Therapeutic plasma exchange (PEX) has shown potential in improving transplant-free survival in acute liver failure (ALF) however the mechanism of action is not understood. This exploratory study aimed to elucidate the circulating proteomic changes associated with PEX in ALF to provide insight into mechanisms underlying the benefit of this therapy.

Red blood cell (RBC) transfusions carry risks, and the mechanisms mediating adverse transfusion outcomes are not fully understood. This review explores the impact of donor sex and donor-recipient sex mismatch on RBC characteristics and transfusion outcomes. Females, at least those in their reproductive age, have a higher proportion of young RBCs in the circulation when compared to males, associated with higher post transfusion recovery. Also, female RBCs exhibit a greater resilience to the storage lesion, with lower hemolysis rates and better rheologic properties. Despite these qualities, transfusion of female RBCs may be associated with adverse transfusion outcomes, such as pulmonary injury, increased mortality, and immunomodulatory effects, which may differ depending on the sex of the recipient, although not all observations are consistent. As a potential mechanism, the presence of immature RBCs, especially reticulocytes, in transfused blood is associated with immunomodulatory effects. Reticulocytes contain residual cellular components which can interact with surrounding blood cells and endothelial cells, in particular in neonates and cancer patients. Understanding the influence of donor sex and RBC age-subpopulation on RBC quality, and investigating the risks and benefits of immature RBCs in transfusions, offers opportunities for optimizing transfusion practices.

Transfusion of bacterially contaminated platelets may cause life threatening sepsis in the recipients. Cost of platelet screening is a major challenge for low middle income countries (LMICs). In this study, we evaluated the frequency of bacterial contamination in the platelet units (PUs) and the outcome of transfusing such platelets to the patients in a single institute at Pakistan.

Understanding red blood cell (RBC) subpopulations is crucial for comprehending donor variability and enhancing transfusion outcomes. This review highlights the significance of RBC subpopulations, focusing on the properties of biologically young and old RBCs and underscores how donor variability impacts transfusion outcomes. The role of senescent RBCs in adverse transfusion reactions and the emerging significance of circulating erythroid cells (CECs) is discussed. RBC aging and the role of oxidative stress and aging mechanisms is highlighted. Changes in RBC flexibility, calcium homeostasis, band 3 protein modifications, membrane microvesiculation, 2,3-diphosphoglycerate (2,3-DPG) levels, and immunological markers like CD47 and CD55 contribute to RBC clearance and erythrophagocytosis. Also, methods of characterizing / separating of biologically young and old RBC subpopulations is introduced. This review emphasizes the importance of RBC subpopulations in understanding donor variability and improving transfusion outcomes.

Whole blood donors who donate more frequency are more likely to develop iron deficiency, which could potentially affect the quality of the red blood cell (RBC) components during storage. Additional donor factors such as sex, age at donation, donor body mass index (BMI), as well as the manufacturing method could also affect RBC component quality, particularly haemolysis. The aim of this study was to examine the relationship between donation frequency, donor ferritin levels and BMI status on an extensive set of RBC characteristics in vitro, during storage at 2-6 °C for 42 days. A whole blood donation was collected from 787 Australian blood donors, held overnight, before top-and-bottom separation to produce RBC components. RBC components were tested using a panel of in vitro assays. Serum ferritin was tested from a sample taken at the time of donation, and donor demographic data was collected. Haemolysis in RBC components was not found to be associated with donation frequency. Increased red cell haemolysis, lactate concentration, extracellular potassium and RBC-derived microparticle numbers were significantly associated with a high BMI in male donors. There was also a trend towards increased red cell haemolysis in donors with ferritin concentrations in the upper range. Our findings indicate that although older male donors with potentially higher BMI are able to donate whole blood quite frequently, the resultant RBC components may have poorer in vitro quality.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse.

Clinical characteristics of blood donors may affect short- and long-term outcomes of transfusion recipients. The impact of donor sex and age on recipient outcomes have not yielded consistent results in observational studies. One recently published randomized controlled trial (iTADS) addressing the impact of donor sex on recipient outcomes noted no differences between a female versus male transfusion strategy; a second Canadian multicenter trial has just been funded. Other donor characteristics - including pregnancy history, smoking status, obesity, and chronic illnesses - remain incompletely explored. More robust clinical studies with vein-to-vein capabilities are needed to understand the complex interplay between donors and recipients.

The use of immune checkpoint inhibitors (ICIs) in individuals with a history of solid organ transplantation is fraught with the emergence of solid organ transplantation rejection (SOTR). The current recommendations for the management of SOTRs secondary to ICI include the use of high-dose steroids along with the escalation of immunosuppressive therapy. Therapeutic Plasma Exchange (TPE) has been described to be effective in managing various immune-related toxicities, however, the data for using TPE in the setting of acute SOTRs induced by ICIs are limited. Herein, we describe the successful use of TPE in a patient with a history of bilateral lung transplantation who developed an episode of mixed acute cellular and antibody-mediated lung transplant rejection after a single dose of PD-1 inhibitor Pembrolizumab for the treatment of underlying melanoma.

The performance assessment of quantitative measurements is predominantly based on evaluating Total Analytical Error (TAE). This evaluation encompasses several key objectives critical to ensuring accurate, reliable, and clinically relevant test results. Traditional parametric methods often fall short due to data normality assumptions in the performance assessment of in vitro diagnostic medical devices (IVD-MDs). This study presents a non-parametric approach to estimating and evaluating the TAE in transfusion medicine, aiming to enhance the reliability and patient safety of IVD-MDs. A protocol to estimate TAE over diverse data distributions is suggested, employing a robust statistical definition and comparative measurement procedures. Results from 200 samples indicate that non-parametric methods provided a more accurate reflection of TAE. The findings assert that non-parametric TAE estimation is vital for ensuring the 'fitness for purpose' of clinical tests in transfusion medicine, directly impacting post-transfusion outcomes and patient care. The study concludes that adopting non-parametric methods in transfusion services can significantly improve test accuracy, aligning with the highest laboratory practice standards.

Granulocyte transfusions (GTx) combat infections in neutropenic patients. However, immune-mediated off-target effects in transplant settings are unknown. Between January 2020 and December 2021, all transplants that used GTx during the peri-transplant period were analysed. Engraftment, infections, and days to clearance were retrieved from clinical records. Overall survival is compared with the mean total PMN count and the different products. Pooled buffy coat was used in 110 patients (98 %), of which 38 (34 %) additionally received an apheresed product. The median days of GTx was 4. The median bags pooled to prepare a single buffy coat product was 4. The mean total PMN count was 0.98 × 10/ L granulocytes per pooled buffy coat and 1.93 × 10/L granulocytes per apheresis product. A higher PMN count (>1 × 10/L) was achieved in 48 % with pooled buffy coat versus 85 % with apheresis. Respiratory worsening occurred in 39 % receiving GTx. All patients who received granulocytes had engrafted with a median time of 14 days for neutrophil and 20 days for platelet engraftment. Blood cultures cleared in 81 %, whereas only 28 % cleared other cultures. Fungal pneumonia cleared in 25 %, and invasive fungal sinusitis or otitis cleared in 50 %. Overall survival was 47 %, non-significantly higher (57 % vs 39 %, P = 0.1) with a higher PMN dose. The pooled buffy coat is an affordable alternative to apheresis for an effective PMN dose. Ease of availability and low cost of pooled buffy coat, with comparable overall survival points toward a safe and efficacious product, in the peri-transplant period.

Annexin A1, a protein released by neutrophils, is a potent regulator of inflammation in the intact form, but loses this activity when cleaved. The presence of autoantibodies to this protein can impact its function. An immunoassay, developed to measure autoantibodies to Annexin A1 in plasma or serum, has been developed and performances are reported. The cut-off for the positive range is determined from the mean value and standard deviations measured in a healthy group. Anti-Annexin A1 autoantibodies were then tested in hospitalized COVID-19 patients, at baseline or at any time during hospitalization. Sixty-one out of 379 patients tested positive for at least one isotype, IgG, IgA, or IgM. Few patients presented with only 1 isotype (2 G, 12 A, 16 M), but the combination of 2 isotypes was observed in many of them, and 3 expressed the 3 isotypes all together. Some association was noted between the presence of these autoantibodies and the development of thrombosis or admission in Intensive Care Units. The specific clinical complication risk associated to each isotype is yet to be established as our study was mainly transversal. Complementary studies are required to better evaluate the diagnostic or prognostic values of the anti-Annexin A1 autoantibodies, which have already been reported in various clinical situations. They could potentially reduce the anti-inflammatory regulation potential of Annexin A1, a mechanism which could contribute to disease evolution and worsening.

Transfusion of packed red blood cell (RBCs) saves millions of lives yearly worldwide, making packed RBCs the most commonly administered drug in hospitals after vaccines. However, not all blood units are created equal. By examining blood products as they age in blood banks, transfusion scientists are gaining insights into the intricacies of human chemical individuality as regulated by biological factors (such as sex, age, and body mass index), genetic and non-genetic factors like environmental, dietary, and other exposures. Here, we review recent literature on this topic, with an emphasis on studies linking genetic traits to the metabolic heterogeneity of blood products, the hemolytic propensity of stored RBCs, and transfusion outcomes in both healthy autologous and non-autologous patients requiring transfusion. Given the role of RBCs as a simplified model of eukaryotic cells, and RBC storage as a medically relevant application modeling erythrocyte responses to oxidant stress, these insights have the potential not only to guide the development of precision transfusion strategies, but also to identify novel mechanisms of RBC metabolic regulation relevant to responses to hypoxia and oxidant stress in human (patho)physiology.

Genetic mutations in genes regulating plasma testosterone in men may interfere with effective erythropoiesis, and may result in red blood cell (RBC) dysfunction and hemolysis. The aim of this study was to identify genetic polymorphisms in male donors that regulate plasma testosterone and impact RBC survival in cold storage and after transfusion. We evaluated nine single nucleotide polymorphisms (SNPs) previously reported to be associated with circulating testosterone in male plasma. These SNPs were linked with donor-component-recipient databases (NIH REDS program) to determine SNP associations with donor RBC hematological indices, osmotic and oxidative hemolysis, and RBC transfusion effectiveness defined as adjusted hemoglobin increments (delta hemoglobin, ΔHb) following a single RBC unit transfusion. Four of the nine testosterone SNPs were located on the X chromosome, of which two (rs7057002, rs73629199) were significantly associated with reduced hemoglobin increments (0.2 and 0.3 g/dL, respectively) compared with reference alleles in transfused recipients. Seven of the nine testosterone SNPs were associated with significant changes in RBC susceptibility to osmotic hemolysis including a missense mutation in the major plasma carrier of testosterone (SHBG, rs6259), and four SNPs with changes in oxidative hemolysis. Four SNPs were associated with decreased RBC count, hemoglobin, and hematocrit. Ancestry/ethnicity-specific (African and Hispanic) associations were observed between two SNPs (rs7057002, rs7879462) and oxidative hemolysis. Genetic determinants of plasma testosterone in male donors significantly impact the quality and transfusion effectiveness of cold stored RBCs. Testosterone SNPs associated with decreased RBC transfusion effectiveness may have clinical implications and warrant further revaluation.

Bacterial contamination in platelets has been a major concern over the years. In this study, we showed that treatment with 420 nm visible light with various concentrations of riboflavin in platelets reduced E. coli and S. aureus by 0-1.56 and 0.3-2.02 logs (50 mW/cm), 2.24-4.77 and 0.73-3.26 logs (75 mW/cm), and ≥ 5.14 and ≥ 5.27 logs (100 mW/cm). Treatment with high-intensity light (100 mW/cm) and high concentrations of riboflavin (400 µM and 500 µM) effectively reduced both bacteria in platelets by over 4 logs. The study also found a positive correlation between bacterial reduction and light intensity, as well as riboflavin concentration in a dose-dependent manner. These results demonstrate the potential of using riboflavin and visible light to reduce the risk of bacterial contamination in platelets, and support the need for further exploration of pathogen reduction using 420 nm visible light and riboflavin.

Cellular therapy (CT) involving the transplantation of hematopoietic progenitor cells (HPC) is a treatment modality for both benign and malignant disorders. All autologous products require cryopreservation while allogeneic product cryopreservation became more common during the Coronavirus disease 2019 pandemic. Cells are stored in liquid nitrogen (LN) freezers which can malfunction and products may have to be temporarily stored in a mechanical -80 °C freezer if additional LN freezer space is not available. The practice of temporary short-term -80 °C storage is present but there is no study to show that the product is unaffected by the temporary storage at a significantly warmer temperature. In this study, we identified previously collected CT products that were cryopreserved for now-deceased recipients that had remaining cryovials with aliquots of products for quality control purposes. Vials from 20 collections were split into 4 groups of 5 in with one vial placed in temporary storage at -80 °C for 2-5 weeks before returning to LN storage while another vial remained in LN storage for the entire duration of the study. The vials were then simultaneously thawed, processed, and evaluated for total nucleated cell (TNC) and CD34 + cell count and TNC and CD34 + cell viability to determine if there were any differences induced by temporary -80 °C storage. No statistically significant differences were seen after 4 weeks of -80 °C storage; however, after 5 weeks, a statistically significant decrease in TNC viability and viable TNC count, but not CD34 + cell viability and viable CD34 + cell count was observed. These results provide some reassurance to CT processing labs that if there is a failure in their LN storage for cryopreserved products, these products may be safely stored at -80 °C for up to 4 weeks and returned to LN storage without compromising CD34 + cell viability.

Blood transfusion is a cornerstone of modern healthcare, pivotal in saving countless lives annually. However, inadequate knowledge among healthcare providers can lead to serious complications. Despite the availability of assessment tools like the Biomedical Excellence for Safer Transfusion (BEST) test, there is a need for indigenous-validated questionnaires to address knowledge gaps effectively. This study aimed to evaluate bedside transfusion medicine knowledge among clinical residents using a validated questionnaire, focusing on knowledge gaps.

In the realms of extracorporeal photopheresis (ECP), only a few studies have reported the usefulness of circulating microRNAs as predictors of responses. This letter also highlights the putative role of novel organelles termed "migrasomes" in the ECP-triggered immunological responses.