Blood Transfusion (BT) welcomes international submissions of papers on all fields related to Transfusion Medicine, Immunohematology, Hemostasis and Thrombosis. BT is the official journal of two European Scientific Societies BT is published in English (Supplements may be published in the original language) Free online access Impact Factor (2024): 2.3 The journal is indexed in PubMed-MEDLINE, Google Scholar, Embase and Scopus and PubMed Central. Official journal of Società Italiana di Medicina Trasfusionale e Immunoematologia) (SIMTI) and Sociedad Española de Transfusión Sanguinea y Terapia Celular (SETS).
Erratum: Quality and stability studies of red blood cell concentrates from umbilical cord blood compared to their adult counterparts
Results of red cell antibody screening assays from 2,500 laboratories in 10 external quality assessment programs: sensitivity for anti-D
Background - Red cell antibodies can cause severe or fatal hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. Screening for antibodies, such as anti-D, has been applied over decades for any transfusions and pregnancies. A comparison of sensitivities across laboratories is lacking for such antibody assays. Materials and methods - We investigated the detection rates for defined antibody concentrations of anti-D, the most common trigger of adverse outcomes. In a concerted effort among 10 providers of external quality assessment and proficiency testing programs, 4 spiked samples were tested by exactly 2,500 laboratories applying their clinical routine procedures, covering 4 test principles, more than 24 test cells, and diagnostic devices from 5 manufacturers. Results - The sensitivity of the assay depended on the test principle. Detection rates correlated with anti-D antibody concentrations: 0.1 IU/mL and 0.025 IU/mL can reliably be recognized. Some assays enabled detection at 0.01 IU/mL, and only a few at 0.005 IU/mL. Erythrocyte-magnetized technology and solid phase red cell adhesion performed better than various modifications of the column agglutination technology. The conventional test tube technology, depending on visual reading, was least sensitive. Discussion - The results show options for action to improve antibody detection, may support a practice change to optimize routine strategies of red cell antibody screening, and can guide studies to evaluate the clinical impact.
Lipidomic and metabolomic analysis of human erythrocytes during storage for transfusion applications
Background - The preservation of concentrated red blood cells (RBCs) is crucial for their vitality and functionality. During storage, various metabolic changes occur, such as the loss of ATP, diphosphoglycerate, and potassium, as well as oxidative damage to proteins, lipids, and carbohydrates. Lipids, the most abundant class of metabolites in cells, are essential for maintaining the integrity and function of the red blood cell membrane. This study aims to evaluate molecular changes and identify potential biomarkers to optimise RBC transfusion by analysing metabolic and lipid profiles of preserved RBC at different time points. Materials and methods - Thirty samples from 10 freshly collected RBC units from 10 donors, were collected at three time points: collection, after 20 days, and after 40 days, and stored properly. The RBCs were then centrifugated, and the pellet was stored at −80°C for the metabolomic and lipidomic analyses using liquid chromatography coupled with mass spectrometry. Results - Lipidomic analysis revealed a progressive reduction in major membrane phospholipid classes, including phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, and phosphatidic acids. At increased resolution, molecular-species-level analysis identified selective depletion of arachidonate-containing phosphatidic acid species alongside a concomitant increase in free arachidonic acid, indicating active phospholipid remodeling during storage. Metabolomic profiling confirmed previously described alterations in glycolysis, energy metabolism, and redox-related pathways and revealed coordinated changes in metabolites linked to phospholipid synthesis and turnover. Discussion - These findings confirm established features of RBC storage lesions while providing refined insight into membrane lipid remodeling at the molecular species and fatty acid building block levels. The integrated lipidomic and metabolomic approach highlights specific lipid signatures associated with RBC membrane aging, which may complement existing frameworks for studying storage-associated cellular changes and support future investigations linking molecular remodelling to functional RBC quality metrics.
Collection, production and storage of blood components
Patient autonomy and Patient Blood Management: lessons from the Pindo Mulla v. Spain Case
The Pindo Mulla v. Spain judgment (European Court of Human Rights, 2024) demonstrates that violations of patient autonomy may arise not from individual clinical decisions, but from inadequate procedural and institutional preparedness. The case involved a competent Jehovah’s Witness who received a blood transfusion despite her explicit refusal. From a transfusion medicine perspective, the judgment makes clear that respect for informed refusal depends on system readiness rather than ad hoc decision-making. The Court’s finding of a violation of Article 8 exposes cumulative failures, including insufficient Patient Blood Management (PBM) optimization, omission of available bloodless alternatives, and the absence of meaningful patient participation before judicial intervention. These shortcomings transformed an ethically manageable situation into a procedural emergency. PBM should be understood as an organizational framework that operationalizes respect for autonomy while fulfilling the duty to protect life, reconciling Articles 2 and 8 through institutional design rather than emergency exception.
Impact of 1- and 2-unit red blood cell transfusions on continuously monitored vital signs: a longitudinal study
Background - We measured trends in continuous vital sign parameters and hemoglobin concentration in adult patients before and after 1- and 2-unit red cell (RBC) transfusions. Materials and methods - A multi-center longitudinal study of 72 patients connected to a remote continuous monitoring service transfused 1 or 2 RBC units. Primary outcome was changes in heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2), and secondary outcome was changes in hemoglobin concentration. Results - Fifty-one patients received 1 RBC unit, 21 received 2 units. During the 10-hour pre-single-unit transfusion period, there were no clinically meaningful trends in HR (0.05, 95% CI, −0.36 to 0.46), RR (0.13, 95% CI, 0.02 to 0.25), or SpO2 (0.08%, 95% CI, −0.02 to 0.18). There were no clinically meaningful differences in trends in the 24-hour period post-single-unit RBC transfusion when compared to the pre-transfusion trend (HR: 0.03, 95% CI, −0.44 to 0.51; RR: −0.09, 95% CI, −0.22 to 0.05; SpO2: −0.15%, 95% CI, −0.27 to −0.02). The mean hourly hemoglobin trend 48 hours pre-single-unit transfusion was −0.07 g/dL (95% CI, −0.09 to −0.05) and 0.08 g/dL (95% CI, 0.05 g/dL to 0.10 g/dL) in the 48 hours post transfusion when compared to the pre-transfusion trend. Similar results were observed pre- and post-double-unit RBC transfusion. Discussion - Despite hemoglobin concentration declines pre-single and double-unit RBC transfusion, and expected increases post-transfusion, there were no clinically meaningful trends in vital signs in the 10 hours before single- or double-unit transfusion or changes in trend in vital signs 24 hours post-transfusion.
Blood donation Word-of-Mouth behavior among Chinese and Indian donors: an exploration with Australian donors
Background - Cultural diversity in a blood donor panel is vital for healthcare, especially in countries where multiple cultural groups are growing in representation and have unique phenotypes. Word-of-mouth (WOM) is considered a potentially powerful way to recruit diverse donors; however, donors seldom talk about blood donation. This study explores factors influencing positive WOM about blood donation among people within Chinese and Indian communities in Australia. Materials and methods - Six online focus groups were conducted with 35 donors (20 Chinese and 15 Indian) aged 18-57 who had donated in the past 12 months. Using thematic analysis, the factors that contributed and inhibited sharing WOM about blood donation were identified. Participants shared their WOM experiences, motivations, perceived barriers, and supports needed to enhance their WOM activities. Results - Donors from both cultural groups recognized the benefits of discussing blood donation, however their engagement varied. Most were reactive, responding to inquiries rather than initiating conversations. Their WOM behaviors were influenced by personal experiences, conversational context, and social connections. The main concern was being perceived as bragging, while motivators included altruism and professional links to healthcare. Significant cultural differences emerged: Indian participants were cautious about WOM to avoid personal health disclosures from recipients, while Chinese donors highlighted cultural perceptions of loss of vitality from donating, especially among older individuals, as a barrier to discussing donation. A proposed model of willingness to share WOM was developed based on individuals’ goals for sharing WOM and perceived agency to do so. Discussion - Strategies are needed to help donors view their role as including active support for blood donation. Tools and resources that give donors a "license" to initiate WOM discussions about blood donation, while addressing cultural misconceptions, may strengthen their confidence and agency to discuss blood donation.
Transfusion practice in elderly patients across surgical disciplines in Germany - a secondary data analysis of over 21 million patients
Background - Clinicians are increasingly confronted with elderly patients across nearly all surgical disciplines. Advanced age is an independent risk factor for complications, prolonged hospitalization, and particularly for red blood cell (RBC) transfusion. The elderly suffer more frequently from anemia, which is associated with higher perioperative transfusion requirements, increased complication rates, and mortality Surgical disciplines differ not only in primary diagnoses but also in the demographics of their typical patient population. Material and methods - Hospitalized surgical patients in Germany between January 1st, 2013, and December 31st 2022, were analyzed. Inclusion criteria: Age ≥65 years, surgical disciplines: General surgery, Gynecology, Cardiac surgery, Thoracic surgery, Oral and Maxillofacial surgery, Neurosurgery, Trauma and Orthopedic surgery, Urology or Vascular surgery. Exclusion criteria included unknown or overlapping surgical procedures. Risk factors, comorbidities, transfusion rates, bleeding, complications, and blood product use were assessed using ICD and OPS (the German national procedure coding system) codes. The primary endpoint was RBC transfusion rate; the secondary endpoint was preoperative transfusion rate. Results - A total of No.=21,143,317 patients were analyzed of which No.=2,640,608 (12%) received RBC transfusion. The highest transfusion rate was seen in Trauma and Orthopedic surgery (17.2% - No.=1,116,082). Trauma and Orthopedic surgery also had the highest risk (Odds Ratio [OR]) for RBC Transfusion (1.36 [1.35-1.36]). The highest preoperative transfusion rate was noted in general surgery, where 48.2% (No.=384,553) of the transfused patients received at least one RBC transfusion prior to surgery. Discussion - Our study revealed that the highest transfusion rate in elderly patients is in Trauma and Orthopedic surgery, while the highest rate of preoperative transfusion was seen in General surgery. It would seem worthwhile to reduce these rates wherever possible, and these are the disciplines which offer the most room for improvement and would thus benefit most from consistent establishment of PBM programs.
The effective use of platelet-rich plasma (PRP) in treating a severe traumatic knee injury in a child with hemophilia A
Platelet-rich plasma (PRP) is a therapy primarily used in orthopedics or dermatology to stimulate healing and promote tissue regeneration. There are rare cases in which it was used to treat traumatic injuries or wounds, but none in persons with hemophilia (PwH). Our young patient was admitted to emergency hospital following a blade injury to the knee. The wound was initially sutured but not treated with a coagulation factor concentrate. Subsequently, it became infected after surgery. The infection was complicated by significant skin and subcutaneous tissue loss. PRP was used to promote tissue regeneration. Three additional applications after first treatment were needed to repair the injury. Tissue regeneration began immediately and was completed after two weeks. No further therapies were required, and the child was discharged. PRP therapy is an interesting, safe, and effective approach for treating traumatic injuries in PwH. It could reduce recovery times and the need for clotting factor concentrates.
Precision Medicine and Patient Blood Management - A Good Pairing
Artificial Intelligence in Transfusion Medicine
Passenger lymphocyte syndrome after living-donor kidney transplantation with minor ABO incompatibility: a case report
Passenger lymphocyte syndrome (PLS) is an uncommon, immune-mediated hemolytic disorder that may develop after solid organ or hematopoietic stem cell transplantation when minor ABO incompatibility exists between donor and recipient. It is caused by donor-derived viable B lymphocytes producing antibodies against recipient erythrocyte antigens. We describe a 28-year-old female (recipient blood group A RhD-positive) who underwent living-donor kidney transplantation from her father (donor group O RhD-positive). Two weeks post-transplant, she presented with fatigue, right shoulder and scapular pain. Laboratory evaluation demonstrated severe normocytic anemia (hemoglobin 49 g/L), elevated lactate dehydrogenase and bilirubin levels, undetectable haptoglobin, and a strongly positive direct antiglobulin test (IgG and C3d). Elution studies identified anti-A antibodies bound to red blood cells, suggestive of PLS. Imaging excluded bleeding but revealed thrombosis of the right internal jugular and brachiocephalic veins. Management included plasma-exchange (PEX), high-dose corticosteroids, and transfusion of irradiated donor-type (group O RhD-positive) red cells. The patient showed progressive hematologic recovery with normalization of hemolytic indices and preserved graft function at hospital discharge. PLS should be considered in the differential diagnosis of acute hemolytic anemia occurring within the first three weeks after transplantation involving minor ABO mismatch. Early recognition through direct antiglobulin testing (DAT) is essential to guide transfusion strategy and immunomodulatory therapy. Combined PEX and corticosteroid treatment effectively reduced antibody-mediated hemolysis. Routine post-transplant DAT screening may facilitate prompt diagnosis and improve clinical outcomes in renal transplant recipients.
Assessing operational readiness for plasma fractionation within Indonesia’s National Transfusion Medicine System: a cross-sectional mixed-methods study
Background - Plasma-derived medicinal products (PDMPs) such as albumin, immunoglobulins, and clotting factors are essential in treating life-threatening conditions. Indonesia lacks local plasma fractionation capacity and relies heavily on imports, leading to high costs and financial strain on the National Health Insurance. Developing national plasma production capacity is vital for pharmaceutical independence and health system resilience. This study assessed the readiness of regional blood centers and hospital blood center in Indonesia as potential suppliers of plasma raw material for domestic PDMP production and identified logistical and governance challenges in the existing system. Materials and methods - A cross-sectional mixed-methods study was conducted in five institutions ‒four regional blood centers and one hospital blood center‒ across Java. Readiness was evaluated across three domains: preparation, inventory, and transportation. Instruments were adapted from WHO, LIAT, and LSAT guidelines, with expert-validated content. Content validity was ensured through expert panel review involving WHO and national regulatory representatives, and reliability was measured using the Kuder-Richardson Formula 20 (KR-20). Quantitative data were analyzed descriptively using Kruskal-Wallis and Dunn’s tests, while qualitative data were thematically analyzed. Results - The overall KR-20 was 0.821, indicating strong reliability (Preparation=0.801; Inventory=1.00; Transportation=0.856). No significant inter-institutional differences were observed (p=0.406), suggesting uniformly high readiness. Bias testing confirmed consistent scoring patterns. Discussion - This study provides a structured baseline assessment of Indonesia’s readiness to support domestic PDMP production, revealing strong preparedness across key operational domains. While readiness does not yet translate to full production capacity, these findings establish an evidence-based foundation for future implementation, investment planning, and governance reforms toward a sustainable and transparent plasma supply chain.
Organization and quality systems in transfusion medicine
Towards a value-based approach in hemophilia: indications from the FAR-BENE study
The significant improvements in hemophilia management and treatments observed in the last decade changed expectations of hemophilia community in terms of achievable health status but also raised concern on economic implications associated with these new approaches. In this context the need of new indicators for the desired health outcomes made achievable by the transformation of treatment has been developed and suggested in the literature, providing the basis for the development of value-based healthcare in hemophilia. The FAR-BENE (Pharmacoeconomic and Well-Being in Hemophilia) study, recently published, represents an important and timely effort to bridge this gap. Even with limits, the FAR-BENE study offers a clear signal of the need and possibility to move beyond the measure of factor consumption and bleeds and implementing a value-based approaches that integrates economics aspects with comprehensive, clinical and patient-centric outcomes. A further effort is now required by the healthcare system to create the appropriate conditions to adopt and implement standardized value-based approaches, ensuring the possibility of improving the patients’ health by maximizing the healthcare resources available.
Identification of a novel B allele with c.298T>A giving rise to a weak B phenotype in Chinese voluntary blood donors
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.
Rhnull phenotype caused by a novel RHAG allele, RHAG*c.640+1G>C, in a Chinese individual
Rhnull blood type is characterized by the complete absence of Rh antigens on red blood cells, a condition that can lead to notable morphological abnormalities. In this study, a patient with an Rhnull phenotype was identified through serologic testing. Sequencing of RHAG revealed a novel c.640+1G>C mutation, which was subsequently confirmed to be inherited from the father and transmitted to the children.
Exposure of red blood cell concentrates to temperatures below 0°C for a short period does not alter in vitro quality
Background - To guarantee the quality of red blood cell (RBC) transfusion, RBC concentrates (RCCs) are stored at 4±2°C. Deviations to this specification can alter the RBCs. Although the exposure to higher temperatures is well documented, the exposition to subzero temperatures has been less investigated. Materials and methods - RCCs (prepared from top-bottom kits and stored in saline-adenine-glucose-mannitol - SAGM) accidentally exposed to temperatures below 0°C were investigated in two regional blood services in Switzerland; Case 1: 1 h 52 min below 0°C (minimum of −5.7°C), and Case 2: 3 h 19 min below 0°C (minimum of −0.9°C). In case 1, 5 exposed and 5 unexposed RCCs were visually inspected for hemolysis or other alterations. Hemolysis was quantified in the 5 exposed RCCs and one control. In Case 2, 71 RCCs were analyzed at the time of the incident and at day 42 for hematological parameters and hemolysis. Ten RCCs were followed weekly for glucose, lactate, potassium levels and deformability. Results - Under these conditions no signs of out-of-specification hemolysis or RBC damages were observed. Nevertheless, a higher hemolysis was reported in 4-day-old RCCs exposed to subzero temperature compared to existing and age-matched controls. Storage lesions were equivalent to unexposed RCCs and to literature. Discussion - The two present real cases of RCCs exposure to temperatures below 0°C did not show damage to RBCs over storage. Even though the present work did not investigate the limits of RBCs sensitivity to cold temperature, it provides indications on the capability of RCCs to resist such type of storage deviation.
Evaluation of stored whole blood cellular components treated with bactericidal peptides at a higher concentration than required to assess the peptide compatibility with product quality
Background - Despite advancements in screening and pathogen detection, bacterial contamination of whole blood (WB) remains a rare but critical risk, typically originating from donor blood or skin-resident bacteria. While current pathogen reduction technologies (PRT) mitigate this risk, they often compromise blood quality relative to the untreated units. As an alternative, we recently evaluated two synthetic peptides, D-CONGA and D-CONGA-Q7 in WB at a concentration of ~8 μM for bactericidal efficacy and compatibility with WB hemostasis potential. However, evaluation of hemostasis property of WB alone is insufficient to ensure that endogenous red blood cells (RBC) and platelets are maintaining other critical functional parameters that are measurable in vitro. Materials and methods - We investigated the effects of these peptides on the WB endogenous RBC and platelets at ~2.5 times higher concentration (i.e., 20 μM) than what is required (8 μM) for complete bactericidal activity to test their compatibility limits. We investigated the performance of WB endogenous RBC resident hemoglobin oxygen affinity and glycolytic rate as well as WB endogenous platelet aggregation potential as part of monitoring the safety and compatibility profile of the peptides. Results - Our results support that even higher peptide concentrations do not significantly affect oxygen dissociation from red blood cells but do cause a slight deviation in P50 values and a marginal difference in glycolytic rate. Further, WB endogenous platelet aggregation is not affected by the peptide treatment with any of the aggregation agonists used. Discussion - Overall, we conclude that while higher peptide concentrations (20 μM) than required for bactericidal activity (~8 μM) may slightly affect glycolysis and the ability of red blood cells to dissociate from oxygen, platelet aggregation is not affected. This report clearly supports the potential safe use of these peptides for inactivating bacteria in WB without harming the product quality.
Identification and analysis of a novel ABO allele with c.959insC variant in a Chinese blood donor
Background - The mutation of ABO gene leads to the weakening of ABO antigen expression. The third-generation single-molecule sequencing technology is used to help accurately identify the variant blood group and analyze the molecular mechanism of antigen weakening. Materials and methods - The ABO blood group was identified by immunohematology, and the weak antigen was detected by absorption and elution technique. Finally, the full-length sequence of ABO gene was analyzed by the third-generation single-molecule sequencing technology, including promoter, exon, intron and regulatory region. Results - The proband was serologically identified as Ael subtype. Gene sequencing analysis showed that the genotype of the proband was ABO * O.01.01 / ABO * A.NEW heterozygous, carrying a novel mutation c.959 insC. Discussion - This study reports the discovery of a novel Ael blood group allele, which results in reduced expression of the A antigen on the red blood cell surface.
Appropriate preoperative transfusion requests: an unsolved issue
Nearly fifty years after Friedman et al introduced the Maximum Surgical Blood Order Schedule (MSBOS) to optimize preoperative blood ordering, inappropriate transfusion requests remain a widespread issue. Despite strong evidence showing that proper MSBOS implementation reduces blood product wastage, costs, and safety risks without compromising patient outcomes, many institutions continue to overestimate transfusion needs. The recent multicentre study by Contreras-Lopez et al. involving elective brain tumour surgeries in Spain revealed substantial inefficiencies, with over 83% of patients having blood reserved but only 6.6% actually transfused. The findings underscore the persistence of poor compliance with MSBOS principles and limited use of type-and-screen protocols, particularly in low-transfusion-risk procedures. Overordering is often driven by precautionary concerns but leads to unnecessary resource consumption and increased risk of mis-transfusion. To ensure appropriateness, MSBOS protocols must be data-driven, institution-specific, and integrated into hospital-wide quality improvement systems supported by electronic health record (EHR) technology. Continuous education, multidisciplinary collaboration, and the use of computerized crossmatching and remote electronic release systems have proven effective in improving compliance and efficiency. Overall, rationalizing preoperative blood ordering through updated, evidence-based MSBOS programs and proactive anaemia management is essential to enhance patient safety, resource utilization, and transfusion practice sustainability.
Improving blood safety: NAT-based detection of Plasmodium spp. in blood donors in endemic areas of Brazil
Background - Transfusion-transmitted malaria remains a significant challenge in endemic areas and is a leading cause of blood donation deferral. Rigorous clinical and molecular screening is essential to ensure the safety of blood components. The presence of low-density Plasmodium spp. parasitemia in asymptomatic individuals can compromise transfusion safety and perpetuate disease transmission. This study aimed to describe malaria positivity detected by the NAT PLUS HIV/HBV/HCV/Malaria kit (Bio-Manguinhos), as well as to characterize the epidemiological profile of blood donors and the main deferral causes at a reference blood center in the Brazilian Amazon. Materials and methods - This was a retrospective observational study using secondary data from the HemoSys database, which included sociodemographic variables, clinical screening, and self-reported malaria history from blood donors. Cases of clinical malaria were investigated among NAT PLUS-positive donors within six months before and after the reactive donation. Results - A total of 67,114 blood donors tested using the NAT PLUS assay were included. The median age was 35 years (IQR 25-43), with a predominance of male donors (65.1%). Most self-identified as mixed race (80.5%) and had completed high school (53.3%). Malaria-related factors accounted for 2.6% of deferrals (No.=27,434). Malaria positivity detected by NAT PLUS assay was 0.01% (8/67,114), with all reactive donors being asymptomatic at screening. Most positive cases (6/8) occurred during the low-transmission period (rainy season). One donor (12.5%) developed symptomatic malaria (P. falciparum), confirmed by thick blood smear and notified in the SIVEP-Malaria system shortly after donation. Discussion - Individuals testing positive for Plasmodium spp. by NAT PLUS assay may progress to clinical malaria post-donation, posing risks to both donor health and transfusion safety. The frequent absence of information on malaria exposure during clinical screening highlights the need for standardized protocols and molecular testing to improve early identification of at-risk donors in endemic regions.
Donor health beyond donation: cardiovascular risk factors in blood donor populations. A cross-sectional study
Background - Blood donors are often regarded as healthier than the general population, a phenomenon described as the “healthy donor effect”. This perception arises from strict donor selection criteria and routine pre-donation screening, yet these evaluations focus largely on hemoglobin, vital signs, and a short medical history, thereby providing only a partial assessment of donor health. As cardiovascular disease (CVD) remains the leading global cause of mortality, assessing cardiovascular risk factors in blood donors provides an opportunity to evaluate whether this group is genuinely healthier or simply appears so due to selection bias. Materials and methods - A cross-sectional study was conducted among 1,543 Slovenian blood donors. All donors completed a medical questionnaire, underwent a physical examination, and vital signs measurements. Body mass index (BMI) was calculated from self-reported weight and height. Information on diseases, medication use, smoking, and physical activity was also collected. A subgroup of 506 donors without reported illness and not taking medication was classified as “healthy”. This subgroup underwent additional laboratory investigations, including complete blood count, lipoproteins, and high-sensitivity C-reactive protein. A composite CVD risk score was developed by integrating traditional and novel risk factors. Results - Overall, 32% of donors reported at least one chronic condition and 19% reported medication use, most frequently antihypertensive therapy. Median BMI was 26.3 kg/m², with 56% of donors overweight or obese. Nearly 40% had elevated BP, including 7% with systolic BP ≥160 mmHg. According to the CVD risk score, 49% were low risk, 29% moderate, and 25% high, with men more often at increased risk. Discussion - Despite eligibility screening, many donors exhibited subclinical CVD risk factors. These findings confirm that transfusion services can contribute beyond donor and recipient safety, offering a valuable platform for prevention and early detection, and strengthening public health surveillance.
Severe hemophilia A with inhibitors and pancreatic cancer – when emicizumab is not enough
Short description Since the early 2000s, FVIII prophylaxis has been the standard for severe hemophilia A, but patients with inhibitors who failed immune tolerance induction (ITI) had no effective prophylaxis until emicizumab, which significantly reduced bleeding rates and improved quality of life. A 67-year-old man with severe hemophilia A and high-titer inhibitors, managed previously with bypassing agents, began emicizumab prophylaxis in 2021 and experienced over three years without bleeding, including safe dental procedures. In 2024, he was diagnosed with stage III pancreatic cancer, and despite emicizumab, he had multiple severe bleeding episodes during diagnostic and therapeutic procedures, requiring large doses of rFVIIa; bleeding ceased after stereotactic radiotherapy. This case highlights emicizumab’s transformative impact but also its limitations during major medical interventions, emphasizing the continued need for on-demand treatment and consideration of ITI even in the era of non-factor therapies.
Rare inherited autosomal bleeding disorders in women: sex-related bleeding, pregnancy and delivery. A narrative review
Rare inherited autosomal bleeding disorders (RAIBDs) are a heterogeneous group of coagulation diseases including rare bleeding disorders and inherited platelet disorders, characterized by a wide variability in frequency and severity of hemorrhagic symptoms. The management of women suffering from these disorders is very challenging due to sex-related bleeding, such as menstrual flow and hemorrhage events linked to pregnancy and delivery. Furthermore, in this subset of patients, there are open issues regarding the delivery mode, to preserve the newborn who could be affected by the same bleeding disorder. The purpose of this review is to explore evidence on the management of women suffering from RAIBDs in order to guide physicians taking care of this subset of patients. Heavy menstrual bleeding (HMB) is often the most frequent reported symptom and the reason for referral: its lack of prompt identification can lead to a delay of diagnosis; HMB often provokes iron-deficiency anemia, with a significant reduction of quality of life. HMB treatments are limited and based on limited efficacy data. The rarity of these coagulation defects poses a challenge in the management of pregnancy and delivery, especially if the bleeding disorder is not diagnosed prior to the physiological pregnancy-associated changes in hemostasis (which make the diagnosis more difficult); a careful collection of the hemorrhagic and family history is essential. Currently, there is only limited evidence about the management of RAIBDs during pregnancy and delivery, and the present clinical practice is often based on the current local policy.
Irregular antibodies in pregnancy during the universal anti-RHD prophylaxis era: a survey of Spanish Hospitals
Background - Although great advances have been made in the prevention of hemolytic disease of the fetus and newborn, especially for anti-D, irregular antibodies still appear. In order to ascertain the situation in Spain, we conducted a survey among hospitals treating pregnant women. Materials and methods - We sent a survey to Spanish public hospitals comprising demographical data (ethnicity, number of pregnancies, type of fertilization), characteristics of antibodies (specificity, number, antigenic compatibility), cause of alloimmunization and the clinical consequences (fetal death, icterus, anemia) between 2016 and 2021. We characterized the risk posed by antibodies and their clinical impact according to previously described criteria. Results - During the study period, 574,140 children were born in the responding hospitals. Antibodies were detected in 1,055 women with 1,112 pregnancies, resulting in a 0.19% alloimmunization prevalence. The most common antibodies were anti-D (No.=393, 28.7%), anti-c (No.=204, 14.9%), anti-E (No.=199, 14.6%), anti-M (No.=129, 9.4%), and anti-Kell (No.=114, 8.3%). Incorrect prophylaxis administration in the current or past pregnancy accounted for 88.6% of anti-D, and 12 (6.5%) arose from an RhD-positive transfusion. When analyzing incompatible pregnancies (No.=424; 38%), 103 (24.3%) presented severe or very severe hemolytic disease, most of which (No.=92, 89%) were produced by high-risk antibodies, while only 11 cases were caused by medium-risk antibodies. Discussion - The prevalence of irregular antibodies during pregnancy in Spain is lower than previously described for other Western countries. The most important antibodies are anti-D, anti-c and anti-K. More efforts to characterize antibodies should be made in order to reduce their prevalence and clinical impact.
Molecularly confirmed para-Bombay (Ah) secretor phenotype with FUT1 c.328G>A and FUT2 c.357C>T mutations: first case report from India
A 35-year-old woman presented with symptoms of anemia and hemoglobin of 5.5 g/dL. The patient's blood sample was subjected to standard serological blood grouping, using both tube and column agglutination techniques. Group I discrepancy was found between cell grouping (O Rh D positive) and serum grouping (A group). Serological tests revealed no detectable H antigen on red cells despite presence of normal ABO antigens in the secretions, indicating a para-Bombay Ah secretor phenotype. Blood group genotyping revealed homozygosity for both the FUT1 c.328G>A mutation and the FUT2 c.357C>T mutation, leading to diminished H antigen expression in RBC and intact secretor function, respectively. This rare case of para-Bombay (Ah) secretor phenotype expands the spectrum of H-deficient phenotype reported from India and highlights complexity of blood group typing and importance of molecular diagnostics in rare phenotypes.
RH gene inversion-recombination as a major mechanism of the D-- phenotype in China
Background - The D-- phenotype is an extremely rare RhCE variant characterized by the complete absence of RhCE antigens in the Rh blood group system and is associated with a highly complex molecular mechanism. In this study, several D-- individuals with discrepancies between phenotypic and genotypic results were analyzed, and a complex RH gene inversion-recombination variant with a novel breakpoint was identified via multi-platform analyses. Materials and methods - Six D-- individuals from the Chinese population were collected. The full-length sequences of the RHD, RHCE, and RHAG genes were amplified, and long-read haplotype sequencing was performed using PacBio technology. Complex structural variations in the RH gene were detected through Bionano Optical Genome Mapping (OGM). Lastly, fusion regions in the RHCE haplotype were amplified and sequenced using PacBio technology and PCR-SBT. Results - PacBio third-generation haplotype sequencing (TGS) suggested the presence of potential structural variants. Subsequently, Bionano optical genome mapping (OGM) identified a complex gene inversion and recombination structural variant, designated RHCE*Ce(1-2)-D(3-10)-TMEM50A-Ce(10-8)-Ce(3-10). Moreover, a novel fusion breakpoint was validated by PacBio haplotype sequencing and PCR sequencing-based typing (PCR-SBT). The structural inversion, which originated within intron 7 of the RHCE gene at chr1: 25377650, was rejoined to intron 2 at chr1: 25404500, forming a novel breakpoint. Finally, all D-- individuals in this study harbored this complex structural variation with an identical breakpoint position. Conclusion - The RH gene inversion and recombination may represent a prevalent molecular basis for the D-- phenotype in the Chinese population. These findings expand our understanding of the molecular mechanisms underlying the Rh blood group system and hold significant implications for transfusion safety in individuals with this rare D-- phenotype.
Complete D epitope expression of the most common weak D types 15, 25, 33, and 72 in the Chinese population
Background - The most common weak D type 1, 2, and 3 individuals in the Caucasian population can be safely treated as D+ patients. However, the management of the common weak D type 15 in the East Asian population and the frequent weak D types 25, 33, and 72 in the Chinese population remains controversial. Materials and methods - D epitope expression in individuals with weak D types 15, 25, 33, and 72 was assessed using an anti-D panel (D-Screen) via both hemagglutination and sensitive adsorption/elution methods. Furthermore, these four variant RHD constructs and one wild-type (wt) RHD construct were cotransfected with the wt RHAG construct into HEK 293T cells in vitro. After transfection, the surface expression of the RhD antigen was assessed via flow cytometry with a panel of monoclonal anti-Ds. Results - Routine serological D epitope typing with D-Screen revealed that the red blood cells of weak D types 15 (No.=3), 25 (No.=3), 33 (No.=4), and 72 (No.=3) individuals were negatively agglutinated with one or multiple monoclonal anti-Ds. For the D epitopes undetectable by hemagglutination testing, positive reactions were obtained in the adsorption/elution tests when the corresponding non-reactive monoclonal anti-Ds were used. In vitro expression analyses revealed that all four weak D variant constructs expressed all tested D epitopes comparable to those observed with the wt RHD construct. Discussion - The complete repertoire of D epitope expression was observed both in weak D types 15, 25, 33, and 72 individuals in vivo and expression analysis in vitro. This provided evidences that individuals with these four weak D types, similar to D+ patients, can receive D+ red blood cell transfusion and do not require Rh immunoglobulin prophylaxis.
No bleeding during a dialysis catheter insertion in a patient with INR 3.2 due to acute liver dysfunction
We report a case of a 61-year-old female admitted to the intensive care unit (ICU) with circulatory failure, acute liver dysfunction and stage 3 acute kidney injury (AKI) secondary to severe acute pancreatitis (SAP). Despite a markedly elevated international normalized ratio (INR >3) and uremia (urea >100 mg dL-1), a dialysis catheter was inserted without any bleeding. Viscoelastic hemostatic assay (VHA) demonstrated preserved clot propagation and firmness and impaired clot initiation. Based on ROTEM results and absence of signs of clinical bleeding, we opted against prophylactic transfusion of fresh frozen plasma (FFP) and proceeded with catheter placement. No bleeding was observed during or after the procedure. This case supports growing evidence that conventional coagulation tests (CCTs) like INR are unreliable predictors of bleeding in acute liver failure. VHAs offer a global and functional assessment of hemostasis, revealing rebalanced or hypercoagulable profiles otherwise masked by CCTs. Current guidelines increasingly discourage routine FFP transfusion prior to invasive procedures, advocating individualized risk assessment. Our report contributes to ongoing discussion about optimizing transfusion practices and procedural safety in critically ill patients with elevated INR and supports the broader integration of VHAs into ICU decision-making.
Optimal model for predicting intraoperative blood transfusion in elective surgery patients: a comparative study of eight machine learning methods
Background - To identify the optimal machine learning model for predicting intraoperative blood transfusion requirements in elective surgery patients by systematically evaluating eight algorithms. Materials and methods - A retrospective cohort of 1,500 elective surgery patients was screened, with 1,017 meeting inclusion criteria. Demographic (gender, age, height, weight), preoperative (liver, cardiac, pulmonary, coagulation functions), and intraoperative indicators (surgery grade, anesthesia score, estimated blood loss, vital signs) were collected. After univariate analysis, 20 significant variables were selected for modeling. The dataset was split 7:3 into training and testing sets. Eight models −Random Forest (RF), Generalized Linear Model (GLM), Support Vector Machine (SVM), Gradient Boosting Machine (GBM), k-Nearest Neighbors (KNN), Neural Network (NNet), λ determined by cross-validation (LASSO), and Decision Tree (DT)− were trained using five-fold cross-validation. Performance was evaluated based on the area under the receiver operating characteristic curve (ROC-AUC), precision-recall curves (PR-AUC), residuals, and variable importance. Results - In the training set, RF achieved the highest AUC (1.000), followed by GBM (0.992) and SVM (0.987). In the testing set, RF maintained superior performance (AUC=0.992), with high precision-recall (AUC-PR=0.988) and minimal residuals. Key predictors included preoperative hemoglobin (preHGB), EBL, and coagulation markers (preAPTT, preDD). Discussion - RF is the most reliable model for intraoperative transfusion prediction, offering high accuracy and clinical interpretability. This study provides a data-driven tool to optimize transfusion strategies and reduce adverse outcomes.
Turoctocog alfa pegol versus recombinant factor VIII-Fc fusion protein: a head-to-head pharmacokinetics comparison
Our series of five cases enabled a direct comparison of the pharmacokinetic (PK) profiles of turoctocog alfa pegol versus efmoroctocog alfa, a recombinant a factor VIII‐Fc fusion protein, performed in the same subjects with severe hemophilia A within a short time-frame. Half-life values were significantly longer, by about 1 hour, with turoctocog alfa pegol than with efmoroctocog alfa. The estimated time spent with FVIII levels above 5% when infusing every 4 days was significantly longer with turoctocog alfa pegol. When feasible, the possibility of executing a PK curve should be considered, in order to use the parameters obtained as the main indicators and predictors of coagulation support.
The effects of pathogen reduction technology on apheresis platelet concentrates stored in PAS
Background - The impact of pathogen reduction technology (PRT) such as Mirasol, and the effect of platelet additive solutions (PAS) on the activity and hemostatic profile of transfused apheresis platelets remain largely unknown. Aim of this study was to assess the in vitro hemostatic and metabolic profile of Mirasol treated platelets in PAS during a 7-day storage period. Material and methods - Ten split bags containing apheresis platelets stored in PAS were split into two groups; control platelets (10 units) and PRT-treated platelets (10 units). In vitro evaluation of the platelet components was performed on the 1st, 3rd, 5th, and 7th days of the storage period. Several metabolic parameters including pH, glucose, and lactate levels were evaluated, while assessment of their hemostatic capacity was performed using light transmission aggregometry (LTA) and viscoelastic studies such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG). Last, Annexin V levels were measured though flow cytometry for evaluation of platelet activation. Results - Clot strength, as reflected by the maximum clot firmness (MCF) and the maximum amplitude (MA) parameters of the viscoelastic studies was significantly decreased in the PRT-treated platelets compared to the control platelets (p<0.05). Clot strength based on MCF and MA values was also found to be decreasing over storage time in PRT-treated platelets (p<0.001), while this was not evident in control platelets. Moreover, the comparison between pH, glucose, and lactate levels were indicative of increased metabolic activity in PRT-treated platelets compared to control platelets (p<0.001). Annexin-V was significantly higher in PRT-treated platelets compared to control platelets on the 7th day of the storage period (p<0.001). Discussion - The results of this study indicate that increased PSL induced by PRT treatment leads to a decreased in vitro platelet hemostatic efficacy and increased metabolic activity. However, the clinical impact of these alternations needs further investigation.