Expired blood transfusion and mortality outcomes in combat trauma patients.

BACKGROUND: Expired blood can be transfused if clinically indicated but outcome data do not exist. We hypothesized that modestly outdated blood can effectively support a hemorrhaging patient until surgical control is achieved. This study assessed whether expired blood was associated with mortality in combat trauma patients. STUDY DESIGN AND METHODS: A retrospective analysis of Armed Services Blood Program and Department of Defense Trauma Registry databases evaluated combat casualty records (2001-2023). The intervention of interest was transfusion of at least one unit of whole blood (WB), red blood cells (RBC), or platelets within one week past expiration. The outcome of interest was mortality at discharge. A control cohort that only received in-date blood was matched to the treatment cohort for logistic regression analysis. RESULTS: One hundred patients received expired RBCs (86), WB (11), and platelets (3). Mortality at discharge was 11.6% for expired RBC recipients and 13.4% for the control cohort (p = .97). After adjustment for injury severity, expired RBCs were not associated with mortality (OR = 0.40 [95% CI, 0.14-1.16]; p = .09). Of 10 patients who received the most expired RBCs by volume or storage duration, two were deceased at discharge. All 14 expired WB and platelet recipients were alive at discharge, but sample sizes were underpowered for regression analysis. DISCUSSION: Transfusion of modestly outdated RBCs was not associated with mortality in combat trauma patients. Expired WB and platelet recipients did well, but sample sizes were too small to draw significant conclusions. Expired blood should be further investigated for possible use in extenuating circumstances.

Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative.

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.

Molecular communication between red blood cells of different phenotypes during blood storage in mice.

BACKGROUND: The cellular and molecular changes during red blood cell (RBC) storage that affect posttransfusion recovery (PTR) remain incompletely understood. We have previously reported that RBCs of different storage biology cross-regulate each other when stored together (co-storage cross-regulation [CSCR]). However, the mechanism of CSCR is unclear. In the current study, we tested the hypothesis that CSCR involves acquisition of molecular signatures associated with PTR. STUDY DESIGN AND METHODS: The whole blood compartment of either B6 or FVB mice was biotinylated in vivo prior to blood collection and storage. Bio-B6 or Bio.FVB were stored with RBCs from B6 mice transgenic for green florescent protein (GFP) (B6.GFP). After storage, avidin-magnetic beads were used to simultaneous purify Bio-RBCs (positive selection) and B6.GFPs (negative selection). Isolated populations were analyzed by transfusion to establish PTR, and subjected to metabolomic and proteomic analysis. RESULTS: B6 RBCs acquired molecular signatures associated with stored FVB RBCs at both the metabolomic and proteomic level including metabolites associated with energy metabolism, oxidative stress regulation, and oxidative damage. Mitochondrial signatures were also acquired by B6 RBCs. Protein signatures acquired by B6 RBCs include proteins associated with vesiculation. CONCLUSION: The data presented herein demonstrate the appearance of multiple molecular changes from poor-storing RBCs in good-storing RBCs during co-storage. Whether this is a result of damage causing intrinsic molecular changes in B6 RBCs or if molecules of FVB RBC origin are transferred to B6 RBCs remains unclear. These studies broaden our mechanistic understanding of RBC storage (in particular) and potentially RBC biology (in general).

Use of half red blood cell units in oncology patients during severe shortages to extend hospital supply.

BACKGROUND: The COVID-19 pandemic exerted an unprecedented impact on the blood supply from 2020 through 2022. As a result, throughout 2021 there were months our hospital had less than one-day supply of type O RBCs. To meet transfusion needs, whole RBC units were split into half units and issued to stable, non-bleeding patients. This single-institution, retrospective study examines time intervals to subsequent transfusion and total numbers of RBC units subsequently transfused after the first half or whole RBC unit. STUDY DESIGN AND METHODS: Patients who were transfused RBC between May 21, 2021 and November 1, 2021 were divided into in- and outpatient groups, then based on whether they received at least 1 half RBC unit or only whole RBC units during the study period. The time interval between this first half unit transfusion, or first whole unit transfusion in those who did not receive half units, and the subsequent RBC transfusion within 90 days was calculated and compared, as well as the total number of RBC units transfused 30 days after the first unit. RESULTS: In general, patients transfused with half units received a subsequent transfusion significantly earlier than those transfused with whole units. Additionally, receiving an index half unit was associated with more RBC transfusions in the following 30 days (p = .001). CONCLUSION: Transfusion of half RBC units during a severe RBC blood shortage can temporarily decrease RBC usage but will result in a shorter interval to the next transfusion and greater total number of RBC units transfused in subsequent days.

In vivo genotoxicity assessment of N-(-9 acridinyl)-b-alanine hydrochloride (S-300) using a validated Pig-a mutagenesis assay.

BACKGROUND: N-(-9 acridinyl)-b-alanine hydrochloride (S-300) is the main byproduct of red blood cell (RBC) amustaline/glutathione(GSH) pathogen reduction, currently undergoing phase III US clinical trials following successful European studies(1-3). Phosphatidylinositol glycan, class A (Pig-a) X-linked gene mutagenesis is a validated mammalian in vivo mutation assay for genotoxicity, assessed as clonal loss of glycosylphosphatidylinositol-linked CD59 cell-surface molecules on reticulocytes (RETs) and RBCs. METHODS: Male Sprague-Dawley rats received continuous infusion of S-300 up to the maximum feasible dose (240 mg/kg/day-limited by solubility and volume) for 28 days. Positive controls received a known mutagen by oral gavage on Days 1-3. Plasma levels of S-300 were assessed by HPLC before, during and after infusion. CD59-negative RBCs and RETs were enumerated in pre-dose and Day 28 samples, using a flow cytometric method. Outcome was evaluated by predetermined criteria using concurrent and historical controls. Toxicity was assessed by laboratory measures and necropsy. RESULTS: S-300 reached maximum, dose-dependent levels (3-15 µmol/L) within 2-8 h that were sustained for 672 h and undetectable 2 h after infusion. Circulating RET levels indicated a lack of hematopoietic toxicity. Necropsy revealed minimal-mild observations related to poor S-300 solubility at high concentrations. Pig-a assessment met the preset acceptability criteria and revealed no increase in mutant RBCs or RETs. CONCLUSIONS: Maximum feasible S-300 exposure of rats by continuous infusion for 28 days was not genotoxic as assessed by an Organization for Economic Cooperation and Development-compliant, mammalian, in vivo Pig-a gene mutation assay that meets the requirements of International Conference on Harmonization (ICH) S2(R1) and FDA guidances on genotoxicity testing.

Preoperative hemoglobin thresholds for increased risk of "medical" complications in fast-track total hip and knee arthroplasty, a secondary analysis of a machine-learning algorithm.

BACKGROUND: There is increasing evidence that gender-specific hemoglobin thresholds may not be ideal in the surgical population. Thus, preoperative anemia defined as a hemoglobin of <13.0 g/dL is a well-established risk factor in elective surgery. However, few studies have investigated the specific influence of preoperative hemoglobin within a machine-learning model using data from an optimized fast-track surgical setup. STUDY DESIGN AND METHODS: A secondary analysis on the specific influence of preoperative hemoglobin level on a machine-learning model developed for identifying patients at increased risk of a length of stay (LOS) of >4 day or readmissions due to medical complications in fast-track total hip and knee arthroplasty within a well-defined fast-track protocol. To evaluate the effect of hemoglobin on the model we calculated SHaply Additive Explanation (SHAP) values for the 3913 patients from our previous test-dataset and stratified by gender and total hip and knee arthroplasty, respectively. RESULTS: The study period ran from January 2017 to August 2017. Median LOS was 1 day and mean preoperative Hb was 15.5 g/dL (SD:1.5), lower in women (14.9 vs. 16.2 g/dL) and with 30.5% of women versus 12.0% of men having a Hb of <13.0 g/dL. There was a steep increase in SHAP value with a preoperative Hb < 14.8 g/dL, and irrespective of gender age and procedure type. DISCUSSION: A machine-learning model found a hemoglobin threshold of <14.8 g/dL for increased risk of impaired recovery, regardless of gender or age, supporting reevaluation of preoperative anemia thresholds in the elective surgical setting.

Iatrogenic blood loss from phlebotomy during adult extracorporeal membrane oxygenation: A retrospective cohort study.

BACKGROUND: Adult extracorporeal membrane oxygenation (ECMO) patients are at high risk for allogeneic blood transfusion. Few studies have characterized iatrogenic blood loss from phlebotomy in adult ECMO patients. We hypothesized that iatrogenic phlebotomy would be a significant source of blood loss during ECMO. METHODS: Adults who had their entire ECMO run at our medical center between 2020 and 2022 were included. Average daily phlebotomy volume and total phlebotomy volume during ECMO were estimated based on the total number of laboratory tests that were processed. In addition, the crude and adjusted association between total phlebotomy volume during ECMO and RBC transfusion during ECMO was evaluated using linear regression and Loess curve analysis. RESULTS: A total of 161 patients who underwent 162 ECMO runs were included. Of the 162 ECMO runs, 88 (54.3%) were veno-arterial and 74 (45.7%) were veno-venous ECMO. Median duration of ECMO was 5 days [25th, 75th percentile = 2, 11]. Median daily phlebotomy volume was 130 mLs [25th, 75th percentile = 94, 170] and median total phlebotomy volume during ECMO was 579 mLs [25th, 75th percentile = 238, 1314]. There was a significant crude and adjusted association between total phlebotomy volume and RBC transfusion during ECMO (beta coefficient = 0.0023 and 0.0024 respectively, both p < .001) based on linear regression analysis. DISCUSSION: Phlebotomy for laboratory testing is a significant source of blood loss during ECMO in adults. Comprehensive patient blood management for adult ECMO patients should include strategies to reduce laboratory testing and/or phlebotomy volume during ECMO.

Radiofrequency identification tracking system (RFID) significantly improves blood bank inventory management and decreases staff work effort.

BACKGROUND: Before implementation of the radio frequency identification (RFID) system, there was a high loss rate of 4.0%-4.3% of red blood cell (RBC) units every year expiring on the shelf in our transfusion service laboratory. We introduced RFID technology to improve inventory management and the burden of work on the staff. The goal of this study was to evaluate the impact of RFID technology on the inventory management of RBC units and the staff workload in a transfusion service laboratory. STUDY DESIGN AND METHODS: Using an RFID system involves encoding RBC units with an RFID tag capturing information such as donor identification number, product code, blood type, expiration date, product volume, and negative antigen(s). Tag information is collected through retrofitted storage shelves linked to the RFID server. The study analyzed RBC usage by unit and by volume (mL) and staff work effort to carry out inventory management tasks before and after the implementation of the RFID system. RESULTS: Implementation of the RFID technology reduced the loss, or discard, of RBC units to less than 1% annually (a statistically significant change, p < .001). The RFID computer dashboard provides a constant visual update of the inventory, allowing technologists to have accurate product counts and reducing their work burden. DISCUSSION: Implementation of RFID technology substantially reduced RBC product loss, improved inventory management, and lessened staff work burden.

Rethinking the transfusion pathway in myelodysplastic syndromes: Study protocol for a novel randomized feasibility n-of-1 trial of weekly-interval red cell transfusion in myelodysplastic syndromes.

BACKGROUND: Anemia in myelodysplastic syndromes (MDS) is associated with poorer health-related quality of life (HRQoL) and physical function, and is frequently treated with transfusions. The current common practice of transfusing multiple red blood cells (RBC) units every 2-4 weeks may result in peaks/troughs in hemoglobin (Hb) level, yet maintaining a stable Hb may better improve HRQoL. We describe a study protocol aiming to investigate the feasibility of weekly low-dose RBC transfusion in MDS patients, including assessing HRQoL and physical function outcomes. STUDY DESIGN AND METHODS: In this n-of-1 pilot study, patients receive two treatment arms, with randomly allocated treatment sequence: arm A (patient's usual transfusion schedule) and arm B (weekly transfusion, individualized per patient). To facilitate timely delivery of weekly transfusion, extended-matched RBCs are provided, with transfusion based upon the previous week's Hb/pre-transfusion testing results to eliminate delays of awaiting contemporaneous cross-matching. Primary outcome is the feasibility of delivering weekly transfusion. Secondary outcomes include HRQoL, functional activity measurements, RBC usage, and alloimmunization rates. A qualitative substudy explores patient and staff experiences. RESULTS: The trial is open in Australia, Netherlands, and UK. The first patient was recruited in 2020. Inter-country differences in providing RBCs are observed, including patient genotyping versus serological phenotyping to select compatible units. DISCUSSION: This pilot trial evaluates a novel personalized transfusion approach of weekly matched RBC transfusion and challenges the dogma of current routine pre-transfusion matching practice. Findings on study feasibility, HRQoL, and physical functional outcomes and the qualitative substudy will inform the design of a larger definitive trial powered for clinical outcomes.

Lack of RBC transfusion independence by Day 30 following allogeneic hematopoietic stem cell transplant strongly predicts inferior survival and high non-relapse mortality in acute myeloid leukemia patients.

BACKGROUND: Studies have suggested that acute myeloid leukemia (AML) patients with incomplete hematologic recovery undergoing allogeneic stem cell transplantation (allo-HSCT) had inferior overall survival (OS). STUDY DESIGN AND METHODS: This single-center, retrospective study of AML patients evaluated the relationship between red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 30 days and long-term outcomes after allo-HSCT through multivariate analyses. RESULTS: A total of 692 AML patients received peripheral blood stem cells (89.2%), marrow (5.6%), or umbilical cord (5.2%) from matched related (37.4%), unrelated (49.1%), or haploidentical (8.2%) donors in 2011-2017. Transfusion requirements during the first 30 days for RBC (89.5% transfused, median 3, range 1-18 units) or PLT (98.2% transfused, median 6, range 1-144 units) were variable. By Day 30, 56.7% (95% confidence interval [CI]: 52.8-60.3%) and 86.1% (95% CI: 83.2-88.5%) had achieved RBC and PLT transfusion independence, respectively. Median follow-up among survivors (n = 307) was 7.1 years (range: 2.7-11.8). Lack of RBC transfusion independence by Day 30 was strongly and independently associated with worse 5-year OS (39.2% vs. 59.6%, adjusted hazard ratio [HR] 1.83, 95% CI: 1.49-2.25), leukemia-free survival (35.8% vs. 55.5%, HR = 1.75, 95% CI: 1.43-2.14), and NRM (29.7% vs. 13.7%, HR = 2.05, 95% CI: 1.45-2.89) (p < .001). There was no difference in relapse rates among patients who achieved or did not achieve RBC (p = .34) or PLT (p = .64) transfusion independence. CONCLUSION: Prolonged RBC dependence predicted worse survival and NRM rates, but not increased relapse. Posttransplant surveillance of such patients should be adjusted with more attention to non-relapse complications.

Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Results of a pilot randomized trial RBC-ENHANCE.

BACKGROUND: The optimal hemoglobin (Hb) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined. STUDY DESIGN AND METHODS: We conducted a pilot randomized multi-center study of two transfusion algorithms (liberal, to maintain Hb 110-120 g/L, transfuse 2 units if Hb < 105 g/L and 1 unit if Hb 105-110 g/L vs. restrictive, 85-105 g/L, transfuse 2 units when Hgb < 85 g/L). Primary objectives were 70% compliance in maintaining the q2 week hemoglobin within the targeted range and the achievement of a 15 g/L difference in pre-transfusion Hb. Secondary outcomes included measures of quality of life (QOL), iron studies and safety. RESULTS: Twenty-eight patients were randomized between February 2015-2020, 13 to the restrictive arm and 15 to the liberal arm in three tertiary care centers. The compliance was 66% and 45% and the mean pre-transfusion Hb thresholds were 86 (standard deviation [SD] 8) and 98 g/L (SD 10) in the restrictive and liberal arms, (mean difference 11.8 g/L, p < .0001), respectively. Patients in the liberal arm experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) more units of blood during the 12-week study. Ferritin increased by 1043 (SD 1516) IU/L and 148 (SD 1319) IU/L in the liberal and restrictive arms, respectively. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important improvements in the liberal arm compared with the restrictive arm for selected symptoms and function domains. CONCLUSION: The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients.

Racial and ethnic differences in transfusion rates in adolescent scoliosis surgery: Preoperative anemia as a mediator of disparity.

BACKGROUND: Pediatric patients from minoritized racial and ethnic groups receive red blood cell (RBC) transfusions more frequently while undergoing major surgical procedures. Our objective was to identify the contribution of preoperative anemia to racial and ethnic differences in RBC transfusion rates in adolescent spine surgery. STUDY DESIGN AND METHODS: This is a multicenter, retrospective cohort study of the National Surgical Quality Improvement Program Pediatric database, 2016 to 2021 for patients in the United States and Canada. RESULTS: Adolescents identifying as non-Hispanic Black, Hispanic, and other race/ethnicity presented with higher rates of preoperative anemia than non-Hispanic White adolescents (16.3%, 10.6%, and 9.9%, vs. 7.8%, respectively; p < .0001) and were transfused at higher rates (14.4%, 11.9%, 16.5%, vs. 10.0%, respectively; p < .0001). Minoritized groups demonstrated higher adjusted odds of RBC transfusion compared with non-Hispanic Whites (non-Hispanic Black: aOR 1.45 95% CI 1.26-1.65, Hispanic: aOR 1.17 95% CI 0.96-1.41, other race/ethnicity: aOR 1.63 95% CI 1.26-2.09). Of the total effect of minoritized race and/or ethnicity on RBC transfusion, 13.9% was attributed to the indirect effect through preoperative anemia. DISCUSSION: In this cohort study, patients from minoritized racial and ethnic groups received RBC transfusions at a higher rate than non-Hispanic White patients, and the difference was partially mediated by preoperative anemia. Future efforts to minimize transfusions and improve health equity should target this modifiable risk factor alongside other sources of disparity and discrimination.

RHD-negative red cells may be avoided for patients with ambiguous serologic typing for the RHD antigen.

BACKGROUND AND OBJECTIVES: Serologic typing with monoclonal anti-D is mandatory for RHD antigen determination before transfusion, but due to aberrant (weak or partial) variants of RHD, results may be ambiguous and molecular RHD-typing is required. Before that, RHD-negative (RHD -) red blood cells concentrates (RBCs) shall be transfused to avoid anti-D formation, which probably leads to wastage of RHD - RBCs. STUDY DESIGN AND METHODS: All patients with ambiguous results in serologic RHD-typing and molecular RHD-typing were assessed retrospectively. The proportions of patients at risk for anti-D formation and the proportion of RHD - RBCs transfused unnecessarily were evaluated for the following transfusion strategies: (1) RHD-positive (RHD + )RBCs for all patients, (2) RHD + RBCs for patients with at least 2+ reaction with anti-D, (3) RHD + RBCs for patients with C and/or E in their RHCE-phenotype, (4) RHD + RBCs for patients with C and/or E and at least 2+ reaction, and (5) RHD - RBCs for all patients. RESULTS: A total of 112 patients were included. Most had weak D type 1-3 and a minority had other, rare RHD variants. The risk of anti-D formation was 4.5%, 2.9%, 1.8%, 1.0%, and 0% for strategies 1-5, respectively. The proportion of RHD - RBCs transfused unnecessarily was 0%, 49.5%, 0.9%, 50.5%, and 95.5%. CONCLUSION: Transfusing patients with a C and/or E in their RHCE-phenotype with RHD + RBCs resulted in a very low risk of immunization while avoiding wastage of RHD - RBCs. Therefore, this strategy should be used for some patients with ambiguous results in serologic RHD-typing and pending results of molecular RHD-typing.

How do we manage hyperhemolysis syndrome.

BACKGROUND: Hyperhemolysis syndrome (HHS) is a catastrophic anemia characterized by destruction of both donor and patient red blood cells (RBC). HHS occurs after transfusion and can cause significant morbidity and mortality. Given the difficulty in diagnosing and managing this process, we provide a detailed overview of our treatment protocol. STUDY DESIGN AND METHODS: Members of the Transfusion Medicine and Hematology faculty at our institution collaborated in an iterative process to produce a consensus approach to patients with HHS. RESULTS: We present diagnostic criteria for HHS: recent transfusion within past 7 days (up to 21 days), rapid hemoglobin decline to below the pretransfusion level (usually hemoglobin drop >25% from pretransfusion), a significant decrease in HbA% (in patients with sickle cell disease or beta thalassemia), low or decreasing reticulocyte count in a patient with worsening anemia, and laboratory evidence of hemolysis. We also describe an in-depth approach to management focusing on optimizing hematopoiesis while dampening the immune response. CONCLUSION: We provide a comprehensive approach to the diagnosis and management of HHS based on contemporary literature and clinical experience designed to optimize outcomes for patients.

Transfusion management and hemoglobin-based oxygen carrier treatment in a patient with anti-Rh17 antibody.

BACKGROUND: A 54-year-old Hispanic OPos female with known history of anti-Rh17 antibodies was diagnosed with Philadelphia-Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Rh17, also known as Hr0, is a high-frequency antigen composed of several epitopes on the RhCE protein. Anti-Rh17 antibodies can be made by individuals with missing or varied C/c, E/e antigens. Anti-Rh17 antibodies are clinically significant given multiple case reports of hemolytic disease of the fetus and newborn (HDFN). Finding compatible units for patients with anti-Rh17 can be particularly difficult given that only 1 in 100,000 people are Rh17 negative. STUDY DESIGN AND METHODS: Search for compatible units was conducted by the American Rare Donor Program (ARDP) with no leads. After chemotherapy induction and despite erythropoiesis stimulating agent administration, the patient's hemoglobin continued to trend down to a nadir of 2.8 g/dL. Here we report transfusion of incompatible pRBC to this patient with critically symptomatic anemia. HBOC-201 (Hemopure) was obtained and administered under an emergency compassionate/expanded access designation from the Food and Drug Administration (FDA) under an emergency Investigational New Drug (IND) application. RESULTS AND DISCUSSION: Overall difficulties in this case included the challenge of finding compatible units, dilemma of transfusing incompatible units in a patient with severe anemia and obtaining alternatives to blood products. This case report demonstrates the successful use of HBOC-21 in treating life-threatening anemia.

Cerebral amyloid angiopathy decades after red blood cell transfusions: a report of two cases from a prospective cohort.

BACKGROUND AND PURPOSE: Patients who underwent red blood cell (RBC) transfusion from donors who later developed multiple spontaneous intracerebral hemorrhages (ICHs) have recently been identified to have increased risk of ICH themselves. This increased risk of ICH was hypothesized to be related to iatrogenic cerebral amyloid angiopathy (iCAA) transmission. Two cases are presented who had RBC transfusion as an infant and presented with CAA at a relatively young age decades later. METHOD: Cases were identified by prospectively asking all patients at our CAA outpatient clinic (November 2023 to January 2024) about a medical history with RBC transfusion or history with a high likelihood for RBC transfusion (e.g., hemolytic disease, trauma with massive hemorrhage). Eligible patients were all diagnosed with CAA, CAA with concomitant hypertensive arteriopathy or iCAA, and without hereditary CAA. RESULTS: Between November 2023 and January 2024, 2/35 (6%, 95% confidence interval 2%-19%) outpatient clinic patients had a history of RBC transfusion and none had a high likelihood medical history. The cases presented at age 47 and 57 and had already developed severe CAA. CONCLUSIONS: Red blood cell transfusion might be a possible mechanism for iCAA; however, further prospective data collection and experimental evidence concerning blood transmission of amyloid-ß are needed.

Red blood cell alloimmunization in myelodysplastic syndromes: Associations with sex, DAT-positivity, and increased transfusion needs.

BACKGROUND: Many patients with myelodysplastic syndromes (MDS) need repeated red blood cell transfusions which entails a risk of immunization and antibody formation. Associations between alloantibodies, autoantibodies and increased transfusion requirements have been reported, but their relationship remains unclear. In this study, we analyzed factors potentially associated with red blood cell alloimmunization, as well as changes in transfusion intensity and post-transfusion hemoglobin increments. METHODS: In a retrospective cohort study, we linked Swedish MDS patients diagnosed between 2003 and 2017 to transfusion and immunohematology data. Potentially associated factors were analyzed using Cox proportional hazards regression. The transfusion rate after detected alloimmunization was analyzed using a fixed effects Poisson regression. Post-transfusion hemoglobin increments before and after alloimmunization were compared using a mixed effects regression. RESULTS: Alloantibodies following MDS diagnosis were detected in 50 out of 429 patients (11.7%). Female sex and a positive direct antiglobulin test (DAT) were independently associated with alloimmunization, with hazard ratios of 2.02 (95% confidence interval [CI] 1.08-3.78) and 9.72 (95% CI, 5.31-17.74), respectively. The transfusion rate following alloimmunization was increased with an incidence rate ratio of 1.33 (95% CI, 0.98-1.80) and the post-transfusion hemoglobin increment after alloimmunization was 1.40 g/L (95% CI, 0.52-2.28) lower per red blood cell unit (p = .002) compared to before alloimmunization, in multivariable analyses. DISCUSSION: Alloimmunization against blood group antigens was associated with sex, DAT-positivity, increased transfusion needs, and lower post-transfusion hemoglobin increments. These findings warrant further investigation to evaluate the clinical significance of up-front typing and prophylactic antigen matching in patients with MDS.

Comparison of three antepartum risk assessment tools to predict significant postpartum hemorrhage in livebirths.

BACKGROUND: To adequately predict significant postpartum hemorrhage (PPH) at hospital admission, we evaluated and compared the accuracy of three risk assessment tools: 1. California Maternal Quality Care Collaborative (CMQCC), 2. American College of Obstetrics and Gynecology Safe Motherhood Initiative (ACOG SMI) and 3. Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN). STUDY DESIGN AND METHODS: This is a retrospective cohort study of people who delivered liveborn infants from January 2018 to June 2021 at our center. Patients with comorbidities necessitating higher hemoglobin values, those who refused blood transfusions, and missing pertinent data were excluded. Significant PPH was defined as a blood transfusion within 48 hours following delivery. Diagnostic statistics were calculated for each tool. RESULTS: Of the 11,679 included pregnancies, 232 (1.9%) people had significant PPH. Amongst those diagnosed as high-risk by the CMQCC tool, 67/1485 (4.5%) had significant PPH; 62/1672 (3.7%) by the ACOG SMI tool, and 85/1864 (4.6%) by the AWHONN tool had significant PPH. All tools have low sensitivity and high negative predictive values. The area under the receiver operating characteristics curve of the three tools is moderately poor (CMQCC: 0.58, ACOG SMI: 0.55, AWHONN:0.61). DISCUSSION: Upon admission to labor and delivery, all three studied tools are poor predictors of significant PPH. The development and validation of better PPH risk stratification tools are required with the inclusion of additional important variables.

Plasma exchange-A useful adjunct therapy to red cell exchange in patients with sickle cell disease and multiorgan dysfunction.

BACKGROUND: Urgent red cell exchange (RBCx) is indicated for many complications of sickle cell disease (SCD), including acute chest syndrome, stroke, and hepatic/splenic sequestration. Many who receive RBCx remain hospitalized and develop further complications, including multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Therapeutic plasma exchange (TPE) has been advocated as an effective treatment of MODS, but its role in SCD compared with RBCx alone is not well studied. METHODS: We identified all ICU encounters from 2013 to 2019 involving RBCx procedures for MODS or SCD crisis that progressed to MODS, a total of 12 encounters. Data regarding hospital length of stay (LOS), survival, number of TPE procedures following RBCx, and procedure characteristics were collected. Surrogate laboratory markers of end-organ damage and disease severity scores were recorded at the time of admission, post-RBCx, post-TPE, and at discharge. RESULTS: Eight encounters involved RBCx followed by TPE (TPE group) while four involved RBCx alone (RBCx group). The TPE group had a higher SOFA score at ICU admission (9.5 vs. 7.0), greater predicted mortality, and a statistical trend toward higher disease severity scores following RBCx relative to the RBCx group (p = 0.10). The TPE group showed a significantly greater decrease in SOFA score between RBCx and discharge (p = 0.04). No significant difference in mortality or hospital LOS was observed between the groups. CONCLUSION: The findings suggest TPE may be considered as an adjunct treatment for patients with acute complications of SCD that progress to MODS, especially in cases where there is no significant improvement following RBCx.

Different-sized extracellular vesicles derived from stored red blood cells package diverse cargoes and cause distinct cellular effects.

BACKGROUND: The formation of extracellular vesicles (EVs) occurs during cold storage of RBCs. Transfusion of EVs may contribute to adverse responses in recipients receiving RBCs. However, EVs are poorly characterized with limited data on whether distinct vesicles are formed, their composition, and potential biological effects. STUDY DESIGN AND METHODS: Stored RBC-derived EVs were purified using protocols that separate larger microvesicle-like EVs (LEVs) from smaller exosome-like vesicles (SEVs). Vesicles were analyzed by electron microscopy, content of hemoglobin, heme, and proteins (by mass spectrometry), and the potential to mediate lipid peroxidation and endothelial cell permeability in vitro. RESULTS: SEVs were characterized by having an electron-dense double membrane whereas LEVs had more uniform electron density across the particles. No differences in hemoglobin nor heme levels per particle were observed, however, due to smaller volumes, SEVs had higher concentrations of oxyHb and heme. Both particles contained antioxidant proteins peroxiredoxin-2 and copper/zinc superoxide dismutase, these were present in higher molecular weight fractions in SEVs suggesting either oxidized proteins are preferentially packaged into smaller vesicles and/or that the environment associated with SEVs is more pro-oxidative. Furthermore, total glutathione (GSH + GSSG) levels were lower in SEVs. Both EVs mediated oxidation of liposomes that were prevented by hemopexin, identifying heme as the pro-oxidant effector. Addition of SEVs, but not LEVs, induced endothelial permeability in a process also prevented by hemopexin. CONCLUSION: These data show that distinct EVs are formed during cold storage of RBCs with smaller particles being more likely to mediate pro-oxidant and inflammatory effects associated with heme.