ABO blood group discrepancies in healthy individuals were caused by body-wide chimerism and mosaicism. They can be evaluated with new diagnostic options for disease-related cell clones that are typically associated with mosaicism. The observations raise the attention for sporadic mixed-field observations of any blood group antigen. Commentary on: Dauber et al. Body-wide chimerism and mosaicism are predominant causes of naturally occurring ABO discrepancies. Br J Haematol 2024 (Online ahead of print). doi:10.1111/bjh.19618.

The use of uncrewed aerial vehicles (drones) has increased over the last decade. However, their application in healthcare has not been fully examined, in part, due to regulations preventing flight beyond the visual line of sight. This prospective randomised controlled laboratory study aimed to determine whether the in vitro quality of packed red blood cell components is maintained when transported by drone, beyond visual line of sight. Ten identical pairs of packed red blood cell units were randomly allocated to transport by drone or by ground vehicle (1:1, allocation concealment) 68 km between two hospitals in Northumbria, UK. Markers of blood component quality were compared at 8, 14, 28 and 35 days following blood unit manufacture. There was no statistical difference in haemolysis, potassium concentration, total haemoglobin, glucose and lactate, haematocrit and mean cell volume, between the two groups, up to the date of unit expiry. The temperature of the packed red blood cell units did not deviate outside the recommended 2-10°C for transportation, regardless of the allocated group. Blood component transport was faster by drone, but did not reach statistical significance. This study demonstrates the feasibility and safety of flying blood components by drone between hospitals in the United Kingdom.

Sickle cell disease (SCD) affects two-thirds of African and Indian children. Understanding the molecular mechanisms contributing to oxidative stress may be useful for therapeutic development in SCD. We evaluated plasma elemental levels of Indian SCD patients, trait, and healthy controls (n = 10 per group) via inductively coupled plasma mass spectrometry. In addition, erythrocyte metabolomics of Indian SCD and healthy (n = 5 per group) was carried out using liquid chromatography-mass spectrometry. Followed by assessment of antioxidant defense enzymes namely glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma of Indian SCD patients (n = 31) compared with trait (n = 10) and healthy (n = 10). In SCD plasma an elevated plasma 24 Mg, 44Ca, 66Zn, 208Pb, 39K and reduced 57Fe, 77Se, and 85Rb levels indicated higher hemolysis and anemia. Erythrocyte metabolome of SCD patients clustered separately from healthy revealed 135 significantly deregulated metabolic features, including trimethyllysine, pyroglutamate, glutathione, aminolevulinate, and d-glutamine, indicating oxidative stress and membrane fragility. Repressed GR, SOD, and CAT activities were observed in SCD patients of which GR and CAT activities did not change under hypoxia. These findings lead to the hypothesis that SCD-associated metabolic deregulations and a shift to ATP-consuming aberrant γ-glutamyl cycle leads to anemia, dehydration, oxidative stress, and hemolysis driving the biomechanical pathophysiology of erythrocyte of SCD patients.

BACKGROUND: Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative.
METHODS: We used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC-transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012-2018.
RESULTS: There were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC-transfused patients had 1 (~46%) or 2-5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte-reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities.
CONCLUSIONS: ISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities.

Aging is characterized by increased oxidation and reduced efficiency of cytoprotective mechanisms. Nuclear factor erythroid-2-related factor (Nrf2) is a key transcription factor, controlling the expression of multiple antioxidant proteins. Here, we show that Nrf2-/- mice displayed an age-dependent anemia, due to the combined contributions of reduced red cell lifespan and ineffective erythropoiesis, suggesting a role of Nrf2 in erythroid biology during aging. Mechanistically, we found that the expression of antioxidants during aging is mediated by activation of Nrf2 function by peroxiredoxin-2. The absence of Nrf2 resulted in persistent oxidation and overactivation of adaptive systems such as the unfolded protein response (UPR) system and autophagy in Nrf2-/- mouse erythroblasts. As Nrf2 is involved in the expression of autophagy-related proteins such as autophagy-related protein (Atg) 4-5 and p62, we found impairment of late phase of autophagy in Nrf2-/- mouse erythroblasts. The overactivation of the UPR system and impaired autophagy drove apoptosis of Nrf2-/- mouse erythroblasts via caspase-3 activation. As a proof of concept for the role of oxidation, we treated Nrf2-/- mice with astaxanthin, an antioxidant, in the form of poly (lactic-co-glycolic acid) (PLGA)-loaded nanoparticles (ATS-NPs) to improve its bioavailability. ATS-NPs ameliorated the age-dependent anemia and decreased ineffective erythropoiesis in Nrf2-/- mice. In summary, we propose that Nrf2 plays a key role in limiting age-related oxidation, ensuring erythroid maturation and growth during aging.

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Each unit of red blood cells (RBCs) produced represents a significant cost to the healthcare system. Unnecessary blood wastage should be minimized. In clinical settings, alterations to blood component bags after issue from the protected setting of the blood bank include pen markings, and those that are exposed to an infectious environment require surface disinfecting. These units may be discarded due to unclear effects on RBC quality. In this study, we investigate whether pen markings or surface disinfection negatively affects the quality of packed RBCs and whether pen ink diffuses through the blood bag.
RBC bags were marked with pens (water, oil, or alcohol-based) or subjected to surface disinfection (ethanol, hydrogen peroxide [Preempt wipes], or benzalkonium chloride-based wipes [CaviWipes]) and sampled 24 h after applying the treatment and at day 42 post collection (n = 3 for each condition). The samples were analyzed for RBC in vitro quality markers. The presence of any ink in the RBC bags was investigated using mass spectrometry (n = 2).
Data from 24 h and day 42 time points indicated no differences in RBC count, mean corpuscular volume, morphology, deformability, potassium content, or hemolysis for either pen markings or disinfectants when compared with their untreated controls (p > .05). No trace of ink was detected inside the bag.
RBC units marked with ballpoint, gel, or Sharpie pens do not suffer a loss of in vitro quality, nor do RBC units which have been surface disinfected with 70% ethanol, Preempt wipes or CaviWipes.

Several syndromes affecting the red cell that mimic those induced by germline mutations may result from a somatic mutation that accompanies a myeloid malignancy. These syndromes are most notable in cases of myelodysplastic syndrome, but they are not limited to any one category of myeloid neoplasm. Their occurrence in males exceed the male predominance that is evident in myeloid neoplasms. The syndromes include disorders of globin chain synthesis (α- and β-thalassemia), heme synthesis (erythropoietic porphyria and erythropoietic uroporphyria), red cell membrane structure (elliptocytosis and spherocytosis), red cell enzyme activity (pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency) and lowered expression of red cell ABO blood group antigens. This historical review describes the path to uncovering these acquired syndromes and their causal somatic mutations, where known. These syndromes often go unrecognized because of the dominant concern of the primary neoplasm. They may add to the healthcare needs of the patient.

BACKGROUND: We recently introduced a policy to use O positive red cells in emergency transfusions for males >16 years of age and females >50 years of age. Here, we investigate changes in emergency transfusion practice and rates of red cell alloimmunization with the use of O positive blood for emergency transfusion.
METHODS: State-wide retrospective review of emergency transfusions between June 2020 and June 2021. The laboratory information system and patient medical records were used to collect demographic details, indications for transfusion, usage of O positive and O negative blood and rates of alloimmunization.
RESULTS: There were 2354 red cell units transfused to 1013 patients (male = 59%, average age = 53 years) during the 12-month period. O positive units accounted for 46.9% (1103 units) of emergency transfusions. However, 726 (30.8%) O negative units were transfused to patients without a mandatory indication for O negative blood. Twenty-eight patients (2.9%) had a red cell alloantibody prior to transfusion including anti-E (n = 10), anti-D (n = 4), and anti-K (n = 4). One patient with prior anti-D had mild delayed hemolysis. There were 19 patients (4.3%, median follow-up 22 days) who developed a red cell alloantibody after emergency transfusion and include anti-E (n = 10), anti-D (n = 7), and anti-C (n = 5).
CONCLUSIONS: The use of O positive blood for emergency transfusion has saved 1103 O negative red cell units with no detriment to patient outcome. There remains potential to optimize use of O positive blood in emergency transfusion and to understand red cell alloimmunization rates in a prospective fashion.

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