How do we build a comprehensive Vein-to-Vein (V2V) database for conduct of observational studies in transfusion medicine? Demonstrated with the Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric V2V database protocol.

BACKGROUND: The Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) is the fourth iteration of the National Heart, Lung, and Blood Institute's REDS program and includes a focus on pediatric populations. The REDS-IV-P Vein-to-Vein (V2V) database encompasses linked information from blood donors, blood components, and patients to facilitate studies in transfusion medicine. STUDY DESIGN AND METHODS: The V2V database is an Observational Medical Outcomes Partnership Common Data Model database. The study period is April 1, 2019 through December 31, 2023. Data from all donors and donations at participating blood centers, all blood components derived from the donations, and all inpatient visits and selected outpatient visits at participating hospitals are included. The database captures all information within patient data domains not restricting data to a preselected subset of medical records. RESULTS: The V2V database contains data from 7 blood centers and 22 hospitals. We project the database will have over 2 billion pieces of information from 1.3 million patients with 20.6 million healthcare encounters. The database will include data on approximately 1 million transfused units and 2.3 million donors with approximately 6.8 million donation visits. CONCLUSION: The REDS-IV-P V2V database is a comprehensive database with data from millions of blood donors, blood components, and patients. A diverse set of data from the encounters are included in the database such that emerging questions can likely be addressed. The Observational Medical Outcomes Partnership Common Data Model is an efficient, flexible, and increasingly used common data model. The final de-identified database will be publicly available.

In hospitalized patients undergoing therapeutic plasma exchange, major bleeding prevalence depends on the bleeding definition: An analysis of The Recipient Epidemiology and Donor Evaluation Study-III.

BACKGROUND: Major bleeding in patients undergoing therapeutic plasma exchange (TPE) has been studied in large databases; but without standardizing bleeding definitions. Therefore, we used standardized definitions to evaluate major bleeding in hospitalized patients undergoing TPE using public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). STUDY DESIGN AND METHODS: In a retrospective cross-sectional analysis, we identified TPE-treated adults in a first inpatient encounter. We evaluated major bleeding prevalence using (1) International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) codes, (2) packed red blood cell (PRBC) transfusion, or (3) hemoglobin (Hgb) decline. Patients with major bleeding prior to their first TPE were excluded from the analysis. RESULTS: Among 779 patients undergoing TPE, major bleeding by at least one of the three bleeding definitions occurred in 135 patients (17.3%). For each of the ICD/CPT, PRBC, and Hgb definitions, the prevalence of major bleeding was 2.8% (n = 31), 7.4% (n = 81), and 5.4% (n = 59), respectively. Only 3.7% of bleeds (5/135) were captured by all three definitions and 19.3% (26/135) exclusively by any two pairwise definitions. The addition of PRBC transfusion and Hgb decline to ICD/CPT code definitions increased bleeding prevalence threefold. CONCLUSION: Among hospitalized adults undergoing TPE in the REDS-III study, the prevalence of major bleeding was 17.3%. The addition of PRBC and Hgb decline to ICD codes increased bleeding prevalence threefold. Future studies are needed to develop validated models that identify patients at risk for major bleeding during TPE.

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.

Antibody Titers in Transfusion Medicine: A Critical Reevaluation of Testing Accuracy, Reliability, and Clinical Use.

CONTEXT.­: Substantial variability between different antibody titration methods has been identified since the development and introduction of the uniform procedure in 2008. OBJECTIVE.­: To determine whether more recent methods or techniques decrease interlaboratory and intralaboratory variation measured using proficiency testing. DESIGN.­: Proficiency test data for antibody titration between 2014 and 2018 were obtained from the College of American Pathologists. Interlaboratory and intralaboratory variations were compared by analyzing the distribution of titer results by method and phase, comparing the results against the supplier's quality control titer, and by evaluating the distribution of paired titer results when each laboratory received a sample with the same titer twice. RESULTS.­: A total of 1337 laboratories participated in the antibody titer proficiency test during the study period. Only 54.1% (5874 of 10 852) of anti-D and 63.4% (3603 of 5680) of anti-A reported responses were within 1 titer of the supplier's intended result. Review of the agreement between laboratories of the same methodology found that 78.4% (3139 of 4004) for anti-A and 89.0% (9655 of 10 852) of laboratory responses for anti-D fell within 1 titer of the mode response. When provided with 2 consecutive samples of the same titer (anti-D titer: 16), 85% (367 of 434) of laboratories using the uniform procedure and 80% (458 of 576) using the other method reported a titer difference of 1 or less. CONCLUSIONS.­: Despite advances, interlaboratory and intralaboratory variance for this assay remains high in comparison with the strong reliance on titer results in clinical practice. There needs to be a reevaluation of the role of this test in clinical decision-making.

Obstetric and Newborn Weak D-Phenotype RBC Testing and Rh Immune Globulin Management Recommendations: Lessons From a Blinded Specimen-Testing Survey of 81 Transfusion Services.

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.

Hypoxic storage of donor red cells preserves deformability after exposure to plasma from adults with sickle cell disease.

BACKGROUND: Red cell (RBC) transfusions are beneficial for patients with sickle cell disease (SCD), but ex vivo studies suggest that inflamed plasma from patients with SCD during crises may damage these RBCs, diminishing their potential efficacy. The hypoxic storage of RBCs may improve transfusion efficacy by minimizing the storage lesion. We tested the hypotheses that (1) The donor RBCs exposed to the plasma of patients in crisis would have lower deformability and higher hemolysis than those exposed to non-crisis plasma, and (2) hypoxic storage, compared to standard storage, of donor RBCs could preserve deformability and reduce hemolysis. STUDY DESIGN AND METHODS: 18 SCD plasma samples from patients who had severe acute-phase symptoms (A-plasma; n = 9) or were at a steady-state (S = plasma; n = 9) were incubated with 16 RBC samples from eight units that were stored either under conventional(CRBC) or hypoxic(HRBC) conditions. Hemolysis and microcapillary deformability assays of these RBCs were analyzed using linear mixed-effect models after each sample was incubated in patient plasma overnight at 37°C RESULTS: Relative deformability was 0.036 higher (p < 0.0001) in HRBC pairs compared to CRBC pairs regardless of plasma type. Mean donor RBC hemolysis was 0.33% higher after incubation with A-plasma compared to S-plasma either with HRBC or CRBC (p = 0.04). HRBCs incubated with steady-state patient plasma demonstrated the highest deformability and lowest hemolysis. CONCLUSION: Hypoxic storage significantly influenced RBC deformability. Patient condition significantly influenced post-incubation hemolysis. Together, HRBCs in steady-state plasma maximized donor red cell ex vivo function and survival.

Genotyping and the Future of Transfusion in Sickle Cell Disease.

Patients with sickle cell disease (SCD) have a high rate of red cell alloimmunization, which increases morbidity and mortality. Reasons for this susceptibility are multifactorial, but differences in antigen frequency between donors and recipients are one of the modifiable risk factors. Here, we evaluate the benefits of red cell molecular antigen-typing for both patients with SCD and their donors and describe how results from these critical tests could be used to enhance patient safety.

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.

Hospital transfusion service operations during the SARS-CoV-2 pandemic: Lessons learned from the AABB hospital survey in preparation for the next infectious disease outbreak.

BACKGROUND: The SARS-CoV-2 pandemic disrupted hospital operations, affected the blood supply, and challenged the health care system to develop new therapeutic options, including convalescent plasma (CCP). The aim of this study is to describe and analyze blood supply fluctuations and the use of convalescent plasma in 2020. METHODS: AABB distributed a weekly and biweekly questionnaire through email to hospital-based members (HBM). RESULTS: The survey was sent to 887 HBM with 479 unique respondents, most of the hospitals served pediatric and adult patients, and all states of the country participated, except Idaho and Vermont. Fifty four percent of HBM reported increased wastage in the early phase of the pandemic (May), which decreased to 4% by the end of June and throughout the rest of the year. The majority of HBM reported receiving alerts from their blood suppliers reporting blood shortages throughout the year. During March and April, only 12% of HBM were performing elective surgical procedures. The top reasons to delay procedures were: bed availability (28%); COVID-19 caseload (23%; and blood availability (19%). By mid-April, 42% HBM had transfused CCP and reported >24 h delay in getting the units; the vast majority obtained CCP using the Expanded Access Protocol, and later, the Emergency Use Authorization. HBM consistently prioritized the most severe patients to receive CCP, but the proportion of severely ill recipients fell from 52% to 37% between May and October, with an increase from 5% to 21% of HBM providing CCP transfusion early in the course of the disease. DISCUSSION: Blood utilization and availability fluctuated during the pandemic. The fluctuations appeared to be related to the number of COVID-19 in the community. The use and regulatory landscape of CCP rapidly evolved over the first 8 months of the pandemic.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III).

BACKGROUND: To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. STUDY DESIGN AND METHODS: This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. RESULTS: A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5 g/dl (10-90th percentile: 6.4-8.8 g/dl), with 45.7% of transfusions being given at 7 to <8 g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. DISCUSSION: Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Transfusion Practices in Pediatric Cardiac Surgery Requiring Cardiopulmonary Bypass: A Secondary Analysis of a Clinical Database.

OBJECTIVES: To describe blood component usage in transfused children with congenital heart disease undergoing cardiopulmonary bypass surgery across perioperative settings and diagnostic categories. DESIGN: Datasets from U.S. hospitals participating in the National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III were analyzed. SETTING: Inpatient admissions from three U.S. hospitals from 2013 to 2016. PATIENTS: Transfused children with congenital heart disease undergoing single ventricular, biventricular surgery, extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight hundred eighty-two transfused patients were included. Most of the 185 children with single ventricular surgery received multiple blood products: 81% RBCs, 79% platelets, 86% plasma, and 56% cryoprecipitate. In the 678 patients undergoing biventricular surgery, 85% were transfused plasma, 75% platelets, 74% RBCs, and 48% cryoprecipitate. All 19 patients on extracorporeal membrane oxygenation were transfused RBCs, plasma, and cryoprecipitate, and 18 were transfused platelets. Intraoperatively, patients commonly received all three components, while postoperative transfusions were predominantly single blood components. Pretransfusion hemoglobin values were normal/low-normal for age for all phases of care for single ventricular surgery (median hemoglobin 13.2-13.5 g/dL). Pretransfusion hemoglobin values for biventricular surgeries were higher intraoperatively compared with other timing (12.2 g/dL vs 11.2 preoperative and postoperative; p < 0.0001). Plasma transfusions for all patients were associated with a near normal international normalized ratio: single ventricular surgeries median international normalized ratio was 1.3 postoperative versus 1.8 intraoperative and biventricular surgeries median international normalized ratio was 1.1 intraoperative versus 1.7 postoperative. Intraoperative platelet transfusions with biventricular surgeries had higher median platelet count compared with postoperative pretransfusion platelet count (244 × 109/L intraoperative vs 69 × 109/L postoperative). CONCLUSIONS: Children with congenital heart disease undergoing cardiopulmonary bypass surgery are transfused many blood components both intraoperatively and postoperatively. Multiple blood components are transfused intraoperatively at seemingly normal/low-normal pretransfusion values. Pediatric evidence guiding blood component transfusion in this population at high risk of bleeding and with limited physiologic reserve is needed to advance safe and effective blood conservation practices.

Human leukocyte antigen (HLA)-incompatible mean fluorescence intensity-selected platelet products have corrected count increments similar to HLA antigen-matched platelets.

BACKGROUND: Donor specific antibody sum mean fluorescence intensity (MFI) values have been successfully used in transplant medicine to assess risk for organ rejection. However, little is known regarding whether MFI values could be similarly used to aid in platelet product selection. We have developed a novel protocol where MFI values are used to offer human leukocyte antigen (HLA)-incompatible platelet products when HLA antigen-matched products are not available. We aimed to evaluate the efficacy of this protocol. METHODS: We performed a 4-year retrospective chart review for all patients who received at least one MFI-selected platelet product. A corrected count increment (CCI) was calculated for each transfusion event. A mixed effects model was used to investigate the association between CCIs for MFI-selected, HLA antigen matched, and random donor platelet transfusions. A random effects expectation-maximization regression tree was used to define the extent to which other patient variables, such as age, sex, and diagnosis impacted the CCI for each platelet transfusion. RESULTS: Twenty highly HLA alloimmunized patients received a total of 591 platelets. MFI-selected platelet (low MFI) transfusions had a significantly higher median CCI 0-6 hour post-transfusion (13,559, interquartile range [IQR]: 8275-18,736) compared to random donor platelets (2121, IQR: 0-10,368, p < 0.0001). There was no significant difference in median CCI between HLA antigen matched and MFI selected platelet transfusions (p = 0.2). Mixed effects and regression modeling revealed that MFI-selected platelet products had a significantly higher CCI than non-matched platelets, even when accounting for other significant patient variables. CONCLUSION: MFI-selected HLA-incompatible platelet products could provide a comparable alternative to traditional HLA antigen-matched platelet products.

Hematologic and systemic metabolic alterations due to Mediterranean class II G6PD deficiency in mice.

Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is the single most common enzymopathy, present in approximately 400 million humans (approximately 5%). Its prevalence is hypothesized to be due to conferring resistance to malaria. However, G6PD deficiency also results in hemolytic sequelae from oxidant stress. Moreover, G6PD deficiency is associated with kidney disease, diabetes, pulmonary hypertension, immunological defects, and neurodegenerative diseases. To date, the only available mouse models have decreased levels of WT stable G6PD caused by promoter mutations. However, human G6PD mutations are missense mutations that result in decreased enzymatic stability. As such, this results in very low activity in red blood cells (RBCs) that cannot synthesize new protein. To generate a more accurate model, the human sequence for a severe form of G6PD deficiency, Med(-), was knocked into the murine G6PD locus. As predicted, G6PD levels were extremely low in RBCs, and deficient mice had increased hemolytic sequelae to oxidant stress. Nonerythroid organs had metabolic changes consistent with mild G6PD deficiency, consistent with what has been observed in humans. Juxtaposition of G6PD-deficient and WT mice revealed altered lipid metabolism in multiple organ systems. Together, these findings both establish a mouse model of G6PD deficiency that more accurately reflects human G6PD deficiency and advance our basic understanding of altered metabolism in this setting.

Transfusion practices in a large cohort of hospitalized children.

BACKGROUND: While previous studies have described the use of blood components in subsets of children, such as the critically ill, little is known about transfusion practices in hospitalized children across all departments and diagnostic categories. We sought to describe the utilization of red blood cell, platelet, plasma, and cryoprecipitate transfusions across hospital settings and diagnostic categories in a large cohort of hospitalized children. STUDY DESIGN AND METHODS: The public datasets from 11 US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) were accessed. All nonbirth inpatient encounters of children 0-18 years of age from 2013 to 2016 were included. RESULTS: 61,770 inpatient encounters from 41,943 unique patients were analyzed. Nine percent of encounters involved the transfusion of at least one blood component. RBC transfusions were most common (7.5%), followed by platelets (3.9%), plasma (2.5%), and cryoprecipitate (0.9%). Children undergoing cardiopulmonary bypass were most likely to be transfused. For the entire cohort, the median (interquartile range) pretransfusion laboratory values were as follows: hemoglobin, 7.9 g/dl (7.1-10.4 g/dl); platelet count, 27 × 109 cells/L (14-54 × 109 cells/L); and international normalized ratio was 1.6 (1.4-2.0). Recipient age differences were observed in the frequency of RBC irradiation (95% in infants, 67% in children, p < .001) and storage duration of RBC transfusions (median storage duration of 12 [8-17] days in infants and 20 [12-29] days in children, p < .001). CONCLUSION: Based on a cohort of patients from 2013 to 2016, the transfusion of blood components is relatively common in the care of hospitalized children. The frequency of transfusion across all pediatric hospital settings, especially in children undergoing cardiopulmonary bypass, highlights the opportunities for the development of institutional transfusion guidelines and patient blood management initiatives.

Variation in Neonatal Transfusion Practice.

OBJECTIVE: To estimate the incidence of blood product transfusion, including red blood cells, platelets, and plasma, and characterize pretransfusion hematologic values for infants during their initial hospitalization after birth. STUDY DESIGN: Retrospective cohort study using data from 7 geographically diverse US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) from 2013 to 2016. Pretransfusion hematologic values were evaluated closest to each transfusion and no more than 24 hours beforehand. RESULTS: Data from 60 243 infants were evaluated. The incidence of any transfusion differed by gestational age (P < .0001), with 80% (95% CI 76%-84%) transfused at <27 weeks of gestation (n = 329) and 0.5% (95% CI 0.5%-0.6%) transfused at ≥37 weeks of gestation (n = 53 919). The median pretransfusion hemoglobin was 11.2 g/dL (10th-90th percentile 8.8-14.1) for the entire cohort, ranging from 10.5 g/dL (8.8-12.3) for infants born extremely preterm at <27 weeks of gestation to 13.0 g/dL (10.5-15.5) for infants born at term. The median pretransfusion platelet count (×109/L) was 71 (10th-90th percentile 26-135) for the entire cohort, and was >45 for all gestational age groups examined. The median pretransfusion international normalized ratio for the entire cohort was 1.7 (10th-90th percentile 1.2-2.8). CONCLUSIONS: There is wide variability in pretransfusion hemoglobin, platelet count, and international normalized ratio values for neonatal transfusions. Our findings suggest that a large proportion of neonatal transfusions in the US are administered at thresholds greater than supported by the best-available evidence and highlight an opportunity for improved patient blood management.

Heterogeneity in Approaches for Switching From Universal to Patient ABO Type-Specific Blood Components During Massive Hemorrhage.

CONTEXT.­: ABO mistransfusions are rare and potentially fatal events. Protocols are required by regulatory agencies to minimize this risk to patients, but how these are applied in the context of massive transfusion protocols (MTPs) is not specifically defined. OBJECTIVE.­: To evaluate the approaches used by transfusion services for switching from universally compatible to patient ABO type-specific blood components during massive hemorrhage. DESIGN.­: We added 1 supplemental multiple-choice question to address the study objective to the 2019 College of American Pathologists proficiency test J-survey (J-A 2019). We also reviewed the available literature regarding this topic. RESULTS.­: A total of 881 laboratories responded to the supplemental question. Approximately 80% (704 of 881) reported a policy for ABO-type switching during an MTP. Policies varied considerably between responding laboratories, but most (384 of 704, 55%) required 2 ABO types to match before switching from universal to recipient-specific blood components. Additional safety measures used in a minority of these protocols included reaction strength criteria (103 of 704, 15%), on-call medical director approval (41 0f 704, 5.8%), universal red cell unit number limits (12 of 704, 1.7%), or the presence of a mixed field (3 of 704, 0.4%). CONCLUSIONS.­: This survey reveals that significant heterogeneity exists regarding the available approaches for ABO-type switching during an MTP. Specific expert guidance regarding this issue is very limited, and best practices have not yet been established or rigorously investigated.

Chronic Pain Does Not Impact Baseline Circulating Cytokine Levels in Adults with Sickle Cell Disease.

Chronic pain affects 50% of adults with sickle cell disease (SCD). Although inflammation is thought to contribute to the pathogenesis of chronic pain, no studies have examined the differences in circulating cytokines between patients with SCD with and without chronic pain. We performed an observational cohort study using blood and urine samples from adults with SCD with and without chronic pain at their usual state of health. We tested the hypothesis that, compared to those without chronic pain, those with chronic pain would have significantly higher baseline circulating proinflammatory cytokines. A total of 61 adults with SCD, 40 with chronic pain and 21 without chronic pain were tested. When SCD patients with chronic pain were compared to those without chronic pain, no significant differences in cytokine levels were noted. The variables most associated with the diagnosis of chronic pain in this population were opioid dose and subject age.

ZOOMICS: Comparative Metabolomics of Red Blood Cells From Old World Monkeys and Humans.

As part of the ZOOMICS project, we set out to investigate common and diverging metabolic traits in the blood metabolome across various species by taking advantage of recent developments in high-throughput metabolomics. Here we provide the first comparative metabolomics analysis of fresh and stored human (n = 21, 10 males, 11 females), olive baboon (n = 20), and rhesus macaque (n = 20) red blood cells at baseline and upon 42 days of storage under blood bank conditions. The results indicated similarities and differences across species, which ultimately resulted in a differential propensity to undergo morphological alterations and lyse as a function of the duration of refrigerated storage. Focusing on purine oxidation, carboxylic acid, fatty acid, and arginine metabolism further highlighted species-specific metabolic wiring. For example, through a combination of steady state measurements and 13C6 15N4-arginine tracing experiments, we report an increase in arginine catabolism into ornithine in humans, suggestive of species-specific arginase 1 activity and nitric oxide synthesis-an observation that may impact the translatability of cardiovascular disease studies carried out in non-human primates (NHPs). Finally, we correlated metabolic measurements to storage-induced morphological alterations via scanning electron microscopy and hemolysis, which were significantly lower in human red cells compared to both NHPs.

Red cell exchange for patients with sickle cell disease: an international survey of current practices.

INTRODUCTION: Red cell exchange (RCE) therapy is increasingly used to treat patients with acute or chronic manifestations of sickle cell disease (SCD). However, little is known regarding the most safe and effective practice parameters associated with this particular therapy. METHODS: A SCD subcommittee of members of the American Society for Apheresis (ASFA) developed a 122-question survey and administered it via email to other ASFA members. The survey inquired about clinical indications for treatment, practice patterns, and transfusion policies for RCE when used for patients with SCD. RESULTS: Ninety-nine distinct institutions completed the survey. Twenty-one (21%) were from outside of the US. Twenty-two (22%) provided chronic transfusion therapy to >10 patients, and both adult (25%) and pediatric-focused services (20%) were represented. Common acute indications for RCE included acute chest syndrome, acute ischemic stroke, and pre-surgical prophylaxis. Common chronic indications included primary stroke prophylaxis, secondary stroke prophylaxis, and recurrent acute chest syndrome. Respondents most commonly set a post-RCE treatment target of 30% for the hematocrit and hemoglobin S levels, regardless of the therapeutic indication. Units for RCE were phenotypically matched in 95% of cases. About 40% of respondents reported using isovolemic hemodilution. CONCLUSIONS: This survey solicited the current practice variations in RCE from a diverse range of practice sites. Many sites reported similar practice patterns and challenges but some variations emerged. To our knowledge, this survey represents the largest and most in-depth investigation of the use of RCE for patients with SCD, and could inform future studies in the field.