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.

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.

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.

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.

Warm autoimmune hemolytic anemia with anti-Jka specificity following babesiosis masquerading as a delayed hemolytic transfusion reaction.

BACKGROUND: Warm autoimmune hemolytic anemia (WAIHA) is characterized by the development of autoantibodies that react with red blood cells (RBCs) optimally at physiologic temperature, classically resulting in a positive direct antiglobulin test (DAT) for IgG and a panreactive eluate. Babesiosis has been described as a potentiator of WAIHA, and all cases have shown classic blood bank findings. Only rare reports have described autoantibodies, both secondary to babesiosis and overall, with specificity for Kidd antigens. METHODS: Antibody detection and identification were performed using IgG-specific column agglutination technology. Jka antigen phenotyping was assessed using monoclonal reagents and genotypic analysis was performed at an immunohematology reference laboratory. DATs were performed via standard tube methods. The elution was performed using the ELUclear glycine acid red cell elution kit. RESULTS: We report a case of WAIHA induced by Babesia microti infection with an autoantibody with Jka specificity, originally believed to be a delayed hemolytic transfusion reaction, given the detection of an RBC antibody in close proximity to numerous RBC transfusions. Determination of autoantibody status with anti-Jka -like reactivity was only confirmed after Kidd antigen genotyping predicted expression of the Jka antigen. DISCUSSION: Healthcare providers should be cognizant of the potential for babesiosis-induced WAIHA, particularly in individuals who continue to hemolyze despite undetectable parasitemia. Furthermore, this case highlights the possibility for warm autoantibodies to demonstrate Kidd antigen specificity. Though Kidd antigen variants are rare, antigen genotyping may be beneficial, particularly in the context of recent RBC transfusions, which typically preclude accurate serological phenotypic assessment.

Survey of blood collection and transfusion practices among institutions in Africa.

INTRODUCTION: Dramatic improvements in blood transfusion have occurred during the last two decades. Transfusion medicine services and practices in Africa remain underexplored. METHODS: A survey of blood bank/transfusion medicine (BBTM) practices, available blood products, blood product source(s), pre-transfusion testing, and blood donor infectious disease testing methodologies across Africa was performed using the American Society for Clinical Pathology (ASCP) listserv. Survey recipients included hospital-based laboratories/blood banks, national transfusion medicine services, and free-standing laboratories (collectively referred to as institutions). RESULTS: Responses from a total of 81 institutions across 22 countries were analyzed. All 81 institutions provide at least one type of blood product-whole blood, red blood cells (RBCs), platelets, plasma, and cryoprecipitate, with whole blood (90.1%, 73 of 81) and RBCs (79.0%, 64 of 81) most common, while cryoprecipitate is least common (12.4%, 10 of 81). Only five countries had a responding institution that provides all types of products. Among institutions that collect blood onsite, the most common sources of blood products are patients' family members (94.1%, 48 of 51) and pre-screened on-demand volunteer donors (82.4%, 42 of 51). The most commonly screened infectious agents are HIV and hepatitis B virus (both 81.5%), while 70.4% (57 of 81) test for hepatitis C virus (HCV) and Treponema pallidum. DISCUSSION: This study highlights significant variability and restrictions in blood product availability, pre-transfusion testing, and blood donor infectious disease testing across Africa. Further studies are needed to ascertain barriers to improving blood donor availability, blood product safety, and infectious disease testing.

Alloimmunization following antigen-negative red blood cell transfusion.

BACKGROUND: Red blood cell (RBC) alloimmunization can occur secondary to transfusion or pregnancy. It is observed most frequently among patients with hemoglobinopathies and myeloid neoplasms. Although previous antigen exposure is generally required for alloimmunization, some alloantibodies may develop naturally without prior exposure. Other alloantibodies may become evanescent, only to reemerge at a detectable titer following a stimulatory event. In a minute fraction of cases, 'non-naturally occurring' alloantibodies may appear without a known antigenic stimulus. METHODS AND MATERIALS: All testing (antibody detection tests and identification, antigen phenotyping, and crossmatching) was performed using the same method and reagents, but occurred at two hospitals within the Yale New Haven Hospital delivery network, and was performed by technologists utilizing different instruments and reagent lots. RESULTS: We present two cases of seemingly de novo alloimmunization (anti-E and anti-K), and one case of re-emergence of a known, previously evanescent alloantibody (anti-K) following transfusion of RBCs that were antigen-negative for the corresponding antibodies. CONCLUSION: While the exact mechanism underlying the development and/or re-emergence of RBC alloantibodies in the absence of antigenic stimulation remains unclear, these cases highlight this unusual phenomenon, underscoring the general immunogenicity, as well as the potential consequences, of RBC transfusion and reiterates the importance of concluding an alloantibody specificity, even in the absence of known transfusion of RBCs with a particular antigen.

Passive transfer of alloantibodies through breast milk as a mediator of hemolytic anemia.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is characterized by destruction of fetal/neonatal red blood cells (RBCs) secondary to maternally derived antibodies, which are typically thought to be passively acquired via placental transfer. Few cases have examined the possibility of HDFN mediated by maternal antibodies passively transferred via breast milk. METHODS: We describe two cases of persistent HDFN in infants potentially mediated by passively acquired antibodies via maternal breast milk. We discuss supporting and refuting evidence that may account for this possibility and describe testing methodology illustrating how maternal alloantibodies can be detected in breast milk. RESULTS: In both cases, anti-D antibodies were detected in maternal breast milk. One patient experienced a significant decrease in anti-D plasma titer from 64 to 4 dilutions following 2 weeks of breastfeeding cessation. The other patient experienced a resolution of anemia without breastfeeding cessation. CONCLUSION: There is a paucity of data regarding the lifespan of passively acquired RBC antibodies in neonatal circulation, with significant variation noted between passively acquired IgG based on studies utilizing intravenous immunoglobulin compared to studies of maternally-acquired antiviral IgG antibodies. While our data do not definitively implicate passive transfer of alloantibodies in breast milk as a mediator of HDFN, they do illustrate the need for further investigation into the mechanisms and kinetics of passively acquired antibodies in neonatal circulation.

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.

A multidisciplinary comparison of transfusion and perioperative support for high-risk cardiac surgery at three large academic centres in North America.

Cardiac surgery is associated with numerous peri- and post-operative haemostatic complications and blood transfusion requirements. Complex procedures such as redo-sternotomy heart transplantation or type A aortic dissection repairs are at high-risk for severe coagulopathy and significant transfusion requirements. However, current practice guidelines do not specifically address high-risk surgeries, resulting in variable practice. To optimise outcomes, a multidisciplinary approach to blood transfusion and haemostasis is critical. How individual institutions construct these multidisciplinary teams, delegate responsibilities, and build procedures may differ depending on the institution and availability of resources. In this article, we compare how the transfusion medicine services support their cardiac surgery and transplant programs at three large medical centres-Vanderbilt University Medical Center (the largest heart transplant centre in the world by volume in 2021), Toronto General Hospital-University Health Network (a quaternary-care centre in Canada's most populous city, performing more >20 heart transplants annually), and Vancouver General Hospital (a quaternary-care centre that performs numerous high-risk cardiac surgeries). This article discusses management from multiple perspectives, including the blood bank and perioperative environments, and highlights how institutions have evolved their programs in accordance with nation-specific policies and provisions.

Botulism mimicking Guillain-Barre syndrome: The question of plasma exchange in an unusual case of acute paralysis.

Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy and the most common cause of acute flaccid paralysis worldwide. GBS classically presents with acute, progressive, ascending weakness, reduced to absent reflexes, and albuminocytological dissociation on cerebrospinal fluid (CSF) analysis. Botulism is a neurotoxin-mediated acute descending flaccid paralysis with cranial nerve palsies and dysautonomia. Botulism in adults is caused by ingestion/inhalation of botulinum toxin or wound infection with Clostridium botulinum. Both GBS and botulism can rapidly precipitate respiratory failure; thus, prompt diagnosis and treatment are crucial to mitigate poor outcomes. Herein, we describe a case of botulism initially diagnosed as GBS given classic laboratory features, and describe the importance of careful consideration of the most appropriate therapeutic modalities in cases of acute flaccid paralysis, particularly regarding empiric administration of botulinum antitoxin and use of intravenous immune globulin in lieu of plasma exchange for potential GBS to prevent removal of antitoxin.

Immunity in the balance: Fatal disseminated adenovirus infection in a patient undergoing plasma exchange and immunosuppressive chemotherapy for anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease (formerly known as Goodpasture's syndrome) is a rare autoinflammatory condition that affects the renal and/or pulmonary capillaries. The standard therapeutic regimen for anti-GBM disease involves therapeutic plasma exchange (TPE), cyclophosphamide, and corticosteroids to rapidly remove and inhibit autoantibody production and reduce organ inflammation. Herein we report an 82-year-old female who developed anti-GBM disease but expired despite therapy, secondary to multi-organ failure in the setting of disseminated adenovirus disease. We discuss the utility and potential adverse effect of daily TPE for a protracted course (ie, 10-14 days), the recommended TPE intensity in the 2023 American Society for Apheresis guidelines, updated from every-other-day TPE in the 2019 guidelines, despite no new data. We also highlight the potential for unusual infections to occur in these patients due to the profound immunosuppression, and discuss the importance of balancing immunosuppression to treat the disease with close surveillance of any potential opportunistic infections.

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.