Search

SummaryDifferential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between these two disease states, with increased heterogeneity and multi-organ involvement in MIS-C encompassing diverse cell types such as endothelial and neuronal Schwann cells. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory signaling pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level, multi-analyte view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers.

Context.— Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. Objective.— To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. Design.— We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. Results.— Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. Conclusions.— For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype–guided management of Rh immune globulin therapy and RBC transfusions.

Delayed transfusions may result in patient morbidity and mortality, but no standards for timely transfusion have been developed. Information technology tools could be implemented to identify gaps in provision of blood and to recognize areas of improvement. Herein, we propose that the time to initiate a blood transfusion after an informative laboratory test could feasibly be used by the transfusion medicine service as a metric to monitor for transfusion delays. Trends and outlier events could be further investigated and used to make decisions and implement protocols to improve patient care.

To present consensus statements and supporting literature for plasma and platelet product variables and related laboratory testing for transfusions in general critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children.Not applicable.Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions.None.A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for laboratory testing and blood product attributes for platelet and plasma transfusions. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed five expert consensus statements and two recommendations in answer to two questions: what laboratory tests and physiologic triggers should guide the decision to administer a platelet or plasma transfusion in critically ill children; and what product attributes are optimal to guide specific product selection?The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding program provides some guidance and expert consensus for the laboratory and blood product attributes used for decision-making for plasma and platelet transfusions in critically ill pediatric patients.

BACKGROUND As evidence demonstrating the importance of early transfusions in trauma resuscitation accumulates, when RhD-negative products might not be available, it is important to understand the nature of the RhD-type of products provided to bleeding pediatric patients of potentially unknown RhD-type. METHODS A survey link was electronically sent to the transfusion service medical director and/or laboratory manager at American pediatric Level I and Level II hospitals inquiring about their practices for selecting RhD-type of uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) for boys and girls. RESULTS There were 55/117 (47.0%) analyzable responses; 43/55 (78.2%) from Level I and 12/55 (21.8%) from Level II hospitals. For in hospital transfusions, 51/55 (92.7%) of centers use only RhD-negative blood products to resuscitate girls ≤18 years old while 30/55 (54.5%) of centers do the same for boys ≤18 years old. Most centers 41/55(74.5%) store RBCs and/or LTOWB in in-hospital remote refrigerators; 27 store only RhD-negative RBCs and 2 store only RhD-negative LTOWB units in these refrigerators. A total of 24/55 (43.6%) centers have RBCs and/or LTOWB available on road ambulances or helicopters for prehospital transfusion; 12 transport only RhD-negative RBCs and two transport only RhD-negative LTOWB. Most centers, 35/55 (63.6%), address the prophylaxis of an RhD-negative female recipient of RhD-positive transfusion on a case-by-case basis. CONCLUSION While there is some variability, most of the responding pediatric trauma centers routinely utilized RhD-negative RBCs for emergency transfusion for patients ≤18 years old of unknown RhD-type.

Background It is unclear whether placental changes in ZIKV infection influence short- and long-term child outcomes. The objective of this study is to determine if placental histopathology findings in ZIKV correlate with offspring outcomes at birth and age 4-5 years for children with in utero ZIKV exposure without congenital Zika syndrome. Methods 24 placentas collected from pregnant women with symptomatic ZIKV infection enrolled in a prospective ZIKV study in Colombia were formalin fixed and reviewed by a placental pathologist, blinded to child outcome. Children had neuroimaging as newborns and were longitudinally evaluated to age 4-5 years with the Bracken School Readiness Assessment (BSRA) and Pediatric Evaluation of Disability Inventory (PEDI-CAT). Scores were compared by presence of placental findings of perivillous fibrin deposition, calcifications, and increased syncytial knotting. T-test, fisher exact, and one way ANOVA were used for analysis; significance, p< .05. Results All 24 placentas had at least one abnormal pathological finding (Table 1). 14 (58%) placentas had extensive ( >30% coverage) and 7 (29%) had mild-moderate perivillous fibrin deposition (Fig. 1a). Placental calcifications were many ( >10) in 10 (42%) cases, and mild in 7 (29%) cases (Fig. 1b). 14 (58%) placentas had increased syncytial knotting. Placentas stained positive with CD163 for Hofbauer macrophages (Fig. 1c). All infants were born at term with normal birth weight, height, and head circumference, and 22 had a normal ponderal index. There was no difference in measurements based on each placental finding. There was no relationship between placental findings and non-specific neuroimaging. 20 (83%) children with placentas were evaluated at age 4-5. Children without placental calcifications scored higher on BSRA than children with mild/severe calcifications (p = .031). Children with increased syncytial knotting had lower scores on PEDI-CAT social/cognitive ability (p = .024). Conclusion Placentas from ZIKV-infected pregnancies have pathological findings that indicate risk of impaired fetal perfusion, but these were not associated with preterm birth or growth. There may be associations between placental findings and long-term neurodevelopment in ZIKV-exposed children requiring additional studies. Disclosures All Authors: No reported disclosures.

MIS-C is a severe hyperinflammatory condition with involvement of multiple organs that occurs in children who had COVID-19 infection. Accurate diagnostic tests are needed to guide management and appropriate treatment and to inform clinical trials of experimental drugs and vaccines, yet the diagnosis of MIS-C is highly challenging due to overlapping clinical features with other acute syndromes in hospitalized patients. Here we developed a gene expression-based classifier for MIS-C by RNA-Seq transcriptome profiling and machine learning based analyses of 195 whole blood RNA and 76 plasma cell-free RNA samples from 191 subjects, including 95 MIS-C patients, 66 COVID-19 infected patients with moderately severe to severe disease, and 30 uninfected controls. We divided the group into a training set (70%) and test set (30%). After selection of the top 300 differentially expressed genes in the training set, we simultaneously trained 13 classification models to distinguish patients with MIS-C and COVID-19 from controls using five-fold cross-validation and grid search hyperparameter tuning. The final optimal classifier models had 100% diagnostic accuracy for MIS-C (versus non-MIS-C) and 85% accuracy for severe COVID-19 (versus mild/asymptomatic COVID-19). Orthogonal validation of a random subset of 11 genes from the final models using quantitative RT-PCR confirmed the differential expression and ability to discriminate MIS-C and COVID-19 from controls. These results underscore the utility of a gene expression classifier for diagnosis of MIS-C and severe COVID-19 as specific and objective biomarkers for these conditions.

Background In the setting of suspected septic transfusion reactions, bacterial culture of both the transfused patient and the residual blood component is recommended. Primary bacterial contamination can occur at the time of component collection. Clinically insignificant "secondary contamination" can occur during post-transfusion component discard, retrieval for culture, or manipulation of the bag at the time of culture sampling. Study design and methods This retrospective, multi-center study analyzes positive residual component culture results and companion patient blood cultures from 15 hospitals, 1 blood center, and all cultured transfusion reactions within the province of Quebec, Canada, over a 5-year period. Imputability was assigned as "definite" (concordant growth), "possible" (discordant growth or lack of growth in patient culture), or "unable to assess" (patient not cultured). Results There were 373 positive component cultures from 360 unique transfusion reactions, with 276 (76.7%) companion patient blood cultures performed, of which 10 (2.8%) yielded the pathogen detected in the positive component. Of these 10 definite pathogens, 7 (2 Staphylococcus aureus, 3 other staphylococci, and 1 Streptococcus pyogenes and 1 Bacillus sp.) were associated with platelet and 3 (Aeromonas veronii, Staphylococcus epidermidis, and Enterococcus faecalis) with RBC transfusions. RBC and plasma components comprised 70% of positive component cultures. Discussion The process of performing residual component culture is vulnerable to secondary contamination. The significance of microorganisms recovered from component culture cannot be interpreted in isolation. In the context of low prevalence of primary contamination of blood components, the positive predictive value of a positive component culture result is very low.

BACKGROUND There are limited standards guiding the selection and processing of blood components specific for neonatal and pediatric transfusions. Therefore, blood banks (BBs) and transfusion services must create their own policies and procedures. STUDY DESIGN AND METHODS The American Association of Blood Banks (AABB) Pediatric Transfusion Medicine Subsection Committee developed a 74-question survey to capture neonatal and pediatric BB practices in the United States. RESULTS Thirty-five centers completed the survey: a response rate 15.8%. Responses indicated that most carry a mixed inventory of red blood cells (RBCs); 94.2% allow more than one type of RBC product for small-volume (SV) and large-volume (LV) transfusions to neonatal and pediatric patients. Many had storage age thresholds for RBCs transfused to neonates (SV = 60%, LV = 67.7%) but not older pediatric patients. The use of Group O for nonurgent RBC transfusion in neonates was common (74.2%). Responses related to special processing of RBCs and platelets indicated that 100% RBC and platelets are leukocyte-reduced (LR) for neonates and 97% for non-neonates. Irradiation of RBCs and platelets was commonly performed for neonatal transfusion (88.6%). Providing cytomegalovirus (CMV) seronegative products, volume reduction, and washing were variable. All centers transfused single-donor apheresis platelets; 20% allowed pathogen reduction (PR). The majority of centers have strategies limiting the amount of incompatible plasma transfused; however, few titrate ABO isoagglutinins in plasma-containing products (20% for platelets and 9.1% for plasma). CONCLUSIONS Variability exists in BB practice for neonatal and pediatric transfusion. Future studies are needed to understand and define best BB practices in these patient populations.

Background Patients with sickle cell disease (SCD) are frequent recipients of red blood cell (RBC) transfusions and are at risk for RBC alloimmunization. RBC alloimmunization is diagnosed by identifying RBC alloantibodies as part of pre-transfusion testing, but this testing fails to detect alloantibodies that have evanesced. It may be beneficial to screen for new RBC alloantibody development after transfusion before possible antibody evanescence. Study design and methods Our institution started a new initiative for episodically transfused patients with SCD to obtain at least one antibody screen 2-6 months after transfusion as part of their clinical care. A database was created to prospectively track all transfused patients for 1 year and their post-transfusion antibody screen results. Patients received prophylactically CEK-matched RBC units. Results During the study year, 138 patients with SCD received a total of 242 RBC transfusions. Patients with a history of an RBC alloantibody (n = 13, 9.4%) had previously received more RBC units than non alloimmunized patients (median 11 vs. 2 RBC units, p = .0002). A total of 337 post-transfusion antibody screens were obtained in 127 patients (92.0%) with 110 patients (79.7%) having at least one antibody screen 2-6 months post-transfusion. With this prospective testing, two new RBC alloantibodies (anti-C and -M) were identified in two patients. Conclusion It is feasible to test for new RBC alloantibody development in most episodically transfused patients with SCD as part of their routine care. The yield of this screening appears low with CEK matching, but it could still provide important information for individual patients.

Background Transfusions are a common intervention within pediatrics and require unique considerations to optimize patient care. Poor knowledge of evidence-based transfusion practice can lead to misuse of transfusion therapy and harm. While there have been assessments of transfusion medicine knowledge of physicians caring for adult patients, there is little data regarding pediatricians. Study design and methods Using a published transfusion medicine knowledge exam for internal medicine physicians as a backbone, pediatric transfusion medicine experts, using an iterative process, developed a pediatric-specific examination. Pilot testing and Rasch analysis, a method used in high-stakes testing, was used to validate the exam. The exam and a previously validated survey on transfusion medicine training, attitudes, and perceived ability were administered to pediatric residents. Analysis consisted of descriptive statistics as well as comparisons of exam scores based on survey responses. Results 330 pediatric residents from 19 sites in 6 countries participated in the study. The vast majority (91%) of residents had obtained blood product consent. The mean exam score was 37.1% (range 9.5%-71.4%) with no statistical differences based on amount or perceived quality of transfusion medicine education or perceived ability. Discussion A rigorously validated exam has now been developed that can be used to assess pediatric transfusion medicine knowledge. A large international group of pediatric residents performed poorly on the exam demonstrating a pressing need for improved transfusion medicine education to ensure safe and appropriate administration of blood components to infants and children.

BackgroundChildren are an important population to test for COVID-19 infection, particularly because they may shed the virus without displaying symptoms. Testing children for COVID-19 via sensitive molecular methods is important, although collecting nasopharyngeal (NP) specimens can be challenging. A less invasive mode of specimen collection that yields test results comparable to those from NP specimens would be beneficial to simplify sample collection.MethodsTo demonstrate that saliva is a suitable specimen for collection from children, the clinical usability/acceptability and the analytic performance of saliva were compared to NP specimens suspended in viral transport medium. Four different FDA EUA-approved real-time RT-PCR assays and one EUA approved saliva collection device were investigated.ResultsThe study population included 526 patients between the ages of 3 and 61 years, 461 (88%) were ConclusionsOf the four FDA EUA-approved SARS-CoV-2 PCR assays studied, we found the AllPlex assay to be best suited for testing saliva specimens collected from children 5 years of age or older. The sensitivity of viral detection was equivalent to NP specimens when saliva specimens were mixed with the saliva stabilizer.

Children require transfusion of blood components for a vast array of medical conditions, including acute hemorrhage, hematologic and nonhematologic malignancies, hemoglobinopathy, and allogeneic and autologous stem cell transplant. Evidence-based literature on pediatric transfusion practices is limited, particularly for non-red blood cell products, and many recommendations are extrapolated from studies in adult populations. Recognition of these knowledge gaps has led to increasing numbers of clinical trials focusing on children and establishment of pediatric transfusion working groups in recent years. This article reviews existing literature on pediatric transfusion therapy within the larger context of analogous data in adult populations.

BACKGROUND Hyperkalemia is a rare life-threatening complication of red blood cell (RBC) transfusion. Stored RBCs leak intracellular potassium (K+) into the supernatant; irradiation potentiates the K+ leak. As the characteristics of patients and implicated RBCs have not been studied systematically, a multicenter study of transfusion-associated hyperkalemia (TAH) in the pediatric population was conducted through the AABB Pediatric Transfusion Medicine Subsection. STUDY DESIGN The medical records of patients

Background: The WHO recommends that pre-transfusion testing should include ABO/RhD grouping followed by screen- ing for red blood cell (RBC) alloantibodies using the indirect antiglobulin test (IAT). However, in Uganda, current practice does not include RBC alloantibody screening. Objective: To assess the utility of ‘home-made’ reagent RBCs in alloantibody screening. Materials and methods: In a laboratory-based study, group O RhD positive volunteer donors were recruited and their extended phenotype performed for C, c, E, e, K, Fya, Fyb Jkb, S and s antigens. These ‘home-made’ reagent RBCs were preserved using Alsever’s solution and alloantibody detection tests performed. For quality assurance, repeat alloantibody screening of patients’ samples was done at Bloodworks Northwest Laboratory in Seattle, United States. Results: A total of 36 group O RhD positive individuals were recruited as reagent RBC donors (median age, 25 years; range, 21 – 58 years; male-to-female ratio, 1.6:1). Out of the 311 IATs performed, 32 (10.3%) were positive. Confirmatory IAT testing in the United States was in agreement with the findings in Uganda. Conclusion: Use of ‘home-made’ reagent RBCs during pre-transfusion testing in Uganda is feasible. We recommend the introduction of pre-transfusion IAT alloantibody screening in Uganda using ‘home-made’ reagent RBCs to improve trans- fusion safety. Keywords: Blood transfusion; ‘Home-made’ reagent RBCs; Pre-transfusion testing; RBC alloantibody screening; Uganda.

The supply of blood in many low- and middle-income nations in Sub-Saharan Africa (SSA) does not meet the patient care needs. Lack and delay of blood transfusion cause harm to patients and slow the rate of progress in other parts of the health system. Recognizing the power of implementation science, the BLOODSAFE Program was initiated which supports three SSA research study teams and one data coordinating center (DCC) with the goal to improve access to safe blood transfusion in SSA.The study team in Ghana is focusing on studying and decreasing iron deficiency in blood donors and evaluating social engagement of blood donors through different approaches. The study team in Kenya is building a "vein to vein" workflow model to elucidate and devise strategies to overcome barriers to blood donation and improve infrastructural components of blood product production and use. The Malawi team is studying the infectious disease ramifications of blood donation as well as blood donor retention strategies aimed at blood donors who commence their donation career in secondary schools.Together the project teams and the DCC work as a consortium to support each other through a shared study protocol that will study donor motivations, outcomes, and adverse events across all three countries. The BLOODSAFE Program has the potential to lead to generalizable improvement approaches for increasing access to safe blood in SSA as well as mentoring and building the research capacity and careers of many investigators.

Background Transfusion medicine is the only section of the clinical laboratory that performs diagnostic testing and dispenses a drug (blood) on the basis of those results. However, not all of the testing that informs the clinical decision to prescribe a blood transfusion is performed in the blood bank. To form a holistic assessment of blood bank responsiveness to clinical needs, it is important to be able to merge blood bank data with datapoints from the hematology laboratory and the electronic medical record. Methods We built an interactive visualization of the time from hemoglobin result availability to initiation of red blood cell (RBC) transfusion and monitored the result over a 2-year period that coincided with several severe blood shortages. The visualization runs entirely on free software and was designed to be feasibly deployed on a variety of hospital information technology platforms without the need for significant data science expertise. Results Patient factors, such as hemoglobin concentration, blood type, and presence of minor blood group antibodies influenced the time to initiation of transfusion. Time to transfusion initiation did not appear to be significantly affected by periods of blood shortage. Conclusion Overall, we demonstrate a proof of concept that complex, but clinically important, blood bank quality metrics can be generated with the support of a free, user-friendly system that aggregates data from multiple sources.

Background Anti-red blood cell (RBC) alloantibodies consisting of only the immunoglobulin G (IgG) 4 subtype are typically considered clinically insignificant. A US Food and Drug Administration-approved monoclonal anti-human globulin (16H8) is nonreactive with IgG4, which has been considered a benefit to avoid testing interference from IgG4. However, 16H8 also does not recognize two natural IgG3 variants (IgG3-03 and IgG3-13). Thus, 16H8 may miss clinically significant alloantibodies in some settings. Study design and methods Novel mouse anti-human IgG hybridomas were generated and screened for reactivity with 32 human variants of anti-KEL1 across different IgG subtypes, as well as mutants to allow epitope mapping. Anti-IgG reactivity was determined using KEL1+ RBCs bound by each IgG variant as targets. Binding of anti-IgG was determined by flow cytometry. Results 16H8 recognized an epitope involving amino acid 419, which is glutamate in IgG4, IgG3-03, and IgG3-13, explaining the lack of 16H8 reactivity with these subtypes/isoallotypes. A new monoclonal antibody (PUMA8) was isolated that, like 16H8, was nonreactive with IgG4 but without blind spots for known variants of IgG1, IgG2, or IgG3. PUMA8 recognized an epitope containing arginine at position 355, which is glutamine in IgG4. However, a recently described new IgG4 variant with an arginine at position 355 results in PUMA8 reactivity. Conclusion PUMA8 represents an alternative to 16H8 that avoids IgG4 but without blind spots for IgG3 variants. However, PUMA8 reacts with one recently described IgG4 variant. In addition to relevance to immunohematology, these studies highlight the importance of patient variation with regards to assay performance in an era of personalized medicine.

The United States Food and Drug Administration Final Guidance for Industry titled, "Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion" provides nine strategies for platelet bacterial risk mitigation. Even if it is assumed all strategies are comparable in terms of safety and efficacy, the decision of which to implement remains challenging. Some additional factors that warrant evaluation before selecting a strategy include the financial impact, process for implementation, logistics upon implementation, institutional acceptance by blood bank staff, administration and clinicians, and effect on platelet availability. To assist with this difficult choice, a panel of transfusion service physicians who have expertise on the topic and have already selected strategies for their transfusion services were recruited to provide varied perspectives. In addition, the use of a decision-making tool that objectively evaluates defined criteria for assessment of the nine strategies is described.

ObjectivesBlood transfusion is life-saving for patients experiencing acute blood loss and severe anaemia. In low-income and middle-income countries (LMICs), low blood donation rates and unavailability of whole blood and blood components (blood products) impairs timely blood transfusion. To fulfil patient-specific blood orders, a hospital blood transfusion service (HBTS) receives orders from a prescriber for blood transfusion, tests and prepares blood products for the patient. This study sought to describe the current state of LMIC HBTS.DesignA cross-sectional survey explored LMIC HBTS access to blood products, testing methods, policies and structure. Surveys were administered in English, Spanish, French and Russian, followed by a mixed-methods analysis.SettingHBTS within LMICs.ParticipantsFrom among 124 public and private facilities invited to participate, we received 71 (57%) responses. Of these responses, 50 HBTS from 27 LMICs performed on-site blood transfusions.ResultsMost LMIC HBTS perform blood collection to generate blood products for their patients (36/47, 77%); few relied exclusively on an external supply of blood products (11/47, 23%). The primary reason for blood transfusion was adult anaemia for non-malignant conditions (17/112, 15%). Testing methods varied by gross national income per capita. Blood transfusion delays to patients were common (17/30, 57%) attributed to inadequate blood inventories (13/29, 45%). Other barriers included lack of regular clinician education about transfusion (8/29, 28%) and sustainable financial models for the HBTS (4/29, 14%).ConclusionThis survey describes the status of HBTS in diverse LMICs, illustrating that the availability of blood products remains a principal problem, requiring HBTS to generate its own facility’s blood supply. Currently, blood shortages are not reported as a patient-specific adverse event making systematic tracking of delays in transfusion difficult. These findings highlight areas for further exploration related to the lack of available blood inventories for transfusions at HBTS in LMICs.

BACKGROUND: The COVID-19 pandemic has brought tremendous challenges to the United States blood supply. Decreased collections have caused blood product shortages. The number of hospital-based donor centers (HBDCs) has decreased in the past decades, but they provide important support to their hospital systems. MATERIALS/METHODS: We identified 79 active HBDCs through an information request to the FDA. These centers were invited to participate in a survey about their activities, blood product collections, and perceived value. RESULTS: Thirty-six centers responded (46% response rate). The centers represented a wide range of states and geographic settings. Whole blood collection was most common, but some respondents also prepared specialized products such as COVID-19 convalescent plasma and pathogen-reduced platelets. Positive impacts of HBDCs included inventory availability, cost-effectiveness/savings, community outreach, supporting special patient populations, and collecting specialty products. All respondents anticipate at least stable operations, if not growth, in the future. CONCLUSION: HBDCs continue to be valuable assets in addressing emerging patient transfusion needs. Their unique offerings are tailored to the populations their hospitals support, and demonstrate the value in having the collection infrastructure in place to rapidly respond to critical shortages. This survey provides benchmark data about a broad group of HBDCs including products prepared, inventory self-sufficiency levels, and reasons for positive impact.

Objectives:To describe the incidence of seasonal respiratory viral infections (s-RVIs) before and during the coronavirus disease 2019 (COVID-19) pandemic and to compare virus-specific patient outcomes in pediatric patients.Design:A retrospective cross-sectional study including patient admissions to the Children’s National Hospital between October 1, 2015, and December 31, 2020.Results:Among 12,451 patient admissions between March 15 and December 31, 2020 (cohort 1), 8,162 (66%) were tested for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and 249 (2.0%) were positive. Among 10,986 patient admissions between April 1 and December 31, 2020 (cohort 2), 844 (8%) were tested for s-RV upon admission and 160 were positive. Thus, 1.5% of patient admissions were associated with laboratory-confirmed s-RVIs. Among the 49,901 patient admissions during a viral season between October 1, 2015, and March 31, 2020 (cohort 3), 7,539 (15%) were tested for s-RV upon admission and 4,531 were positive; thus, 9.0% of patient admissions were associated with laboratory-confirmed s-RVIs. hHRV/rENT was the most detected virus, but the detection rate decreased substantially (31% vs 18%; P < .001) during the COVID-19 pandemic. No patients had RSV, influenza, hMPV, hPIV, or hCoV detected upon admission after April 21, 2020. The 3 patient cohorts had no statistically significant difference in the percentage of ICU admissions (10.8% vs 15.0% vs 14.2%; P > .05) or death at discharge (0.8% vs 0.6% vs 0.5%; P > .05).Conclusions:Compared to COVID-19, s-RVI cases were associated with a higher proportion of inpatient admissions but were similar in ICU admission and death rates in hospitalized pediatric patients. Public health interventions for preventing COVID-19 were highly effective in preventing pediatrics s-RVIs.

Background Culturing residual blood components after suspected septic transfusion reactions guides management of patients and cocomponents. Current practice, accuracy of provider vital sign assessment, and performance of the AABB culture criteria are unknown. A multicenter international study was undertaken to investigate these issues and develop improved culture criteria. Study design and methods Retrospective data for all transfusion reactions resulting in residual blood component culture in 2016 were collected from participating hospitals. The performance of the AABB culture criteria were assessed for detection of positive culture results. Modifications to the AABB criteria including 1) recommending culturing in the setting of isolated high fevers, 2) defining hypotension and tachycardia using objective parameters, and 3) incorporating antipyretic use were tested to determine if modifications improved performance. Modifications associated with improvement were incorporate into the BEST criteria. The AABB and the BEST criteria were then tested against a data set enriched for positive culture results to determine which criteria were superior. Results Data were collected from 20 centers encompassing 779,143 transfusions, 3,187 reported transfusion reactions, and 1,104 cultured components. There was marked variation in reaction reporting and culturing rates (0.0%-100.0%). Of 35 total positive component cultures, only one of 35 (2.9%) had concordant patient cultures; 12 of 34 (35.3%) did not have patient cultures performed. The BEST criteria had better sensitivity for detection of a positive culture result compared to the AABB criteria (74% vs. 41%), although specificity decreased (45% vs. 65%). Conclusion Compared to the AABB criteria, the BEST criteria have improved sensitivity for positive culture detection.

Purpose Rh antigens can provoke severe alloimmune reactions, particularly in high-risk transfusion contexts such as, sickle cell disease. Rh antigens are encoded by the paralogs, RHD and RHCE, located in one of the most complex genetic loci. Our goal was to characterize RH genetic variation in multi-ethnic cohorts, with the focus on detecting RH structural variation (SV). Methods We customized analytical methods to estimate paralog-specific copy number from next generation sequencing (NGS) data. We applied these methods to clinically-characterized samples, including four WHO genotyping references and 1135 Asian and Native American blood donors. Subsequently, we surveyed 1715 African American samples from the Jackson Heart Study. Results Most samples in each dataset exhibited SV. SV detection enabled prediction of the immunogenic RhD and RhC antigens in concordance (>99%) with serological phenotyping. RhC antigen expression was associated with exon 2 hybrid alleles (RHCE*CE-D(2)-CE). Clinically-relevant exon 4-7 hybrid alleles (RHD*D-CE(4-7)-D) and exon 9 hybrid alleles (RHCE*CE-D(9)-CE) were prevalent in African Americans. Conclusions This study shows custom NGS methods can accurately detect RH SV, and that SV is important to inform prediction of relevant RH alleles. Additionally, this study provides the first large NGS survey of RH alleles in African Americans.

BACKGROUND Wrong blood in tube (WBIT) errors can lead to ABO mistransfusions. It is unknown if WBIT errors are more likely in specific healthcare locations or if specific collection practices influence the commission of WBIT errors. STUDY DESIGN AND METHODS Data on pretransfusion samples from calendar year 2019 were collected retrospectively by 39 transfusion services in nine countries. We compared the proportion of WBIT errors made in emergency departments (EDs), inpatient wards, and outpatient clinics. RESULTS In total, 143 WBIT errors were detected among 1,394,862 samples for an unadjusted aggregate WBIT proportion of 1.03/10,000 samples. Using a pooled random effects model, the WBIT proportion was estimated to be significantly higher in EDs (1.23/10,000 samples, 95% CI 0.62-2.43) than inpatient wards (0.71/10,000, 95% CI 0.44-1.14; p

The estimated severe acute respiratory syndrome coronavirus 2 seroprevalence in children was found to be 9.46% for the Washington Metropolitan area. Hispanic/Latinx individuals were found to have higher odds of seropositivity. While chronic medical conditions were not associated with having antibodies, previous fever and body aches were predictive symptoms.

The evolution of SARS-CoV2 virus has led to the emergence of variants of concern (VOC). Children, particularly

Background T-antigen activation usually occurs upon red blood cell (RBC) membrane cryptantigen exposure due to bacterial enzymes. Although uncommon, the condition is probably underrecognized. There is concern about hemolysis after plasma and plasma-containing platelet transfusions due to naturally occurring anti-T antibody in healthy blood donors. However, experts have debated the extent and severity of clinical hemolysis due to anti-T. Procedure We retrospectively identified patients who tested positive for polyagglutination with Arachis hypogea and Glycine max lectins from 2008 to 2019. The records of the patients were reviewed to determine clinical symptoms, laboratory evidence of hemolysis, need for transfusion, and clinical outcomes. Results Ten patients were identified. At diagnosis, all were anemic and four had thrombocytopenia. Severe Streptococcus pneumoniae infection affected seven patients; one died. Seven of 10 patients (70%) had laboratory evidence of hemolysis. Peripheral blood smear findings in six patients included RBC agglutination and changes suggesting hemolysis (spherocytes and schistocytes), but three had unremarkable RBC morphology. Four patients required plasma or platelet transfusions; all survived to discharge. Conclusions T-antigen activation is a rare entity. Most patients diagnosed at our hospital had hemolytic anemia and severe pneumococcal infection. Hemoglobin decreased after plasma and platelet transfusions in all patients assessed, but these transfusions were necessary to support treatment. RBCs were given to maintain appropriate hemoglobin levels.

The SARS-CoV-2 virus has emerged as a global pandemic, severely impacting everyday life. Significant resources have been dedicated towards profiling the viral genome in the adult population. We present an analysis of viral genomes acquired from pediatric patients presenting to Children’s National Hospital in Washington D.C, including 24 with primary SARS CoV2 infection and 3 with Multisystem Inflammatory Syndrome in Children (MIS-C) undergoing treatment at our facility. Viral genome analysis using next generation sequencing indicated that approximately 81% of the analyzed strains were of the GH clade, 7% of the cases belonged to the GR clade, and 12% of the cases belonged to S, V, or G clades. One sample, acquired from a neonatal patient, presented with the highest viral RNA load of all patients evaluated at our center. Viral sequencing of this sample identified a SARS-CoV-2 spike variant, S:N679S. Analysis of data deposited in the GISAID global database of viral sequences shows the S:N679S variant is present in eight other sequenced samples within the US mid-Atlantic region. The similarity of the regional sequences suggests transmission and persistence of the SARS-CoV-2 variant within the Capitol region, raising the importance of increasing the frequency of SARS-CoV-2 genomic surveillance.IMPORTANCEA variant in the SARS-CoV-2 spike protein was identified in a febrile neonate who was hospitalized with COVID-19. This patient exhibited the highest viral RNA load of any COVID-19 patient tested at our center. Viral sequencing identified a spike protein variant, S:N679S, which is proximal to the cleavage site at residue 681. The SARS-CoV-2 surface spike is a protein trimer (three subunits) which serves as the key target for antibody therapies and vaccine development. Study of viral sequences from the GISAID database revealed eight related sequences from the US mid-Atlantic region. The identification of this variant in a very young patient, its critical location in the spike polyprotein, and the evidence that it has been detected in other patients in our region underscores the need for increased viral sequencing to monitor variant prevalence and emergence, which may have a direct impact on recommended public health measures and vaccination strategies.

The estimated SARS-CoV-2 seroprevalence in children was found to be 9.46% for the Washington Metropolitan area. Hispanic/Latinx individuals were found to have higher odds of seropositivity. While chronic medical conditions were not associated with having antibodies, previous fever and body aches were predictive symptoms.

Children require transfusion of blood components for a vast array of medical conditions, including acute hemorrhage, hematologic and nonhematologic malignancies, hemoglobinopathy, and allogeneic and autologous stem cell transplant. Evidence-based literature on pediatric transfusion practices is limited, particularly for non-red blood cell products, and many recommendations are extrapolated from studies in adult populations. Recognition of these knowledge gaps has led to increasing numbers of clinical trials focusing on children and establishment of pediatric transfusion working groups in recent years. This article reviews existing literature on pediatric transfusion therapy within the larger context of analogous data in adult populations.

Background: Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. The cause of these differences in presentation may relate to differences in the host response to infection between adults and children. We thus set out to measure the SARS-CoV-2-specific T cell (CST) response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection. Methods: CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay. Findings: Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses were significantly increased in adults versus children with uncomplicated SARS-CoV-2 infection (P=0.008), while children with MIS-C displayed a CST response that was similar to convalescent adults. Interpretation: Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults. Children with MIS-C have T cell immunity to SARS-CoV-2 that is similar to convalescent adults and greater than children with uncomplicated SARS-CoV-2, despite near uniform seropositivity. Funding: This study was funded by the Board of Visitors of Children’s National Hospital, the Connor Family Foundation, the Katzen Foundation, the National Institute of Allergy and Infectious Diseases, and the National Institute of Dental and Craniofacial Research. Declaration of Interest: C.M.B. is a co-founder and on the scientific advisory boards for Catamaran Bio and Mana Therapeutics with stock and/or ownership, is on the Board of Directors for Caballeta Bio with stock options and has stock in Neximmune and Repertoire Immune Medicines. M.D.K. is on a scientific advisory panel for Enzyvant. The other authors declare that there are no conflicts of interest. Ethical Approval: Peripheral blood mononuclear cells (PBMCs) were obtained from participants recruited from Children’s National Hospital (Washington, DC) and the National Institutes of Health under informed consent approved by the Institutional Review Board of both institutions in accordance with the Declaration of Helsinki.

Background:Blood transfusion is lifesaving for patients experiencing acute blood loss and severe anemia. In low- and middle-income countries (LMIC), availability of blood products impairs timely blood transfusion. A transfusion service (TS) is a clinical laboratory preparing blood products for patients. TS capabilities at the hospital level may contribute to preventable patient outcomes. We sought to learn more about the practices, capabilities, and challenges of TSs in LMIC . Materials and Methods: A cross-sectional survey explored hospital-level TS access to blood supplies, testing methods, policies, and structure. Surveys were administered in English, Spanish, French, and Russian, followed by a mixed methods analysis. Results: Responses (71) from 124 invitations comprised 50 TSs from 27 nations in low (4), low-middle (11), and upper-middle (12) income countries. Most LMIC TSs collected blood (36, 77%); only 11 (23%) relied on an external supply of blood products. Testing methods varied. The top reason for blood transfusion was adult anemia for non-malignant conditions (17, 15%). Blood transfusion delays (17, 57%) primarily involved inadequate blood supplies (15, 54%). Additional challenges involved educational access (8, 27%), financial models (4, 13%), or other barriers (8, 27%). Conclusions: This is the most-comprehensive survey into the status of hospital TSs in LMIC. Availability of blood products remains a dominant problem, requiring TSs to generate the facility’s blood supply. Blood shortages effect delays that are rarely reported as a patient-specific adverse event. Continued education and multi-disciplinary transfusion approaches were lacking. Safe and available blood transfusion extends beyond the TS, to governments and society. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The Children’s National Health System IRB provided ethical review for the protection of human subjects.

The interaction between thymocytes and thymic epithelial cells (TEC) in the thymus is critical for the correct function and maturation of both cell populations and for the development of a diverse repertoire of non-self-reactive T-cell lymphocytes. Limited information is available on lympho-stromal crosstalk in the thymus of patients carrying thymic defects. We have previously shown that thymic tissues from DiGeorge syndrome (DGS) and Down syndrome (DS) patients have alterations in architecture and TEC composition, leading to altered T-cell development. Based on these results, we are performing single cell RNAseq (scRNAseq) to explore the transcriptional landscape of both stromal and hematopoietic components in the human thymus. Thanks to a collaboration with the pediatric cardiothoracic surgery center at the Children’s National Medical Center in Washington D.C., we have access to discarded thymic samples obtained from pediatric patients with partial DGS and DS, and from patients without immune defects. Preliminary results of scRNAseq analysis comparing tissues from normal donors and DS patients revealed a different distribution of cell subsets in both hematopoietic and stromal compartments, with several pathways differentially regulated, such as stress and metabolic processes. Additionally, we established a collaboration with the Thoracic and Gastrointestinal Malignancies Branch at the National Cancer Institute and are evaluating samples obtained from resected thymic epithelial tumors. Integration of data obtained from normal and diseased thymic tissue will provide novel insights into the function and development of the human thymus that could be helpful in the clinical management of patients with thymic defects. This research was supported by the Intramural Research Programs of the NIAID and the NCI (Center for Cancer Research), NIH

Background We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada. Study design and methods An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions. Results The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56). Conclusion There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety.

BACKGROUND: Blood donors of African origin are under-represented in high-income Western countries, while their extended blood types closely match chronic transfusion patients with similar ancestral backgrounds. To prevent alloimunisation, it is important to recruit and retain more African blood donors. The aim of this study was to gain insight into blood donation barriers and motivators of individuals of African origin, and to assess how these are associated with the intention to donate blood. MATERIALS AND METHODS: An online survey sample included 300 participants of sub-Saharan African, Afro-Surinamese and Afro-Caribbean origin living in the Netherlands. They ranked 25 barriers and 19 motivators on the level of impediment and facilitation in blood donation. We compared differences in barriers and motivators between ever- and never-donors and tested associations with the intention to donate blood using univariate and multivariate linear regression analyses, adjusted for gender, age, ethnicity, immigrant generation, educational level, and blood donation history. RESULTS: Receiving information about the donation procedure was a highly ranked motivator especially among never-donors (50%) and was positively associated with the intention to donate (p

This cohort study compares the clinical features of coronavirus disease 2019 (COVID-19) with those of influenza A and B in US children., Key Points Question What are the similarities and differences in clinical features between coronavirus disease 2019 (COVID-19) and seasonal influenza in US children? Findings In this cohort study of 315 children with COVID-19 and 1402 children with seasonal influenza, there were no statistically significant differences in the rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use between the 2 groups. More patients with COVID-19 than with seasonal influenza reported fever, diarrhea or vomiting, headache, body ache, or chest pain at the time of diagnosis. Meaning The findings suggest that prevention of both COVID-19 and seasonal influenza in US children is prudent and urgent for the well-being of this population., Importance Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children’s National Hospital in the District of Columbia. Exposures COVID-19 or influenza A or B. Main Outcomes and Measures Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis.