Objective:Platelet transfusion thresholds for very low birth weight (VLBW, <1500g) infants vary widely, and the role of bleeding on platelet transfusion thresholds is unknown. Study Design:This observational birth cohort study of VLBW infants born in 7 hospitals across the US examined pre-transfusion platelet counts in infants with and without bleeding who received at least 1 platelet transfusion in the first 3 weeks of life using mixed effect linear regression models. Results:Of the 210 transfused infants, most (76%) had bleeding; intraventricular hemorrhage (IVH) was the most common (61%) bleeding type. Pre-transfusion platelet counts were not different among infants with or without bleeding diagnoses (56.3 vs 58.5×103/μL, respectively; P=0.7). However, infants with severe IVH had higher platelet counts (68.9×103/μL) compared to the entire cohort (53.5×103/μL, P=0.01). Conclusion:Infants with or without bleeding diagnoses had similar pre-transfusion platelet counts; infants with severe IVH had higher pre-transfusion platelet counts.

Many poly(amine-co-ester) (PACE) nanoparticles, drug delivery vehicles for nucleic acid and small molecule cargoes, accumulate in the liver and spleen following intravenous administration, limiting delivery to nonhepatosplenic tissues. Red blood cell (RBC) hitchhiking, a strategy in which nanoparticles are nonspecifically adsorbed to RBCs prior to administration, has been used to modulate nanoparticle biodistribution, enabling enrichment in organs immediately downstream from the site of vascular infusion. We find that scarcely investigated cellular determinants-namely, storage duration, membrane stiffness, and membrane-bound sialic acid quantity-substantially affect PACE nanoparticle adsorption efficiency. Following development of an optimized adsorption protocol, RBC hitchhiking was shown to enhance PACE nanoparticle cargo delivery to pulmonary tissue while also increasing exposure to other assayed organs. These findings inform future RBC hitchhiking study design, implicate cellular variables as potential obstacles or boons to clinical translation, and demonstrate the delivery of nucleic acids using this strategy with the PACE nanoparticle platform.

BACKGROUND:Prior studies have evaluated transfusion recipient variables impacting red blood cell (RBC) alloimmunization, but few focused on potentially modifiable blood donor or blood component variables. STUDY DESIGN AND METHODS:Data from the Recipient Epidemiology and Donor Evaluation Study (REDS)-III, which links donor, component, and patient data in an integrated database, were accessed. For any given RBC unit with sufficient blood donor and component data, we determined if the transfusion recipient experienced a new RBC alloimmunization event ("case") within 16 weeks of the transfusion or not ("control"). Recipient diagnoses were included in the case-control matching algorithm. RESULTS:A total of 2676 cases were matched with 10,160 controls. In a multivariate conditional logistic regression analysis, recipients who received an RBC unit from donors with a different ABO group had a higher risk of alloimmunization (OR 1.60, 95% CI: 1.35-1.89, p < .001). Likewise, recipients who received RBCs from older donors had a higher risk of RBC alloimmunization (OR 1.01 per year of age, 95% CI: 1.00-1.01, p < .001). Irradiated RBCs were associated with a decreased risk of RBC alloimmunization in transfusion recipients (OR 0.52, 95% CI: 0.46-0.59, p < .001), though a sub-analysis of RBCs transfused to people with sickle cell disease showed no such association (p = .75). Recipients who received RBCs stored for a longer duration also had a lower risk (OR 0.99 per day of storage, 95% CI: 0.99-0.99, p < .001) of alloimmunization. DISCUSSION:This case-control study identified donor and component variables associated with recipient RBC alloantibody formation. Future mechanistic studies exploring these associations are warranted.

OBJECTIVE:To evaluate if hematologic thresholds for red blood cell (RBC) and platelet transfusions changed over time following publication of new evidence from randomized trials in a multicenter cohort of extremely low birth weight (ELBW) infants. STUDY DESIGN:We analyzed data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-IV-Pediatrics study from April 2019 through December 2023. We compared pretransfusion hemoglobin and platelet counts closest to each transfusion within 24 hours by year using linear mixed models and used model interaction terms to determine if trends over time differed by postnatal weeks. RESULTS:We evaluated 981 ELBW infants. For trends in RBC transfusion thresholds, 785 infants (80%) received 5182 RBC transfusions, of which 4835 (93%) had a pretransfusion hemoglobin value. Pretransfusion hemoglobin declined over time (P < .0001), with trends differing by postnatal week (interaction P = .005). The greatest year-over-year decline in pretransfusion hemoglobin was in the third postnatal week or later. For platelet transfusions, 221 infants (23%) received 934 platelet transfusions, of which 900 (96%) had a corresponding pretransfusion platelet count. There was no change in pretransfusion platelet count over time (P = .24). These trends did not differ by postnatal week (interaction P = .14), although pretransfusion platelet counts were lower after the first postnatal week (P < .001). CONCLUSIONS:In this cohort of US centers, we observed declines in pretransfusion hemoglobin but not pretransfusion platelet counts from 2019 to 2023. These findings suggest evidence from recent RBC and platelet transfusion threshold trials may have been differentially translated into clinical practice for ELBW infants.

In 2014, the Organ Procurement and Transplant Network (OPTN) permitted the allocation of A2 and A2B kidneys to group B candidates with low anti-A titers to increase access. To determine recipient eligibility, the OPTN requires anti-A titers with transplant centers determining eligibility titer cutoff. Historically, blood banks have performed antibody titers using AHG (AHG titers). However, titers for these types of transplants are routinely performed with Dithiothreitol (DTT)- treated serum (DTT titers). DTT disrupts IgM’s disulfide bonds; as such, reactivity is attributed solely to IgG. It was this method that was described in seminal literature of A2/A2B to B transplants. Consequently, the transplant program requested DTT titers to evaluate out-of-group eligibility; thus, the aim herein is to describe our experience transitioning from AHG titers in tube to DTT titers in tube. Validation was performed using serum from twenty group B transplant candidates. For AHG titers, plasma and A1 red cells were incubated for 60 minutes at 37 °C followed by AHG after washing. For DTT titers plasma was treated with 0.01 M DTT followed by a 10-minute, room temperature incubation with A1 red cells. Titers were completed using serial titration up to a 1:32 dilution. Titers <8 were considered eligible for an A2 transplant. We then compared our results to a comparator lab, which ran the samples using our protocol. DTT titers were also performed at dilution 1:8, with a titer < 8 indicating eligibility for an out-of-group transplant. Overall, the tube DDT titers resulted in lower titers compared to tube AHG titers (18/20; 90%). Interestingly, of the 10 samples that were ineligible by AHG, 5 became eligible by DTT. The correlation of tube DTT titers performed in our laboratory and the comparator laboratory was high (90%), and those that differed did not impact the eligibility status. The correlation between running a full serial tube titration and a single titration performed at the 1:8 cut-off dilution also had a high correlation of 95%. In summary, tube DTT results were expectedly lower than AHG tube titers, which could lead to increased eligibility and access to transplant for group B transplant candidates. The study with the comparator lab demonstrated high correlation, helping to validate the DTT titer method. Additionally, DTT results performed at one dilution (1:8) appeared equivalent to serial titration to determine eligibility. Performing titers at a single dilution would help with workflow, given the time it takes for manual tube titrations. Moving forward, we plan to evaluate this procedure for group O transplant candidates.

Transfusion-induced anti-red blood cell (RBC) alloantibodies pose a significant risk to patients who require chronic transfusions. Anti-RBC alloantibodies can be remarkably short-lived (i.e. evanescent), leading to clinically relevant alloantibodies that are not detected in later pre-transfusion antibody screens. Subsequent transfusion of alloantigen-positive RBCs stimulates a rapid memory antibody response that may induce a delayed hemolytic transfusion reaction (DHTR), causing morbidity and occasional mortality in chronically transfused patients. It is unclear why transfusions favor evanescent antibody responses over long-lived antibodies typically observed upon infections and vaccinations. We therefore turned to the HOD mouse model of RBC alloimmunization to elucidate regulators of antibody persistence in response to allogenic transfusions. By following antibody responses over time in transfused mice, we found that HOD-specific alloantibodies rapidly decay within three months while vaccination-induced antibodies remain constant. Thus, the HOD model recapitulates RBC antibody evanescence. The rapid antibody evanescence suggests that transfusion is a poor inducer of germinal centers (GCs), specialized immunological structures where B cells differentiate into germinal center B (GC B) cells and undergo iterative rounds of affinity maturation, ultimately differentiating into long-lived plasma cells that can produce antibodies for decades. Consistent with this hypothesis, we failed to observe an increase in GC B cell formation in response to transfusion, and the majority of anti-RBC alloantibodies were low affinity when compared to vaccination. To formally test the functional requirement for GCs in anti-RBC alloantibody production, we employed two orthogonal approaches to disrupt GC formation: i) day 4 CD40L blockade and ii) genetic disruption of the GC-transcription factor BCL6 selectively in B cells. Both approaches fully blocked GC formation, yet anti-RBC alloantibody production was unchanged. Collectively, our data demonstrate that anti-HOD RBC alloantibodies are GC-independent, low affinity and short-lived. The GC-independence of HOD RBC IgG responses has important implications for understanding the cellular and molecular pathways that regulate the humoral immune response to transfused RBCs, potentially explaining anti-RBC alloantibody evanescence patterns in patients. ### Competing Interest Statement The authors have declared no competing interest.

Achieving an adequate dose of genetically modified hematopoietic stem cells (HSCs) for gene therapy in patients with sickle cell disease (SCD) remains a challenge due to limitations related to stem cell mobilization using plerixafor alone, reduced apheresis collection efficiency, and losses during ex vivo cell manipulation. To date, 39 SCD patients were enrolled in NHLBI-funded Phase I (NCT03282656; PMC7962145) and NHLBI/CIRM-funded multi-site Phase II (NCT05353647) gene therapy trials to receive autologous CD34+ HSCs transduced with a lentiviral vector encoding a short hairpin RNA embedded in a microRNA (shmiR) targeting BCL11A. To collect HSCs as the starting material for drug product manufacture (minimum 4×10⁶ cells/kg), apheresis (minimum 4 blood volumes or up to 8 hours) was performed within 3 hours of daily plerixafor for 2 consecutive days. A third day of collection was used to generate a back-up product as needed. Mean mobilized, pre-apheresis peripheral blood (PB) CD34+ count was 40 cells/μL (range 7–126). Among 35 evaluable patients (4 excluded: 1 pending release, 3 withdrew), 74% (26/35) reached target CD34+ collection in a single mobilization cycle (mean 2.6 procedures, range 2–6). Manufacturing was achieved with a mean of 11.92×10⁶ CD34+ cells/kg collected resulting in a drug product of 7.04×10⁶ CD34+ cells/kg and a net cell recovery from apheresis to drug product of 62% (range 38–91%). Drug products were successfully generated for all patients with a mean product vector copy number of 4.04 copies/cell (range 1-7). The time interval from first collection cycle to completion of product testing was a median of 39 days (mean 56) for all patients, and a median of 37 days (mean 38) for those collected in 1 cycle. Preparative transfusions were given before collections to bridge patients after stopping hydroxyurea or to mitigate stress erythropoiesis. We examined the impact of preparative transfusion on mobilization and apheresis efficiency in 16 evaluable patients at a single site. All underwent ≥ 3 months of preparative transfusion with a HbS target of ≤30% before mobilization using simple transfusion or automated red cell exchange. The mean HbS% at mobilization was 10.8% (range 2.9–21.5%). Overall, the preparative transfusion regimen reduced PB reticulocyte percentage by 50% to a mean of 7.2% (range 3.7–12.3), indicating decreased stress erythropoiesis. Resting PB CD34+ counts before and after 3-months of transfusion were 10.8 cells/μL (range 2–21) and 6.2 cells/μL (range 1–13), respectively. A total of 39 mobilization/collection procedures were performed in 16 patients with a mean post-plerixafor CD34+ count of 43 cells/μL (range 13–85) with collections performed between the two darkest color preferences of the manufacturer. Cell collection preference was monitored using real-time intraprocedural CD34+ cell sampling. A mean of 4.3 total blood volumes was processed (range 2.5–6.4), with mean collection efficiency (CE) (CD34+ cells collected ÷ [pre-apheresis CD34+ count × total blood processed]) of 48% (range 8.2–107.1). The mean reticulocyte percent in patients with CE <30% (11.4%, range 2.5 –18.9) was significantly higher than in those with CE >30% (6.2%, range 1.8–11.9, p=0.0026). Two patients had a history of delayed hemolytic transfusion reactions and/or multiple RBC alloantibodies before study entry that limited preparative transfusions to reach a HbS of 30% for 3 months. They were successfully collected, and products were generated after simple transfusions with a single limited-volume red cell exchange immediately prior to collection. The success of this study was driven by optimizing apheresis strategies, including suppression of stress erythropoiesis through transfusion, real-time instrument adjustments, and efficient manufacturing that allowed a collection target of nearly half the CD34+ cells recommended in the FDA-approved gene product. Strikingly, the highly efficient ex vivo manipulation platform described here enables successful mobilization and manufacturing of gene therapy products for SCD in several months, easing the path to autologous gene therapy for SCD.

Focal segmental glomerulosclerosis (FSGS) is one of the causes of end-stage kidney disease. The etiology is not fully understood, and standardized treatments are not established. We created a registry on apheresis for post-transplant FSGS through the Renal Subcommittee in the Research Committee in the American Society for Apheresis (ASFA), and here is our first report. Members of the renal subcommittee from seven centers in the United States contributed data collection on demographic, clinical course, and overall outcomes of patients with post-transplant recurrence of FSGS treated with therapeutic plasma exchange (TPE) between 2015 and 2020. The TPE data, including frequency and replacement fluid for TPE, are also investigated. The median age at diagnosis of FSGS and first transplantation among 26 patients was 12.7 and 21 years, respectively. The FSGS recurred at a median of 1 day after transplantation, and TPE was performed daily or every other day in the first month and continued at some frequency beyond a year in some cases. Most procedures used albumin as a replacement fluid and citrate anticoagulation, with 1-1.5 plasma volumes exchange. Twelve patients had complete/partial remission by 6 months. The median urine protein/creatinine ratio improved from 4.47 to 1.4 mg/mg within 3 months, and eGFR improved from 26 to 78 mL/min/1.73 m2 in a year after TPE started. The study revealed some uniformity in the prescription of TPE, primarily using albumin as replacement fluid and performing 1-1.5 plasma volume exchanges. Observed complication rates were minimal. TPE can be one of the treatments to consider in this condition.

BACKGROUND: Alloimmunization to transfused red blood cells (RBCs) remains a significant clinical problem. However, the cells that initiate immune responses to transfused RBCs remain incompletely characterized. Recently published work has identified splenic marginal zone B (MZB) cells as being critically required for the production of anti-RBC alloantibodies in response to RBCs. In infectious models, MZB cell activation has been shown to depend on a unique population of marginal zone macrophages (MZMs). We hypothesized that MZMs would capture stored RBCs and present them to MZBs, and ultimately MZMs would be required for generation of anti-RBC alloantibodies in response to stored RBC transfusion. STUDY DESIGN AND METHODS: Stored GFP+ murine RBCs were utilized to determine the splenic localization and erythrophagocytosis by splenic macrophage populations. To determine the functional impact of MZMs, we compared LXRα-KO mice, which have been reported to lack MZMs, with wild type mice. Both innate and adaptive immune responses to stored HOD allogenic RBC transfusion were measured in LXRα-KO and wild type mice. RESULTS: RBC storage leads to a significant increase in the phagocytosis of transfused RBCs by splenic MZMs. LXRα-KO mice demonstrated a lack of MZMs and had significantly decreased rapid phase production of cytokines MCP-1 and KC, but similar levels of IL-6. Surprisingly, anti-RBC alloantibody levels were unaffected by the absence of splenic MZMs. CONCLUSIONS: Splenic MZMs are involved in the innate response to transfused stored HOD RBCs, contributing to both MCP-1 and KC cytokine production. However, MZMs are dispensable for anti-RBC alloantibody production. ### Competing Interest Statement The authors have declared no competing interest.

Red blood cell (RBC) alloimmunization to non-ABO antigens is a major clinical complication for chronically transfused patients. When exposed to transfused RBCs carrying foreign antigens, some patients generate IgG antibodies that target these antigens, creating potential barriers to future transfusions. Interestingly, other patients produce only IgM antibodies against the same non-ABO antigens, which generally have fewer clinical consequences. Despite the stark differences in their impact, the factors regulating IgM versus IgG production in response to transfused RBCs remain poorly understood. This study explores the balance between IgM and IgG production following transfusion, comparing it to the well-characterized antibody response induced by vaccination in mouse models. By directly assessing antibody levels following RBC transfusion versus Alum-adjuvanted vaccination, we demonstrate that transfusion of RBCs expressing a model antigen is a relatively weak inducer of IgG class switching. Additionally, loss-of-function experiments using CD40L blockade and CD4 depletion confirmed that T cell help is essential for class switching after transfusion but has no effect on IgM production. Most notably, providing supra-physiological levels of T cell help enhanced class switching in a dose-dependent manner after transfusion, whereas vaccination-induced class switching remained unaffected. These findings support a model in which the limited IgG class switching following transfusion stems from suboptimal T cell help compared to vaccination. Furthermore, they suggest that transfusion activates T cells through a non-canonical pathway, distinct from the mechanisms driving immune responses to standard Alum vaccination. ### Competing Interest Statement The authors have declared no competing interest.

Hyperviscosity syndrome (HVS) is defined as the symptomatic presentation of increased blood thickness due to various clinical conditions such as hypergammaglobulinemia. HVS secondary to immunoglobulin (Ig)A multiple myeloma has been infrequently reported. Although the efficiency of IgM or IgG removal by therapeutic plasma exchange (TPE) is well described, the efficiency of IgA removal by TPE is not as well known. Here, we describe a case of HVS due to IgA myeloma in a patient who received 2 TPE treatments, with subsequent symptomatic improvement as well as decrease in IgA and viscosity levels.

Transfusion of red blood cells (RBCs) can be lifesaving for individuals living with sickle cell disease (SCD). However, alloimmunization following transfusion is more common with SCD than other patient populations, resulting in morbidity and mortality. Management of complications related to RBC alloantibodies, including delayed hemolytic transfusion reactions (DHTRs) and identifying compatible RBCs for future transfusions, remains a challenge for hematologists and transfusion medicine providers. Although transfusion guidelines from organizations including the American Society for Hematology provide general recommendations, individual cases remain challenging. Antibody evanescence and the lack of widespread RBC alloantibody data sharing across hospitals pose unique challenges, as do RH variants in both transfusion recipients and blood donors. Further, as potentially curative therapies require RBC transfusions to lower the hemoglobin S prior to cellular therapy collections and infusions, highly alloimmunized patients may be deemed ineligible. The cases described are representative of clinical dilemmas the authors have encountered and the approaches are as evidence-based as the literature and the authors' experiences allow. A future desired state is one in which RBC alloantibody data are efficiently shared across institutions, Rh alloimmunization can be mitigated, better treatments exist for DHTRs, and a label of "difficult to transfuse" does not prevent desired therapies.

Red blood cell alloimmunization and consequent delayed hemolytic transfusion reaction (DHTR) incidence and mortality in patients with sickle cell disease (SCD) are high. A shared transfusion resource has decreased both in other countries, while in the United States cost concerns persist. We conducted a Markov cohort simulation of a birth cohort of alloimmunized patients with SCD to estimate lifetime DHTR incidence, DHTR-specific mortality, quality-adjusted life expectancy (QALE), and costs with the implementation of a shared transfusion resource to identify antibody history versus without (i.e., status quo). We conducted our analysis using a lifetime analytic time horizon and from a United States health system perspective. Implementation of shared transfusion resource projects to decrease cumulative DHTR-specific mortality by 26% for alloimmunized patients with SCD in the United States, relative to the status quo. For an average patient population of 32 000, this intervention would generate a discounted increment of 4000 QALYs at an incremental discounted cost of $0.3 billion, resulting in an incremental cost-effectiveness ratio of $75 600/QALY [95% credible interval $70 200-81 400/QALY]. The results are most sensitive to the baseline lifetime medical expenditure of patients with SCD. Alloantibody data exchange is cost-effective in 100% of 10 000 Monte Carlo simulations. The resource would theoretically need a minimum patient population of 1819 patients or cost no more than $5.29 million annually to be cost-effective. By reducing DHTR-specific mortality, a shared transfusion resource in the United States projects to be a life-saving and cost-effective intervention for patients with SCD in the United States.

Data from hemovigilance systems and studies suggest that a disproportionate number of transfused children experience transfusion reactions compared with adults (Vossoughi et al., 2018; Oakley et al., 2015; Lavoie, 2011; Gauvin et al., 2006). This chapter will focus primarily on acute transfusion reactions in children, including recognition and management in the pediatric surgical setting.

Background- Pediatric Patient Blood Management (PBM) programs require continuous surveillance of errors and near misses. However, most PBM programs rely on passive surveillance methods. Our objective was to develop and evaluate a set of automated trigger tools for active surveillance of pediatric PBM errors. Materials and methods- We used the Rand-UCLA method with an expert panel of pediatric transfusion medicine specialists to identify and prioritize candidate trigger tools for all transfused blood products. We then iteratively developed automated queries of electronic health record (EHR) data for the highest priority triggers. Two physicians manually reviewed a subset of cases meeting trigger tool criteria and estimated each trigger tool's positive predictive value (PPV). We then estimated the rate of PBM errors, whether they reached the patient, and adverse events for each trigger tool across four years in a single pediatric health system. Results- We identified 28 potential triggers for pediatric PBM errors and developed 5 automated trigger tools ( positive patient identification, missing irradiation, unwashed products despite prior anaphylaxis, transfusion lasting >4 hours, over-transfusion by volume). The PPV for ordering errors ranged from 38-100%. The most frequently detected near miss event reaching patients was first transfusions without positive patient identification (estimate 303, 95% CI: 288-318 per year). The only adverse events detected were from over transfusions by volume, including 4 adverse events detected on manual review that had not been reported in passive surveillance systems. Discussion- It is feasible to automatically detect pediatric PBM errors using existing data captured in the EHR that enable active surveillance systems. Over-transfusions may be one of the most frequent causes of harm in the pediatric environment.

TransfusionVolume 64, Issue 4 p. 761-762 LETTERS TO THE EDITOR Red blood cell alloimmunization in patients on extracorporeal membrane oxygenation Ayda Javanbakht, Ayda Javanbakht orcid.org/0009-0003-7353-3633 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USASearch for more papers by this authorThomas M. Schneider, Thomas M. Schneider orcid.org/0000-0002-8160-4775 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USASearch for more papers by this authorJeanne E. Hendrickson, Corresponding Author Jeanne E. Hendrickson [email protected] orcid.org/0000-0002-7928-3132 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA Correspondence Jeanne E. Hendrickson, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA. Email: [email protected]Search for more papers by this author Ayda Javanbakht, Ayda Javanbakht orcid.org/0009-0003-7353-3633 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USASearch for more papers by this authorThomas M. Schneider, Thomas M. Schneider orcid.org/0000-0002-8160-4775 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USASearch for more papers by this authorJeanne E. Hendrickson, Corresponding Author Jeanne E. Hendrickson [email protected] orcid.org/0000-0002-7928-3132 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA Correspondence Jeanne E. Hendrickson, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA. Email: [email protected]Search for more papers by this author First published: 09 April 2024 https://doi.org/10.1111/trf.17761Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Raasveld SJ, Karami M, Schenk J, Dos Reis MD, Mandigers L, Dauwe DF, et al. Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: a multicenter retrospective observational cohort study. Transfusion. 2023; 63: 1809–1820. 10.1111/trf.17505 CASPubMedWeb of Science®Google Scholar 2Urban M, Gazdic T, Slimackova E, Pirk J, Szarszoi O, Maly J, et al. Alloimmunosensitization in left ventricular assist device recipients and impact on posttransplantation outcome. ASAIO J. 2012; 58: 554–561. 10.1097/MAT.0b013e31826d6070 CASPubMedWeb of Science®Google Scholar 3Arachchillage DRJ, Owen S, Anievas M, Gaspar M, Laffan M. Red cell alloimmunisation in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO). Intensive Care Med. 2020; 46: 1932–1933. 10.1007/s00134-020-06051-0 PubMedWeb of Science®Google Scholar 4Zheng Y, Pollak J, Henderson K, Hendrickson JE, Tormey CA. A novel association between high red blood cell alloimmunization rates and hereditary hemorrhagic telangiectasia. Transfusion. 2018; 58: 775–780. 10.1111/trf.14451 CASPubMedWeb of Science®Google Scholar Volume64, Issue4April 2024Pages 761-762 ReferencesRelatedInformation

BACKGROUND:Increasing indications for cellular therapy collections have stressed our healthcare system, with autologous collections having a longer than desired wait time until apheresis collection. This quality improvement initiative was undertaken to accommodate more patients within existing resources.STUDY DESIGN AND METHODS:Patients with multiple myeloma who underwent autologous peripheral blood stem cell collection from October 2022 to April 2023 were included. Demographic, mobilization, laboratory, and apheresis data were retrospectively collected from the medical record.RESULTS:This cohort included 120 patients (49.2% male), with a median age of 60 years. All received G-CSF and 95% received pre-emptive Plerixafor approximately 18 hours pre-collection. Most (79%) had collection goals of at least 8 × 106/kg CD34 cells, with 63% over 70 years old having this high collection goal (despite 20 years of institutional data showing <1% over 70 years old have a second transplant). With collection efficiencies of 55.9%, 44% of patients achieved their collection goal in a single day apheresis collection. A platelet count <150 × 103/μL on the day of collection was a predictor for poor mobilization; among 27 patients with a low baseline platelet count, 17 did not achieve the collection goal and 2 failed to collect a transplantable dose.CONCLUSIONS:With minor collection goal adjustments, 15% of all collection appointments could have been avoided over this 6-month period. Other strategies to accommodate more patients include mobilization modifications (Plerixafor timing or substituting a longer acting drug), utilizing platelet counts to predict mobilization, and modifying apheresis collection volumes or schedule templates.

Background:Studies of human patients have shown that most anti-RBC alloantibodies are IgG1 or IgG3 subclasses, though it is unclear why transfused RBCs preferentially drive these subclasses over others. Though mouse models allow for the mechanistic exploration of class-switching, previous studies of RBC alloimmunization in mice have focused more on the total IgG response than the relative distribution, abundance, or mechanism of IgG subclass generation. Given this major gap, we compared the IgG subclass distribution generated in response to transfused RBCs relative to protein in alum vaccination, and determined the role of STAT6 in their generation.Study Design and Methods:WT mice were either immunized with Alum/HEL-OVA or transfused with HOD RBCs and levels of anti-HEL IgG subtypes were measured using end-point dilution ELISAs. To study the role of STAT6 in IgG class-switching, we first generated and validated novel STAT6 KO mice using CRISPR/cas9 gene editing. STAT6 KO mice were then transfused with HOD RBCs or immunized with Alum/HEL-OVA, and IgG subclasses were quantified by ELISA.Results:When compared to antibody responses to Alum/HEL-OVA, transfusion of HOD RBCs induced lower levels of IgG1, IgG2b and IgG2c but similar levels of IgG3. Class switching to most IgG subtypes remained largely unaffected in STAT6 deficient mice in response to HOD RBC transfusion, with the one exception being IgG2b. In contrast, STAT6 deficient mice showed altered levels of all IgG subtypes following Alum vaccination.Discussion:Our results show that anti-RBC class-switching occurs via alternate mechanisms when compared to the well-studied immunogen alum vaccination.

BACKGROUND:Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy.STUDY DESIGN AND METHODS:The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions. Outcomes included mortality, sepsis, and subsequent platelet transfusion requirements.RESULTS:Following adjustment for possible confounding factors, no statistically significant association between ABO non-identical platelet transfusion and increased risk of mortality was observed in the overall cohort of 21,176 recipients. However, when analyzed by diagnostic category and recipient ABO group, associations with increased mortality for major mismatched transfusions were noted in two of eight subpopulations. Hematology/Oncology blood group A and B recipients (but not group O) showed a Hazard Ratio (HR) of 1.29 (95%CI: 1.03-1.62) and intracerebral hemorrhage group O recipients (but not groups A and B) showed a HR of 1.75 (95%CI: 1.10-2.80). Major mismatched transfusions were associated with increased odds of receiving additional platelet transfusion each post-transfusion day (through day 5) regardless of the recipient blood group.DISCUSSION:We suggest that prospective studies are needed to determine if specific patient populations would benefit from receiving ABO identical platelet units. Our findings indicate that ABO-identical platelet products minimize patient exposure to additional platelet doses.