26.2 million units of blood are required annually; however, 5.83 million units were collected in 2021. 18% of blood donors in India are women, demonstrating an untapped donor pool, but their attitudes towards donation have not been explored. OBJECTIVES:The objectives of this study are to explore women's attitudes and barriers to blood donation in New Delhi from the perspective of blood bank workers. METHODS:This is a qualitative study involving blood bank workers. Twenty-five government blood banks in New Delhi were contacted and three participated. Convenience sampling selected 14 participants and semi-structured face-to-face interviews took place. Inductive thematic analysis was used. RESULTS:Attitudes towards blood donation were classified into two themes: responsibility and fear. Blood bank workers suggested women believed blood donation was harmful and it was not their responsibility. Barriers to women donating blood were classified into two themes: social factors and deferral. Social factors, such as family, patriarchal society, and the role of women, reduced the exposure of women to blood donation; therefore, limiting knowledge and the opportunity to donate. Deferral due to anaemia was another barrier. CONCLUSION:This study suggests that women's perceived responsibility and fears may stem from inadequate exposure to blood donation due to women's societal roles. Social influences and anaemia can pose barriers to women donating blood. However, these opinions are from blood bank workers and not the general population; therefore, further research is required. Educational campaigns for both sexes could reduce stigma around women donating blood.
