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Summary: 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. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chemical and carcinogenic risk in workplace are linked to an increase of the incidence of cancer in exposed workers. The aim of this observational study was to identify an association between exposure to chemical risk and changes in hematochemical parameters of workers exposed. Methods: The study examined blood count parameters performed on 4523 employees of Sapienza University of Rome from September 2019 to February 2020. A total of 1402 workers in research laboratories, exposed to chemical risk and carcinogens, was compared with a cohort of 3121 blood donors, in apparently good health, matched for age, sex, and period of blood collection. Results: Multivariate analysis demonstrated acrylamide is the most frequently associated chemical with significant changes between the groups. It is related to an increase in monocytes and MPV, a reduction of lymphocytes, platelets, and red series values, while MCH remained unchanged. Formaldehyde reveals the same changes as acrylamide, with the exception of the percentage of lymphocytes, red blood cells, and HB, which remain unchanged. Other chemicals and carcinogens show variations for few blood count parameters. Conclusions: The present study found out a significant change in blood count values in workers exposed to acrylamide and formaldehyde. It also showed an increase in the mean monocyte value in employees exposed to carcinogenic risk, compared to non-exposed, with the exception of Trypan Blue. The implementation of efficient health surveillance remains of critical importance. These data should be compared with those from follow-up studies. [ABSTRACT FROM AUTHOR]

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; 205:1188‐1196 [ABSTRACT FROM AUTHOR]

The article discusses the use of predeposit autologous donation (PAD) in transfusion medicine. It highlights that PAD should only be used for patients with rare blood groups or multiple blood group antibodies where compatible allogeneic blood is difficult to obtain. The article also addresses recent concerns about the COVID-19 vaccination status of donors and emphasizes that PAD is not recommended for conscientious objections to donor blood. Preoperative autologous donation (PAD) is no longer recommended in obstetric practice due to the risks and potential complications involved. The article mentions various risks and concerns associated with PAD, such as errors in labeling and storage, donor anemia, wastage rates, and the need for fixed timings. It suggests alternative options like cell salvage and tranexamic acid. The guidelines recommend patient counseling, involvement of stakeholders, and adherence to blood regulations. Overall, PAD is rarely appropriate and should be carefully evaluated on a case-by-case basis. [Extracted from the article]

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. Discussion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Study Design and Methods: 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). Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

This article provides a review of studies examining the impact of transfusing older red blood cells (RBCs) on patient outcomes. The findings suggest that there is no significant association between RBC age and increased mortality or multi-organ dysfunction. However, there is some evidence of a modest association between RBCs stored for 35 days or more and increased mortality in cardiovascular acute care patients. The article acknowledges that more research is needed to establish the safety of RBCs near expiration and highlights the heterogeneity of the literature on this topic. Overall, current evidence suggests that RBC storage limits of up to 42 days are generally safe, but further investigation is required. [Extracted from the article]

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. Study Design and 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). Discussion: 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. [ABSTRACT FROM AUTHOR]

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.

Iron is a primary component of the human body and exerts many functions, mainly concerning red cells and the immune system. In addition, there is evidence that iron-deficiency anemia is associated with allergic diseases. Type 2 inflammation characterizes allergic diseases. Peripheral eosinophils are a reliable biomarker for type 2 inflammation. Therefore, the present study investigated the possible relationship between iron metabolism and peripheral eosinophils in a large population. Eosinophils also play important roles in immune and tissue homeostasis. A growing body of data suggests tissue eosinophils represent a plastic and heterogeneous population of functional sub-phenotypes, shaped by environmental (systemic and local) factors. The retrospective study included 2,795 subjects who were afferent to the Clinical Chemistry Analysis Laboratory during the year 2022. Men had higher peripheral eosinophil count than women (p<0.001). Furthermore, stratifications for sex, eosinophil, and hemoglobin cut-offs showed that men had more eosinophil counts than women. However, there was no correlation between iron biomarkers and peripheral eosinophils. The present study did not demonstrate a clear relationship between iron deficiency and peripheral eosinophil count. Even if this large population may include allergic subjects and patients with different diseases, it seems that iron does not directly affect eosinophil count. [ABSTRACT FROM AUTHOR]

BackgroundCentral nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan.ObjectiveThese evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD.MethodsThe Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations.ResultsThe panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings.ConclusionsThree of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

Sea urchins have emerged as an important source of bioactive compounds with anti-inflammatory and antioxidant properties relevant to human health. Since inflammation is a crucial pathogenic process in the development and progression of atherosclerosis, we here assessed the potential anti-inflammatory and vasculoprotective effects of coelomic red-cell methanolic extract of the black sea urchin Arbacia lixula in an in vitro model of endothelial cell dysfunction. Human microvascular endothelial cells (HMEC-1) were pretreated with A. lixula red-cell extract (10 and 100 μg/mL) before exposure to the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The extract was non-toxic after 24 h cell treatment and was characterized by antioxidant power and phenol content. The TNF-α-stimulated expression of adhesion molecules (VCAM-1, ICAM-1) and cytokines/chemokines (MCP-1, CCL-5, IL-6, IL-8, M-CSF) was significantly attenuated by A. lixula red-cell extract. This was functionally accompanied by a reduction in monocyte adhesion and chemotaxis towards activated endothelial cells. At the molecular level, the tested extract significantly counteracted the TNF-α-stimulated activation of the pro-inflammatory transcription factor NF-κB. These results provide evidence of potential anti-atherosclerotic properties of A. lixula red-cell extract, and open avenues in the discovery and development of dietary supplements and/or drugs for the prevention or treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Iron is a primary component of the human body and exerts many functions, mainly concerning red cells and the immune system. In addition, there is evidence that iron-deficiency anemia is associated with allergic diseases. Type 2 inflammation characterizes allergic diseases. Peripheral eosinophils are a reliable biomarker for type 2 inflammation. Therefore, the present study investigated the possible relationship between iron metabolism and peripheral eosinophils in a large population. Eosinophils also play important roles in immune and tissue homeostasis. A growing body of data suggests tissue eosinophils represent a plastic and heterogeneous population of functional sub-phenotypes, shaped by environmental (systemic and local) factors. The retrospective study included 2,795 subjects who were afferent to the Clinical Chemistry Analysis Laboratory during the year 2022. Men had higher peripheral eosinophil count than women (p

Background: Red cell transfusion is indicated to increase the oxygen delivering capacity and it cannot be replaced by any pharmacological agent. Although blood transfusion is generally safe, adverse effects can occur; hence, benefits must always overweigh risks of transfusion before decision to transfuse is made. Information about the aims of transfusion, benefits and risks of transfusion, must be explained to the patient and written consent must be obtained. Objective: To assess the awareness about blood transfusion among red cell recipients. Materials and Methods: This prospective descriptive study was carried out at a tertiary care hospital in Sri Lanka. Red cell recipients were questioned about the transfusion episode after been transfused. Results: There were 252 patients in the study, 82 from surgical units and 170 from medical units. 37 (45.12%) patients from surgical units and 79 (46.47%) patients from medical units were explained about the transfusion, before they were being transfused. 66% of patients from surgical units and 55% from medical wards knew their blood group. 77% and 57% of patients were aware about the reason for transfusion in surgical and medical wards, respectively. Moreover, 39% of patients from surgical units and 35% of patients from medical units knew about transfusion transmitted infections. Conclusions: Awareness about the own blood group, reason for transfusion, benefits and risks of transfusion was significantly low in the study group. Therefore, patient education should be improved to understand the benefits and risks to the patient.

Abstract Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic requires tests to monitor antibody formation and prevalence. We detected SARS‐CoV‐2 antibodies using red cells coated by Kode technology with short peptides derived from the SARS‐CoV‐2 spike protein (SP). Such modified red cells, called C19‐kodecytes, can be used as reagent cells in any manual or automated column agglutination assay. We investigated the presence of SARS‐CoV‐2 antibodies in 130 samples from COVID‐19 convalescent plasma donors using standard manual technique, two FDA‐authorized enzyme‐linked immunosorbent assay (ELISA) assays and a virus neutralisation assay. The sensitivity of the C19‐kodecyte assay was 88%, comparable to the anti‐SP and anti‐nucleocapsid protein (NCP) ELISAs (86% and 83%) and the virus neutralisation assay (88%). The specificity of the C19‐kodecyte assay was 90% (anti‐SP 100% and anti‐NCP 97%). Likewise, 231 samples from 73 vaccinated individuals were tested with an automated analyser, and we monitored the appearance and persistence of SARS‐CoV‐2 antibodies. The C19‐kodecyte assay is a robust tool for SARS‐CoV‐2 antibody detection. Automated blood group analyser use enables large‐scale SARS‐CoV‐2 antibody testing for vaccination monitoring in population surveys.

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Introduction: Iron overloading disorders are associated with decreased bone mineral density. However, evidence on fracture risk is scarce. Therefore, we evaluated the risk of fracture associated with iron overload disorders, compared to matched controls., Methods: Using THIN, a Cegedim database of UK general practice data, we identified patients >18 years with elevated iron (ferritin value >1000 µg/L) or an eligible diagnosis code for iron overloading disorders between 2010-2022. The first date of elevated iron or a diagnosis code defined the index date for iron overload patients, who were matched with to up to 10 controls. Time-varying confounder adjusted Cox proportional hazard models estimated the hazard ratios (HRs) and 95% confidence intervals. Analyses were stratified by osteoporotic fracture site (hip, vertebral, humerus, forearm), evidence of elevated serum ferritin at baseline (ferritin >1000 µg/L), and sex., Results: We identified 20,264 eligible patients and 192,956 controls. Overall, there was a 55% increased risk of any fracture among iron overload patients (HR 1.55 [1.42-1.68]). Fracture risk was increased at all sites, with the highest risk observed for vertebral fractures (HR 1.97 [1.63-2.10]). Patients with ferritin >1000µg/L had a 91% increased risk of any fracture (HR 1.91 [1.73-2.16]) and a 2.5-fold increased risk of vertebral fractures (HR 2.51 [2.01-3.12]). There was no increased risk among patients without elevated serum ferritin at any site. Fracture risk was similar between sexes., Discussion: This large population-based cohort study found a 55% increased risk of fracture associated with iron overload. The risk was highest among patients with laboratory confirmed iron overload, highlighting the importance for clinicians to consider initiating osteoporosis therapy in patients with serum ferritin >1000 µg/L to minimize fracture risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Maintaining hematocrit (Hct) levels below 45% can reduce morbidity and mortality in patients with polycythemia vera (PV). A device that patients can use to self-monitor Hct levels could enable timely interventions if Hct levels increase above 45%, and could improve quality of life (QoL). This study evaluated the accuracy of the StatStrip Xpress® 2 LAC/Hb/Hct meter (Hb/Hct meter) when used by healthcare professionals (HCPs) or patients in clinical practice. Blood samples from 68 visits for 60 patients with PV or other hematological conditions were collected and analyzed by HCPs using a laboratory hematological analyzer, and by patients (self-test) and HCPs (professional test) using the Hb/Hct meter at two Swiss centers. Accuracy was assessed as the mean difference in readings between two users/methods (mdiff, 90% confidence interval; Spearman correlation [r]). The Hct values were similar between the professional test and analyzer (n = 66 comparisons, mdiff = 0.1% [−0.5 to 0.8]; r = 0.95, p < 0.001), the self-test and professional test (n = 62 comparisons, mdiff = −0.2% [−1.1 to 0.7]; r = 0.93, p < 0.001), and the self-test and analyzer (n = 63 comparisons, mdiff = 0.0% [−0.8 to 0.7]; r = 0.94, p < 0.001). The hemoglobin values across users/methods were also similar. Reporting their opinion on the Hb/Hct meter at visit 1, 100% of the patients found it easy to use, and 97% were willing to use it at home. Of the patients with PV, approximately 71% and 56%, respectively, stated that they would feel safer using a self-testing device, and that it would improve their QoL. These findings demonstrate the potential of the Hb/Hct meter for HCP and patient use in real-world settings. [ABSTRACT FROM AUTHOR]

Background and Objectives: D‐negative red cells are transfused to D‐negative females of childbearing potential (CBP) to prevent haemolytic disease of the foetus and newborn (HDFN). Transfusion of low‐titre group O whole blood (LTOWB) prehospital is gaining interest, to potentially improve clinical outcomes and for logistical benefits compared to standard of care. Enhanced donor selection requirements and reduced shelf‐life of LTOWB compared to red cells makes the provision of this product challenging. Materials and Methods: A universal policy change to the use of D‐positive LTOWB across England was modelled in terms of risk of three specific harms occurring: risk of haemolytic transfusion reaction now or in the future, and the risk of HDFN in future pregnancies for all recipients or D‐negative females of CBP. Results: The risk of any of the three harms occurring for all recipients was 1:14 × 103 transfusions (credibility interval [CI] 56 × 102–42 × 103) while for females of CBP it was 1:520 transfusions (CI 250–1700). The latter was dominated by HDFN risk, which would be expected to occur once every 5.7 years (CI 2.6–22.5). We estimated that a survival benefit of ≥1% using LTOWB would result in more life‐years gained than lost if D‐positive units were transfused exclusively. These risks would be lower, if D‐positive blood were only transfused when D‐negative units are unavailable. Conclusion: These data suggest that the risk of transfusing RhD‐positive blood is low in the prehospital setting and must be balanced against its potential benefits. [ABSTRACT FROM AUTHOR]

The erythrocyte sedimentation rate (ESR) is one of the oldest medical diagnostic tools. However, currently there is some debate on the structure formed by the cells during the sedimentation process. While the conventional view is that erythrocytes sediment as separate aggregates, others have suggested that they form a percolating gel, similar to other colloidal suspensions. However, visualization of aggregated erythrocytes, which would settle the question, has always been challenging. Direct methods usually study erythrocytes in 2D situations or low hematocrit (∼1%). Indirect methods, such as scattering or electric measurements, provide insight on the suspension evolution, but cannot directly discriminate between open or percolating structures. Here, we achieved a direct probing of the structures formed by erythrocytes in blood at stasis. We focused on blood samples at rest with controlled hematocrit of 45%, from healthy donors, and report observations from three different optical imaging techniques: direct light transmission through thin samples, two-photon microscopy and light-sheet microscopy. The three techniques, used in geometries with thickness from 150 μm to 3 mm, highlight that erythrocytes form a continuous network with characteristic cracks, i.e., a colloidal gel. The characteristic distance between the main cracks is of the order of ∼100 μm. A complete description of the structure then requires a field of view of the order of ∼1 mm, in order to obtain a statistically relevant number of structural elements. A quantitative analysis of the erythrocyte related processes and interactions during the sedimentation need a further refinement of the experimental set-ups. [ABSTRACT FROM AUTHOR]

Around 70 infectious agents are possible threats for blood safety.

The erythrocyte sedimentation rate (ESR) is one of the oldest medical diagnostic tools. However, currently there is some debate on the structure formed by the cells during the sedimentation process. While the conventional view is that erythrocytes sediment as separate aggregates, others have suggested that they form a percolating gel, similar to other colloidal suspensions. However, visualization of aggregated erythrocytes, which would settle the question, has always been challenging. Direct methods usually study erythrocytes in 2D situations or low hematocrit (∼1%). Indirect methods, such as scattering or electric measurements, provide insight on the suspension evolution, but cannot directly discriminate between open or percolating structures. Here, we achieved a direct probing of the structures formed by erythrocytes in blood at stasis. We focused on blood samples at rest with controlled hematocrit of 45%, from healthy donors, and report observations from three different optical imaging techniques: direct light transmission through thin samples, two-photon microscopy and light-sheet microscopy. The three techniques, used in geometries with thickness from 150 μm to 3 mm, highlight that erythrocytes form a continuous network with characteristic cracks, i.e., a colloidal gel. The characteristic distance between the main cracks is of the order of ∼100 μm. A complete description of the structure then requires a field of view of the order of ∼1 mm, in order to obtain a statistically relevant number of structural elements. A quantitative analysis of the erythrocyte related processes and interactions during the sedimentation need a further refinement of the experimental set-ups.

Background: Blood components are irradiated to inactivate lymphocytes to prevent transfusion‐associated graft versus host disease. As there are little data regarding the effects of X‐irradiation on red blood cell components (RBCs), the in vitro quality of stored red cells (standard, pediatric, washed, and intra‐uterine transfusion [IUT]) following X‐ or gamma‐irradiation was compared. Study design and methods: RBCs were pooled, split, and processed to produce standard (<14 days and < 5 days post‐collection), pediatric (<5 days post‐collection), washed (<14 days post‐collection), or IUT RBCs (<5 days post‐collection). Standard RBCs were either X‐ or gamma‐irradiated (n = 10 pairs). A further 10 replicates were prepared by pooling and splitting three matched RBCs (X‐, gamma‐, and non‐irradiated). All other RBCs were either X‐ or gamma‐irradiated (n = 20 pairs). Red cell indices, hemolysis, potassium release, metabolism, microparticles, ATP, and 2,3‐DPG were measured pre‐irradiation and 6 h, 1, 2, 3, 7, 10, and 14 days post‐irradiation, depending on the component type. Data were analyzed using two‐way repeated measures ANOVA. Results: There were no significant differences in any in vitro quality measurements, with the exception of marginally higher potassium release in washed, IUT, and RBCs <5 days old (p <.0001) following X‐irradiation. Both irradiation types increased generation of microvesicles, particularly in components that were older at the time of irradiation or stored for longer post‐irradiation. Conclusion: X‐ and gamma‐irradiation have similar effects on the in vitro quality of RBCs, indicating that either technology is suitable for blood component irradiation. [ABSTRACT FROM AUTHOR]

Abstract Background It has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children. Methods We analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another—comparable—group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma. Results The gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features, and appeared to be linked by a complex network of inter-correlations involving the Aryl Hydrocarbon Receptor signaling pathway. In addition, when the study of inter-correlations within the expression pattern of these molecules was extended to include the healthy subjects, the intrinsic physiological relationships of the inflammatory/oxidative stress network emerged. Plasma levels of Prx2 and Prx5 were remarkably increased in ASD compared to healthy controls, while no significant differences were found in red cell Prx levels. Conclusions Previous findings reported elevated inflammatory cytokines in the plasma of ASD children, without clearly pointing to the presence of neuro-inflammation. On the other hand, the finding of microglia activation in autoptic specimens was clearly suggesting the presence of neuro-inflammation in ASD. Given the role of peroxiredoxins in the protection of brain cells against oxidative stress, the whole of our results, using peripheral data collected in living patients, support the involvement of neuro-inflammation in ASD, and generate a rational for neuro-inflammation as a possible therapeutic target and for plasma Prx5 as a novel indicator of ASD severity.

Hereditary spherocytosis (HS) is the commonest inherited red cell membrane disorder seen in clinical practice. Modern hematology analyzers generate newer parameters that can help in screening of HS. The present study focuses on the utility of red blood cell data generated by Advia-120 hematology analyzer as a screening tool for patients with HS. Blood samples from 21 patients with HS were analyzed on Advia-120 (Technicon H*1 series) analyzer. The percentage of hyperchromic cells and hyperchromic and hemoglobin concentration variance flags along with the RBC cytogram were studied. A control group of 50 healthy individuals and 50 patients with other hematological disorders was also studied. Osmotic fragility test was done in all patients with suspected HS. All hematological parameters including percentage of hyperchromic red cells were compared between the study group, healthy controls, and other hematological disorders. Twenty of the 21 patients with HS were anemic. Peripheral blood smear in all patients showed variable numbers of spherocytes (5–50%). Osmotic fragility test was positive in all patients. The mean percentage of hyperchromic cells in patients with HS-18.2 ± 13.0% was significantly higher (p < 0.0001) than that seen in the control group and in patients with other hematological disorders. Hyperchromic RBC > 6% showed a sensitivity of 100% and specificity of 99% for the diagnosis of HS. All patients showed flagging for hyperchromic cells. The RBC cytograms in all 21 patients showed significant number of RBCs plotted in the hyperchromic zone. The percentage of hyperchromic cells, hyperchromic cell flagging, and RBC cytogram pattern generated by Advia-120 hematology analyzer are useful tools in the screening of patients with suspected HS. [ABSTRACT FROM AUTHOR]

Anaemia is a common finding in patients presenting for major elective surgery and is associated with poor outcomes including death and complications. Iron deficiency is the leading cause of perioperative anaemia. Intravenous (i.v.) iron is considered to be an effective and safe treatment for iron deficiency anaemia and is recommended by expert opinion for treatment of preoperative anaemia, although evidence from clinical trials is lacking. The PREVENTT trial was a large multicentre trial investigating the effects of i.v. iron on red cell transfusion, death, complications and quality of life in 487 patients undergoing major abdominal surgery. The principal finding of this multicentre randomised placebo controlled trial was that there was no difference in the co-primary outcomes of blood transfusion or death, or the number of transfusion episodes, within 30 days after surgery, in patients that received preoperative i.v. iron therapy compared to placebo. The major inferential differences in this independent discussion relate to the limitations of the PREVENTT trial and its implications for future practice. Although PREVENTT represents the best evidence available to guide perioperative use of i.v. iron, it is likely that the study was underpowered. In the context of already widespread adoption of preoperative i.v. iron therapy, many clinicians may have felt they lacked equipoise. In light of the PREVENTT study routine use of i.v. iron in patients undergoing elective abdominal surgery cannot be recommended. Further research should define the optimum red cell transfusion strategy for patients undergoing surgery and idenify other surgical groups who may benefit from this intervention. [ABSTRACT FROM AUTHOR]

Background & objectives Red cell concentrates (RCCs) must comply with applicable quality control (QC) standards to achieve the desired therapeutic effect in the recipient. In this study, we assessed the effect of change in the component preparation process on the quality of RCCs and their compliance with different QC standards. Methods A retrospective analysis of data for QC testing of RCCs over a period of 10 years, (from 2009 to 2019), was undertaken. QC testing parameters [volume, haematocrit (Hct), haemoglobin (Hb) content, white blood cell (WBC) content and percentage (%) haemolysis] were used to assess compliance with three national and three international QC standards. Linear regression analysis was done to assess the influence of donor variables. Results Data from 5,218 RCC units was included in the analysis. A majority (>50%) of RCCs prepared did not meet the three national QC standards either for volume or for Hct. The criteria for volume, Hct and Hb content, as defined in different international standards, were fulfilled by a majority (>75%) of RCCs evaluated. RCCs prepared by the buffy coat method had overall better compliance with QC standards compared to the platelet-rich plasma (PRP) method. The method of component preparation was found to influence Hb content, WBC content and percentage haemolysis. Male gender was associated with better Hb content. Interpretation & conclusions RCC prepared at our centre was found to have better compliance with international QC criteria compared to national standards. There is a need to reconsider the current national QC criteria for red cells with due consideration to the volume of whole blood collected and the method used for RCC preparation.

Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expressed. Previously, we report that Fyn is important in stress erythropoiesis. Here, we show that in red cells Fyn specifically stimulates G6PD activity, resulting in a 3-fold increase enzyme catalytic activity (kcat) by phosphorylating tyrosine (Tyr)-401. We found Tyr-401 on G6PD as functional target of Fyn in normal human red blood cells (RBC), being undetectable in G6PD deficient RBCs (G6PD-Mediterranean and G6PD-Genova). Indeed, Tyr-401 is located to a region of the G6PD molecule critical for the formation of the enzymatically active dimer. Amino acid replacements in this region are mostly associated with a chronic hemolysis phenotype. Using mutagenesis approach, we demonstrated that the phosphorylation status of Tyr401 modulates the interaction of G6PD with G6P and stabilizes G6PD in a catalytically more efficient conformation. RBCs from Fyn-/−mice are defective in G6PD activity, resulting in increased susceptibility to primaquine-induced intravascular hemolysis. This negatively affected the recycling of reduced Prx2 in response to oxidative stress, indicating that defective G6PD phosphorylation impairs defense against oxidation. In human RBCs, we confirm the involvement of the thioredoxin/Prx2 system in the increase vulnerability of G6PD deficient RBCs to oxidation. In conclusion, our data suggest that Fyn is an oxidative radical sensor, and that Fyn-mediated Tyr-401 phosphorylation, by increasing G6PD activity, plays an important role in the physiology of RBCs. Failure of G6PD activation by this mechanism may be a major limiting factor in the ability of G6PD deficient RBCs to withstand oxidative stress.

The N-methyl-D-aspartate receptor (NMDAR) provides a pathway for glutamate-mediated inter-cellular communication, best known for its role in the brain but with multiple examples of functionality in non-neuronal cells. Data previously published by others and us provided ex vivo evidence that NMDARs regulate platelet and red blood cell (RBC) production. Here, we summarize what is known about these hematopoietic roles of the NMDAR. Types of NMDAR subunits expressed in megakaryocytes (platelet precursors) and erythroid cells are more commonly found in the developing rather than adult brain, suggesting trophic functions. Nevertheless, similar to their neuronal counterparts, hematopoietic NMDARs function as ion channels, and are permeable to calcium ions (Ca2+). Inhibitors that block open NMDAR (memantine and MK-801) interfere with megakaryocytic maturation and proplatelet formation in primary culture. The effect on proplatelet formation appears to involve Ca2+ influx-dependent regulation of the cytoskeletal remodeling. In contrast to normal megakaryocytes, NMDAR effects in leukemic Meg-01 cells are diverted away from differentiation to increase proliferation. NMDAR hypofunction triggers differentiation of Meg-01 cells with the bias toward erythropoiesis. The underlying mechanism involves changes in the intracellular Ca2+ homeostasis, cell stress pathways, and hematopoietic transcription factors that upon NMDAR inhibition shift from the predominance of megakaryocytic toward erythroid regulators. This ability of NMDAR to balance both megakaryocytic and erythroid cell fates suggests receptor involvement at the level of a bipotential megakaryocyte-erythroid progenitor. In human erythroid precursors and circulating RBCs, NMDAR regulates intracellular Ca2+ homeostasis. NMDAR activity supports survival of early proerythroblasts, and in mature RBCs NMDARs impact cellular hydration state, hemoglobin oxygen affinity, and nitric oxide synthase activity. Overexcitation of NMDAR in mature RBCs leads to Ca2+ overload, K+ loss, RBC dehydration, and oxidative stress, which may contribute to the pathogenesis of sickle cell disease. In summary, there is growing evidence that glutamate-NMDAR signaling regulates megakaryocytic and erythroid cells at different stages of maturation, with some intriguing differences emerging in NMDAR expression and function between normal and diseased cells. NMDAR signaling may provide new therapeutic opportunities in hematological disease, but in vivo applicability needs to be confirmed.

The N -methyl-D-aspartate receptor (NMDAR) provides a pathway for glutamate-mediated inter-cellular communication, best known for its role in the brain but with multiple examples of functionality in non-neuronal cells. Data previously published by others and us provided ex vivo evidence that NMDARs regulate platelet and red blood cell (RBC) production. Here, we summarize what is known about these hematopoietic roles of the NMDAR. Types of NMDAR subunits expressed in megakaryocytes (platelet precursors) and erythroid cells are more commonly found in the developing rather than adult brain, suggesting trophic functions. Nevertheless, similar to their neuronal counterparts, hematopoietic NMDARs function as ion channels, and are permeable to calcium ions (Ca2+). Inhibitors that block open NMDAR (memantine and MK-801) interfere with megakaryocytic maturation and proplatelet formation in primary culture. The effect on proplatelet formation appears to involve Ca2+ influx-dependent regulation of the cytoskeletal remodeling. In contrast to normal megakaryocytes, NMDAR effects in leukemic Meg-01 cells are diverted away from differentiation to increase proliferation. NMDAR hypofunction triggers differentiation of Meg-01 cells with the bias toward erythropoiesis. The underlying mechanism involves changes in the intracellular Ca2+ homeostasis, cell stress pathways, and hematopoietic transcription factors that upon NMDAR inhibition shift from the predominance of megakaryocytic toward erythroid regulators. This ability of NMDAR to balance both megakaryocytic and erythroid cell fates suggests receptor involvement at the level of a bipotential megakaryocyte-erythroid progenitor. In human erythroid precursors and circulating RBCs, NMDAR regulates intracellular Ca2+ homeostasis. NMDAR activity supports survival of early proerythroblasts, and in mature RBCs NMDARs impact cellular hydration state, hemoglobin oxygen affinity, and nitric oxide synthase activity. Overexcitation of NMDAR in mature RBCs leads to Ca2+ overload, K+ loss, RBC dehydration, and oxidative stress, which may contribute to the pathogenesis of sickle cell disease. In summary, there is growing evidence that glutamate-NMDAR signaling regulates megakaryocytic and erythroid cells at different stages of maturation, with some intriguing differences emerging in NMDAR expression and function between normal and diseased cells. NMDAR signaling may provide new therapeutic opportunities in hematological disease, but in vivo applicability needs to be confirmed. [ABSTRACT FROM AUTHOR]

Summary: Optimal red cell transfusion support in myelodysplastic syndromes (MDS) has not been tested and established. The aim of this study was to demonstrate feasibility of recruitment and follow‐up in an outpatient setting with an exploratory assessment of quality of life (QoL) outcomes (EORTC QLQ‐C30 and EQ‐5D‐5L). We randomised MDS patients to standardised transfusion algorithms comparing current restrictive transfusion thresholds (80 g/l, to maintain haemoglobin 85–100 g/l) with liberal thresholds (105 g/l, maintaining 110–125 g/l). The primary outcomes were measures of compliance to transfusion thresholds. Altogether 38 patients were randomised (n = 20 restrictive; n = 18 liberal) from 12 participating sites in UK, Australia and New Zealand. The compliance proportion for the intention‐to‐treat population was 86% (95% confidence interval 75–94%) and 99% (95–100%) for restrictive and liberal arms respectively. Mean pre‐transfusion haemoglobin concentrations for restrictive and liberal arms were 80 g/l (SD6) and 97 g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm. Our findings support the feasibility and need for a definitive trial to evaluate the effect of different red cell transfusion thresholds on patient‐centred outcomes. [ABSTRACT FROM AUTHOR]

Introduction: In the French armed forces, the biological checkup required during the recruitment process comprises a urinalysis (urinary dipstick), a complete blood count (CBC), and measurement of serum levels of aspartate aminotransferase, alanine aminotransferase, fasting blood glucose, and creatinine. This study aimed to evaluate the benefits of this biological checkup and to determine the most relevant parameters.Materials and Methods: We conducted a monocentric retrospective study of all standardized and systematically conducted blood tests (CBC and measurement of aspartate aminotransferase, alanine aminotransferase, fasting blood glucose, and creatinine) over a 15-month period among 726 French Army recruits.Results: The population included mainly young males (85.4%, mean age 21.6 years). More than half (54.1%) of the blood tests had at least one abnormal parameter, most often concerning the CBC. Anemia occurred in 5.3% of the population and was mostly normocytic. Microcytosis was mostly not associated with anemia (72.3% of cases). Lymphopenia occurred in 20.1% of the population and was mostly mild. Eosinophilia was present in 5.1% of the population and was never severe. Thrombocytopenia occurred in 0.7% of the population and was never severe. Serum levels of aminotransferases were elevated in 8.1% of the population. Fasting plasma glucose averaged 84 mg/dL (SD: 0.07) ranging from 64 to 123 mg/dL, was abnormal in 0.4% of the population, and one case of diabetes was diagnosed. Serum creatinine concentration was elevated in 0.7% of the population.Conclusion: CBCs gave useful information but iron deficiency was common and insufficiently detected by this single analysis. Assessing aminotransferase levels without screening for viral hepatitis and systematic measurement of fasting plasma glucose levels did not appear to be efficient. In addition, the only interest in systematic measurement of creatinine serum levels was to obtain a reference level for long-term follow-up. In addition to the urinary dipstick, the systematic biological checkup at recruitment could be limited to a CBC with measurement of plasma ferritin levels and Hepatitis B virus serology, providing that any CBC abnormalities, in particular cytopenia, eosinophilia, and microcytosis, are systematically investigated. For a public health approach, systematic screening for other sexually transmitted infections could be proposed. [ABSTRACT FROM AUTHOR]

Immune haemolytic anaemia (IHA) is characterized by an increased breakdown of red blood cells (RBCs) due to allo- or auto-antibodies directed to RBC antigens with or without complement activation. Based on the nature of the antibodies, IHA can be divided in three main categories: autoimmune, drug-induced and alloimmune-mediated IHA. There is growing evidence that the innate immune system plays an important role in the pathogenesis of IHA. Complement-mediated haemolysis with the subsequent release of cell-free haemoglobin and cellfree haem resulting in the generation of reactive oxygen species and cytotoxicity as well as the production of anaphylatoxins induce a systemic inflammatory response, which contributes to morbidity and mortality in IHA. The natural plasma scavengers of cell-free haemoglobin and cell-free haem, haptoglobin and hemopexin, respectively, are depleted in cases of chronic or severe IHA. The inducible enzyme haem oxygenase 1 (HO-1) is an efficient cellular scavenger degrading haem into anti-inflammatory products to partially limit haemmediated oxidative damage in cases of saturated scavenging capacity. Complement-targeted therapy and the therapeutic replenishment of haptoglobin and hemopexin as well as the induction of HO-1 expression might be suitable targets in the treatment of IHA. [ABSTRACT FROM AUTHOR]

In recent years, there has been a concerted effort to improve our understanding of the quality and effectiveness of transfused blood components. The expanding use of large datasets built from electronic health records allows the investigation of potential benefits or adverse outcomes associated with transfusion therapy. Together with information regarding blood donor demographics and component collection and manufacturing, these datasets permit evaluation of associations between donor or component factors and transfusion recipient outcomes. Large linked 'vein-to-vein' datasets provide the power to study exposures relevant to transfusion efficacy and safety, many of which would not otherwise be amenable to study for practical or sample size reasons. Analyses of these large donor-component-recipient datasets allow for characterization of the populations under study and provide an evidence base for future clinical studies. Knowledge generated from linked analyses has the potential to change the way donors are selected and how components are processed, stored and allocated. However, unrecognized confounding and biased statistical methods continue to be limitations in the study of transfusion exposures and patient outcomes. Given these challenges, results of observational studies of blood donor demographics, storage age and transfusion practice have been conflicting. This review summarizes statistical and methodological challenges in analyses of linked blood donor, component and transfusion recipient outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Cation channels play an essential role in red blood cells (RBCs) ion homeostasis. One set of ion channels are the transient receptor potential channels of canonical type (TRPC channels). The abundance of these channels in primary erythroblasts, erythroid cell lines and RBCs was associated with an increase in intracellular Ca2+ upon stimulation with Erythropoietin (Epo). In contrast two independent studies on Epo-treated patients revealed diminished basal Ca2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet. Methods: To resolve the seemingly conflicting reports we challenged mature human and mouse RBCs of several genotypes with Epo and Prostaglandin E2 (PGE2) and recorded the intracellular Ca2+ content. Next Generation Sequencing was utilised to approach a molecular analysis of reticulocytes. Results/Conclusions: Our results allow concluding that Epo and PGE2 regulation of the Ca2+ homeostasis is distinctly different between murine and human RBCs and that changes in intracellular Ca2+ upon Epo treatment is a primary rather than a compensatory effect. In human RBCs, Epo itself has no effect on Ca2+ fluxes but inhibits the PGE2-induced Ca2+ entry. In murine mature RBCs functional evidence indicates TRPC4/C5 mediated Ca2+ entry activated by Epo whereas PGE2 leads to a TRPC independent Ca2+ entry.

Objectives: Type II heparin‐induced thrombocytopenia (HIT) is mediated by formation of antibodies to platelet factor 4 (PF4)‐heparin complexes. We evaluated anti–PF4‐heparin‐negative samples for the presence of additional anti‐platelet and anti‐red blood cell (RBC) antibodies using whole‐cell platelet/ RBC ELISAs we developed. Methods: Seventy‐three samples tested for anti–PF4‐heparin by ELISA were included: 62 tested negative, 9 tested positive, and 2 had equivocal results. Plasma specimens from healthy donors were used as controls. Results: 100% (9/9) anti–PF4‐positive samples had anti‐platelet antibodies detected by whole‐cell platelet ELISA. 42.2% (27/64) anti–PF4‐heparin‐negative samples were negative for anti‐platelet and anti‐RBC antibodies. 32.8% (21/64) negative samples showed reactivity to both platelets and RBC; 12.5% (8/64) negative samples were each reactive with either platelet or RBC ELISA, respectively. Additionally, two samples that tested equivocal by anti–PF4‐heparin ELISA had antibodies to both platelets and RBC by whole‐cell ELISA. Conclusions: Our study suggests that patients with thrombocytopenia testing negative for anti–PF4‐heparin may still harbor antibodies to platelets. However, additional research is needed to determine the significance of these antibodies. Nevertheless, these findings may encourage clinicians to further investigate patients with possible immune‐mediated etiologies of thrombocytopenia and anemia. [ABSTRACT FROM AUTHOR]

Background: Hemorrhage is a critical contributor to maternal morbidity but estimation of blood loss at delivery is frequently inaccurate. Due to this inaccuracy we sought to examine blood transfusion as a surrogate marker for morbidity in a large non-population based consecutive cohort. Methods: A retrospective analysis of prospectively gathered data was carried out at two university institutions serving a heterogeneous urban obstetric population from January to December 2016. Data were analyzed to determine whether individual characteristics were associated with perinatal transfusion. Hematological indices and requirement for other blood products were also characterized. Results: A total of 16,581 deliveries were recorded during the study and 1.7% (289/16,581) of the cohort required red cell transfusion. Those who received transfusion were more likely to be nulliparous, and to deliver <37 weeks' or >42 weeks' gestation. They were also more likely to have a macrosomic infant (birthweight >4 kg) and to have had a multiple pregnancy. Characteristics not associated with risk of transfusion included obesity [18% (52/289) vs. 15% (2445/16,292); P=0.18], and maternal age ≥35 years [28% (82/289) vs. 33% (5537/16,292); P=0.05]. Additional blood products were necessary in a small number of patients who received red cells. Conclusion: The rate of transfusion in a contemporary Irish cohort has risen compared with previous data. Several variables associated with transfusion are consistent with older studies but importantly; maternal obesity and advanced maternal age are not associated with transfusion. These data may encourage the investment of resources in a population previously considered low-risk and, following future studies, to improve strategies aimed at limiting blood transfusion. [ABSTRACT FROM AUTHOR]

Red cell transfusions are part of the routine supportive care following haematopoietic stem cell transplantation. There is increasing evidence from randomized controlled trials demonstrating that restrictive transfusion thresholds are equivalent to liberal thresholds in other patient populations. However, given the lack of patient‐centred outcomes and the longer transfusion support required for patients with haematologic malignancies, the results of these trials may not be generalizable to haematology–oncology patients. In the recently completed multicentre TRIST trial, we randomized 300 patients requiring an autologous or allogeneic haematopoietic stem cell transplantation to either a restrictive (haemoglobin threshold <70 g/l) or liberal (haemoglobin threshold <90 g/l) red cell transfusion strategy. Our primary outcome was health‐related quality of life measured by FACT‐BMT through day 100 post‐transplant. The median number of red cell units transfused was lower in the restrictive strategy group (2 vs. 4). The FACT‐BMT total score was higher at all time points for patients in the restrictive transfusion group including at baseline (109 vs. 103) and at 100 days (116·3 vs. 109·2). After adjustment for baseline, the FACT‐BMT score at day 100 in the restrictive group was statistically non‐inferior to the liberal group (P < 0·0001). There were no significant differences between the two groups for any other clinical outcomes. Based on the results of the TRIST trial, a restrictive haemoglobin threshold of 70 g/l should become standard practice in haematopoietic stem cell transplant patients, and, given the lack of other clinical studies, all other haematology–oncology inpatients. [ABSTRACT FROM AUTHOR]

Nineteen reports of 41 cases of acquired red cell elliptocytosis associated with a chronic myeloid neoplasm are described. Although the majority of cases have an abnormality of the long arm of chromosome 20, del(q20), several cases do not. Moreover, in one case a specific qualitative abnormality of red cell protein band 4.1(4.1R) was reported; however, several subsequent cases could find no abnormality of a red cell membrane protein or found a different abnormality, usually quantitative. Thus, this striking red cell phenotypic feature, acquired elliptocytosis, seen in myelodysplastic syndrome and other chronic myeloproliferative diseases, closely simulating the red cell phenotype of hereditary elliptocytosis, has an unexplained genetic basis, presumably as the result of an acquired mutation(s) in some chronic myeloid neoplasms. [ABSTRACT FROM AUTHOR]

The dynamic coordination between kinases and phosphatases is crucial for cell homeostasis, in response to different stresses. The functional connection between oxidation and the intracellular signaling machinery still remains to be investigated. In the last decade, several studies have highlighted the role of reactive oxygen species (ROS) as modulators directly targeting kinases, phosphatases, and downstream modulators, or indirectly acting on cysteine residues on kinases/phosphatases resulting in protein conformational changes with modulation of intracellular signaling pathway(s). Translational studies have revealed the important link between oxidation and signal transduction pathways in hematological disorders. The intricate nature of intracellular signal transduction mechanisms, based on the generation of complex networks of different types of signaling proteins, revealed the novel and important role of phosphatases together with kinases in disease mechanisms. Thus, therapeutic approaches to abnormal signal transduction pathways should consider either inhibition of overactivated/accumulated kinases or homeostatic signaling resetting through the activation of phosphatases. This review discusses the progress in the knowledge of the interplay between oxidation and cell signaling, involving phosphatase/kinase systems in models of globally distributed hematological disorders.

The expression of blood group antigens varies across human populations and geographical regions due to natural selection and the influence of environment factors and disease. The red cell membrane is host to numerous surface antigens which are able to influence susceptibility to disease, by acting as receptors for pathogens, or by influencing the immune response. Investigations have shown that Human Immunodeficiency Virus (HIV) can bind and gain entry into erythrocytes, and therefore it is hypothesized that blood groups could play a role in this process. The ABO blood group has been well studied. However, its role in HIV susceptibility remains controversial, while other blood group antigens, and the secretor status of individuals, have been implicated. The Duffy antigen is a chemokine receptor that is important in the inflammatory response. Those who lack this antigen, and type as Duffy null, could therefore be susceptible to HIV infection, especially if associated with neutropenia. Other antigens including those in the Rh, Lutheran and OK blood group systems have all been shown to interact with HIV. More recently, experiments show that cells which overexpress the Pk antigen appear to be protected against infection. These reports all demonstrate that red cell antigens interact and influence HIV infection. However, as the red cell membrane is complex and the pathogenesis of HIV multi-factorial, the role of blood group antigens cannot be studied in isolation.