Organizations in science and medicine must hold each other accountable for discriminatory practices.

Many organizations persist in working with others that engage in known, remediable structural discrimination. We name this practice interorganizational structural discrimination (ISD) and argue it is a pivotal contributor to inequities in science and medicine. We urge organizations to leverage their relationships and demand progress from collaborators.

A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells.

Because apoptosis of infected cells can limit virus production and spread, some viruses have co-opted prosurvival genes from the host. This includes the Epstein-Barr virus (EBV) gene BHRF1, a homolog of human Bcl-2 proteins that block apoptosis and are associated with cancer. Computational design and experimental optimization were used to generate a novel protein called BINDI that binds BHRF1 with picomolar affinity. BINDI recognizes the hydrophobic cleft of BHRF1 in a manner similar to other Bcl-2 protein interactions but makes many additional contacts to achieve exceptional affinity and specificity. BINDI induces apoptosis in EBV-infected cancer lines, and when delivered with an antibody-targeted intracellular delivery carrier, BINDI suppressed tumor growth and extended survival in a xenograft disease model of EBV-positive human lymphoma. High-specificity-designed proteins that selectively kill target cells may provide an advantage over the toxic compounds used in current generation antibody-drug conjugates.

Thrombosis risk with haemoglobin C trait and haemoglobin C disease: A systematic review.

The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild-type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty-two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9-5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9-16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.

Homozygous SPTA1-associated hereditary pyropoikilocytosis presenting as hydrops fetalis.

INTRODUCTION: Hereditary pyropoikilocytosis (HPP) is a heterogeneous inherited disorder of red blood cell (RBC) membrane and cytoskeletal proteins that leads to hemolytic anemia. HPP is characterized by marked poikilocytosis, microspherocytes, RBC fragmentation, and elliptocytes on peripheral blood smear. Mutations in SPTA1 can cause HPP due to a quantitative defect in α-spectrin and can lead to profound fetal anemia and nonimmune hydrops fetalis, which can be managed with intrauterine transfusion. CASE PRESENTATION: We present a case of a 26-year-old G4P2102 woman of Amish-Mennonite ancestry with a pregnancy complicated by fetal homozygosity for an SPTA1 gene variant (SPTA1c.6154delG) as well as severe fetal anemia and hydrops fetalis, which was managed with four intrauterine transfusions between 26 and 30 weeks gestation. Pre-transfusion peripheral smears from fetal blood samples showed RBC morphology consistent with HPP. The neonate had severe hyperbilirubinemia at birth, which has resolved, but remains transfusion-dependent at 6 months of life. DISCUSSION/CONCLUSION: To our knowledge, this is the first report that correlates homozygosity of the SPTA1c.6154delG gene variant with RBC dysmorphology and establishes the diagnosis of HPP.

Gender differences in scholarly productivity of early-career transfusion medicine physicians.

BACKGROUND AND OBJECTIVES: Promotion in academic medicine requires evidence of the creation and dissemination of scholarly output, primarily through peer-reviewed publications. Studies demonstrate that scholarly activity and impact are lower for women physicians than for men physicians, especially during the early stages of their academic careers. This report reviewed physicians' academic productivity after passing their Blood Banking/Transfusion Medicine (BBTM) subspecialty exam to determine if gender discrepancies exist. METHODS: A cross-sectional analysis was designed to determine trends in scholarly activity for women physicians versus men physicians in BBTM. Indexed publications were reviewed using iCite, the National Institutes of Health (NIH) Office of Portfolio Analysis tool, from 1 January 2017 to 1 December 2021, for BBTM examinees who passed the sub-speciality fellowship exam in the years 2016 through 2018. RESULTS: Overall, women physicians had statistically significant fewer total career publications (median 6 vs. 9 cumulative papers, p = 0.03). Women published at a lower rate after passing BBTM boards, which was not statistically significant (0.7 vs. 1.3 publications per year). Other statistically significant findings include fewer early-career BBTM women physicians were first authors compared with men physicians (p = 0.03) and impact as assessed by relative citation ratio was higher for men (p = 0.01). CONCLUSIONS: This study demonstrates that there are gender differences in scholarly productivity and impact on early-career BBTM physicians. Given that this cohort of BBTM physicians are early-career professionals, the significant difference in first authorship publications between women and men physicians is especially concerning. Publication metrics should be followed to ensure equitable research environments for early-career BBTM physicians.

How the United States syphilis epidemic may portend a resurgence of an unusual hematologic condition: The connection between syphilis and paroxysmal cold hemoglobinuria.

The connection between syphilis and paroxysmal cold hemoglobinuria.

New threats from an old foe: Evaluating the risk to the blood supply due to increasing incidence and endemicity of leprosy in the United States.

Leprosy (i.e., Hansen's disease) is a chronic disease secondary to infection with either Mycobacterium leprae or M. lepromatosis. While the incidence of this disease is decreasing across the world, there is mounting evidence that it might be increasing, and becoming endemic, in the United States. Leprosy was once considered a potential threat to the blood supply, and while this threat has not borne out, it is worth revisiting the available data to assess whether it may pose a threat in the future. Herein, we discuss the evidence for and against the potential for transfusion-transmission of leprosy, and highlight future areas of research to further elucidate this possibility.

A multi-institutional survey of apheresis services among institutions in the United States.

INTRODUCTION: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. METHODS: A multi-institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID-19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. RESULTS: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC-A) and red blood cell exchange (RCE). CAR-T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID-19 pandemic, were common and most often addressed using overtime. DISCUSSION: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. CONCLUSION: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers.

Placental Histopathologic Findings in Fetal Hereditary Pyropoikilocytosis after Undergoing Successful Intrauterine Transfusion.

Background: The available literature on intrauterine transfusion focuses largely on its application in fetal alloimmunization rather than hereditary red cell disorders, with limited illustration of its associated histopathologic findings. Case report: We present the histologic findings in a placenta associated with preterm delivery of an infant with autosomal SPTA1 mutation following multiple intrauterine transfusions, including appropriate villous maturation, subchorionic organizing hematomas, hemosiderin-laden macrophages, and dysmorphic fetal erythrocytes within villous capillaries. Conclusion: Intrauterine transfusion is associated with placental histologic findings that reflect procedural changes without significant disruption of placental membranes or villous maturation.

Autoimmune haemolytic anaemia and immune thrombocytopenia following SARS-CoV-2 and non-SARS-CoV-2 vaccination: 32 Years of passive surveillance data.

Autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) are two uncommon haematologic autoimmune conditions that can rarely arise secondary to vaccination. Prior studies using the US Centers for Disease Control's (CDC) Vaccine Adverse Event Reporting System (VAERS) have demonstrated this infrequency, but contemporary data as well as comparison with current information regarding SARS-CoV-2 vaccination has not been assessed. In this study, we reviewed VAERS database reports from 1990 to 2022 to characterize the incidence and clinical and laboratory findings of non-SARS-CoV-2-associated AIHA and ITP and SARS-CoV-2 vaccine-associated AIHA and ITP. We discovered a total of 863 AIHA and ITP reports following vaccination with 15 non-SARS-CoV-2 and four SARS-CoV-2 vaccines submitted to the CDC VAERS database. AIHA and ITP reporting was low for both groups, with a large proportion excluded due to a lack of clinical details. ITP was reported the most frequently in both groups and was significantly more common with measles-mumps-rubella (MMR) vaccination (p < 0.001) in the non-SARS-CoV-2 group. AIHA and ITP cases were higher in the SARS-CoV-2 vaccine group, though ultimately still very infrequent. Autoimmune haematologic disease is vanishingly rare after immunization and rates are lower than in the general population according to passive reporting.

Epidemiological and clinical features, therapeutic strategies and outcomes in patients with hyperhaemolysis: A systematic review.

Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/ß-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.

How do we ensure a safe ABO recheck process?

BACKGROUND: Collecting a patient's blood in a correctly labeled pretransfusion specimen tube is essential for accurate ABO typing and safe transfusion. Noncompliance with specimen collection procedures can lead to wrong blood in tube (WBIT) incidents with potentially fatal consequences. Recent WBIT events inspired the investigation of how various institutions currently reduce the risk of these errors and ensure accurate ABO typing of patient samples. MATERIALS AND METHODS: This article describes the techniques employed at various institutions across the United States to mitigate the risk of misidentified pretransfusion patient specimens. Details and considerations for each of these measures are provided. RESULTS: Several institutions require the order for an ABO confirmation specimen, if indicated, to be generated from the transfusion medicine (TM) laboratory. Others issue a dedicated collection tube that is available exclusively from the TM service. Many institutions employ barcoding for electronic positive patient identification. Some use a combination of these strategies, depending on the locations or service lines from which the specimens are collected. CONCLUSION: The description of various WBIT mitigation strategies will inform TM services on practices that may be effective at their respective institutions. Irrespective of the method(s) utilized, institutions should continue to monitor and mitigate specimen misidentification errors to promote sustained safe transfusion practices.

Analysis of hematologic adverse events reported to a national surveillance system following COVID-19 bivalent booster vaccination.

Hematologic complications, including vaccine-induced immune thrombotic thrombocytopenia (VITT), immune thrombocytopenia (ITP), and autoimmune hemolytic anemia (AIHA), have been associated with the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. However, on August 31, 2022, new formulations of the Pfizer-BioNTech and Moderna vaccines were approved for use without clinical trial testing. Thus, any potential adverse hematologic effects with these new vaccines remain unknown. We queried the US Centers for Disease Control Vaccine Adverse Event Reporting System (VAERS), a national surveillance database, through February 3, 2023, all reported hematologic adverse events that occurred within 42 days of administration of either the Pfizer-BioNTech or Moderna Bivalent COVID-19 Booster vaccine. We included all patient ages and geographic locations and utilized 71 unique VAERS diagnostic codes pertaining to a hematologic condition as defined in the VAERS database. Fifty-five reports of hematologic events were identified (60.0% Pfizer-BioNTech, 27.3% Moderna, 7.3% Pfizer-BioNTech bivalent booster plus influenza, 5.5% Moderna bivalent booster plus influenza). The median age of patients was 66 years, and 90.9% (50/55) of reports involved a description of cytopenias or thrombosis. Notably, 3 potential cases of ITP and 1 case of VITT were identified. In one of the first safety analyses of the new SARS-CoV-2 booster vaccines, we identified few adverse hematologic events (1.05 per 1,000,000 doses), most of which could not be definitively attributed to vaccination. However, three reports of possible ITP and one report of possible VITT highlight the need for continued safety monitoring of these vaccines as their use expands and new formulations are authorized.

Analysis of gender representation on transfusion medicine journal editorial boards: Comparison between 2019 and 2022.

BACKGROUND AND OBJECTIVES: A 2019 study highlighted significant gender inequities among blood banking and transfusion medicine (BBTM) journal editorial boards. We sought to assess if the representation of women has improved in the intervening 3 years. MATERIALS AND METHODS: We analysed the gender composition of nine BBTM journal editorial boards as of 13 September 2022, including the seven journals studied in 2019. We compared this to the proportion of females (term used by authors) on seven BBTM journal editorial boards in 2019 to assess change in the editorial board composition. We also assessed gender composition by editorial position (editor-in-chief [EIC], associate/assistant/titled editors and editorial board members). RESULTS: Nine BBTM journals have a total of 398 editorial positions and comprise significantly more men than women (68.8%, 274/398 vs. 31.2%, 124/398; p < 0.001). Among the seven journals analysed in 2019, the proportion of women on these seven editorial boards has remained unchanged (2019: 30.1%, 81/269 vs. 2022: 31.9%, 103/323; p = 0.66) despite the addition of 54 editorial positions. CONCLUSION: Women remain inequitably represented on journal editorial boards among all journal editorial positions. Although advocacy efforts are increasing, there has been limited improvement in gender equity in 3 years, despite a 20% increase in editorial positions.

United States blood pricing: A cross-sectional analysis of charges and reimbursement at 200 US hospitals.

A violin plot demonstrating listed chargemaster charges for RBC transfusion at 200 hospitals based on hospital ownership. A violin plot shows the volume of the samples at each point by width and lines correspond to the 25th percentile, median, and 75th percentile.

Examining participant representation by sex, race, ethnicity and age in United States blood donation and blood transfusion clinical trials.

Significant inequities based on sex, race, ethnicity, and age exist among participants in clinical trials dedicated to investigating medical disease states. While general demographic data regarding blood donors and blood transfusion recipients have been studied extensively, the demographics of participants involved in blood donation and blood transfusion clinical trials are unknown. We performed a cross-sectional analysis of United States (U.S.) -based interventional blood donation and blood transfusion clinical trials registered with Clinicaltrials.gov to ascertain the composition of participants' sex, race, ethnicity, and age, as well as diagnostic conditions and geographic trial locations.Eligible trials were undertaken between July 2003 and August 2020. Thirty-eight of the one hundred and fifty-two blood donation and blood transfusion clinical trials met inclusion criteria (seven blood donation and thirty-one blood transfusion trials). While the participant dataset from trial reports were incomplete, 100 % of blood donation trials reported sex and age, 71.4 % reported race, and 42.3 % reported ethnicity. 96.8 % of blood transfusion trials reported sex, 51.6 % reported race, 38.7 % reported ethnicity, and 100 % reported age. Among 2720 participants enrolled in the seven blood donation trials, females were underrepresented (28.5 %) compared to U.S. Census data. Conversely, female (50.8 %) and male participants (49.2 %) were equally represented in blood transfusion trials (9255 participants). White participants were overrepresented in blood donation trials (73.4 %), while Hispanic or Latinos were underrepresented in both blood donation (7.7 %) and blood transfusion (8.2 %) trials compared to 2019 U.S.Census data. Only 8.3 % of blood transfusion clinical trials open to adults reported including older adults (i.e., ≥ 65yo). Despite mandatory reporting requirements and an already established framework, researchers frequently failed to report complete demographics of blood donation and blood transfusion clinical trial participants. Furthermore, various demographic groups were underrepresented in blood donation and/or blood transfusion clinical trials, including females, Hispanic or Latino individuals, and older adults. These findings demonstrate the need for implementation of strategies to ensure equitable representation of individuals in blood donation and transfusion clinical trials.

Blood conservation strategies at United States hospitals during the COVID-19 pandemic: Findings from a multi-institutional analysis - International Society of Blood Transfusion survey.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, the transfusion medicine community has experienced unprecedented blood supply shortages since March 2020. As such, numerous changes to everyday practice have occurred with a specific emphasis on blood conservation. We sought to determine the strategies used to mitigate blood shortages and promote blood conservation during the pandemic. METHODS: An anonymous, 37-question survey was developed using Research Electronic Data Capture and distributed via e-mail to transfusion medicine specialists across the US obtained via publicly available databases. RESULTS: Amongst surveyed [41.1% response rate (51/124 institutions)], 98.0% experienced a product shortage, with the greatest number reporting red blood cell (RBC) shortages (92.0%). This led to 35.3% of institutions altering the composition and/or number of blood product suppliers, including a 100% increase in the number of institutions acquiring blood from organizations that connect hospital transfusion services with blood collection centers (e.g., Blood Buy) compared to before March 2020. Prospective triaging of blood products was the most common blood conservation strategy (68.1%), though 35.4% altered their RBC exchange or transfusion program for patients receiving chronic RBC transfusion/exchange. As a result of these changes, 78.6% of institutions reported that these changes resulted in a reduction in blood product usage, and 38.1% reported a decrease in product wastage. CONCLUSIONS: Most hospitals experienced the effects of the supply shortage, and many of them implemented blood conserving measures. Conservation strategies were associated with decreased blood utilization and waste, and future studies could evaluate whether these changes persist.

Liquid biopsies in blood donors: Issues in implementing cell-free DNA cancer screening tests in the blood donor population.

Issues in implementing cell-free DNA cancer screening tests in blood donors.

Blood shortages and changes to massive transfusion protocols: Survey of hospital practices during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has resulted in severe ongoing blood shortages across the US, despite employment of numerous blood-conservation measures. Massive transfusion protocols (MTP) are one resource-intensive practice that utilize significant amounts of blood products. Alterations to the composition of MTP parameters to conserve scarce biologic resources have hitherto not been examined during the pandemic. METHODS: An anonymous 18-question survey was administered to 115 hospitals with valid email contact information. Survey questions addressed whether institutions have altered their MTPs due to the COVID-19 pandemic and blood shortages, and if so, what adjustments they have made. Additional details concerning potential differences in the number and cycles of MTPs and blood product wastage during the COVID-19 pandemic compared to the year prior were assessed. RESULTS: 50 responses were received (43 % response rate). 10 % (5/50) of institutions altered their MTPs utilizing a variety of approaches in attempt to conserve blood during the COVID-19 pandemic. Four additional institutions intend to alter them if it becomes necessary. Following onset of the COVID-19 pandemic, 24 % of institutions (12/50) reported an increase in monthly MTP activations, while 16 % (8/50) reported decreased activations compared to prior to the pandemic. 22 % (11/50) of institutions experienced increased blood wastage, whereas 16 % (8/50) reported decreased waste compared to pre-pandemic. DISCUSSION: The results of this survey highlight a variety of mechanisms by which institutions have attempted to conserve blood via altering MTPs. Whether an institution adjusted their MTP does not correlate with changes in blood product wastage compared to pre-pandemic.

Extracorporeal photopheresis chargemasters show haphazard billing practices.

BACKGROUND: United States healthcare spending continues to outpace other developed nations although efforts are being made to increase cost-transparency. Recent legislation requires hospitals to publish a chargemaster, a list of all billable procedure codes together with prices. Chargemaster prices have been shown to be highly variable, if available, and are not typically paid, but contribute to negotiated rates. Extracorporeal photopheresis (ECP) is performed for a limited number of indications and could serve as a marker of this variability. We investigated the availability of chargemaster documentation for ECP procedures and the variability of pricing as assessed by institutional characteristics. STUDY DESIGN AND METHODS: A list of centers with photopheresis systems was obtained from the device manufacturer and the institutional websites were analyzed for chargemaster list prices. Multivariate linear regressions were performed to compare impact of facility variables on chargemaster pricing. RESULTS: There are 139 locations in the US which are listed as referral centers for ECP; and chargemaster prices were available in 66.2% of these centers. The range was $571.48-183,452.00, maximum price 321 times greater than minimum, and the median price, after outlier exclusion, was $8989.06 (SD = $4361.72). ECP cost did not correlate with hospital size, facility type, ownership, number of hospitals in the referral region, hospital care intensity index, academic status, or region (p ≥ .05). CONCLUSIONS: Chargemaster costs for ECP procedures are highly variable and nonuniform, and the current data available for patients undergoing these specialized apheresis procedures is insufficient to afford patients the ability to compare prices.