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Background: The Association for the Advancement of Blood and Biotherapies guidelines recommend the use of high-titer COVID-19 convalescent plasma (CCP) for patients with SARS-CoV-2 at high risk of disease progression, including those who are immunocompromised. We hypothesized that conventional plasma units have comparable neutralizing antibody levels to CCP., Study Design and Methods: Conventional plasma and CCP units were obtained from blood suppliers. Quantitatively measured antibodies to SARS-CoV-2 were assessed using the MesoScale Discovery multiplex electrochemiluminescence immunoassay. Binding antibody distributions were compared with Wilcoxon rank-sum tests. SARS-CoV-2 neutralizing antibodies were analyzed using the GeneScript ELISA-based neutralization assay. The proportion of conventional and CCP units with a percent signal inhibition of ≥80% (as defined by the United States Food and Drug Administration for CCP in 2021) and exact binomial confidence intervals (CIs) were calculated., Results: Among 218 conventional plasma units and 74 CCP units collected between September 2023 and July 2024, the distribution of total antibody binding levels largely overlapped between conventional plasma and CCP, though statistically significant differences in median nucleocapsid and spike Omicron variant concentrations were observed. Median percent signal neutralization was 97.5% (range 3.4%-98.6%) among conventional plasma units and 97.7% (range 95.4%-98.6%) among CCP units. For conventional plasma, 95.0% (95% CI = 91.2%-97.5%) met the neutralization antibody threshold for high-titer CCP. For CCP, 100% (95% CI = 95.1%-100.0%) met the neutralization threshold for high-titer CCP., Conclusion: Conventional plasma units demonstrate similar median antibody concentration to CCP units. In countries or regions where licensed CCP is unavailable and titers are unknown, transfusion of multiple conventional plasma units may be of clinical utility., (© 2025 AABB.)

Background: Splitting apheresis platelet (PLT) units increase available inventory during shortages. The impact of prolonged storage in gas-impermeable aliquot bags on PLT quality in vitro and transfusion outcomes in patients remains uncertain., Study Design and Methods: We assessed in vitro PLT quality and thromboelastography (TEG) in PLTs stored for 8 or 24 h in aliquot bags compared with baseline (T0). Retrospective assessment of response (PLT increment and corrected count increment (CCI)) was conducted among adults (≥18 years) transfused with split platelet units from January 2021 to June 2022., Results: No differences were observed in PLT and white blood cell (WBC) counts, mean platelet volume, or TEG parameters during storage, except for an increase in TEG R time (mean ± SD) at 24 h (6.1 ± 0.5 min) compared to T0 (4.4 ± 0.8 min), p = 0.0031 one-way ANOVA. Eighty-one patients were transfused 119 split units with a median [IQR] PLT yield of 2.1 × 10 11 [1.9 × 10 11 to 2.3 × 10 11 ] and storage duration of 1.6[0.7-9.1] h. The overall median PLT count increment was 6.0 × 10 3 /uL and CCI was 5.0 × 10 3 , correlating negatively with split unit storage duration (Spearman rho = -0.218, p = 0.017). Compared with split transfusions of pathogen-reduced (PR) PLTs, non-PR splits were associated with higher median platelet count increments (7.0 × 10 3 /μL vs. 4.0 × 10 3 /μL, p = 0.0263 Mann-Whitney U) and higher CCIs (6.5 × 10 3 vs. 3.9 × 10 3 , p = 0.0116 Mann-Whitney U) despite no differences in PLT yields (2.1 × 10 11 /μL vs. 2.1 × 10 11 /μL)., Discussion: Storing PLTs in aliquot bags for 8 or 24 h does not adversely affect their quality in vitro. Splitting apheresis PLTs are feasible for adult transfusions during shortages. It may be advisable to prioritize non-PR PLTs for splitting given improved patient responses., (© 2024 AABB.)

Background: Many children with sickle cell disease (SCD) who suffer a stroke receive chronic transfusion therapy (CTT) indefinitely; however, their adulthood neurologic outcomes have not been reported. Understanding these outcomes is critical to inform decisions regarding curative therapy in childhood., Study Design and Methods: In this retrospective study, we described a cohort of adults with SCD and a history of childhood stroke who received care at a single center and compared their outcomes with matched subjects without childhood stroke using chi 2 and Mann-Whitney U tests., Results: Of 42 subjects with childhood stroke, all received CTT for secondary stroke prophylaxis. Five (11%) developed recurrent stroke. The rate of stroke was similar in subjects with and without childhood stroke (0.7 vs. 1.1 per 100 person·years, p = .63). Both cohorts exhibited evidence of iron overload (median ferritin 2227 vs. 1409 ng/dL, p = .10) and alloimmunization (45% vs. 45%, p = 1.0), despite receiving care in a comprehensive SCD program., Discussion: For adults with SCD who had a childhood stroke, our results suggest CTT returns the risk of stroke to that of age-matched stroke naïve patients with SCD., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloantibody-mediated destruction of fetal/neonatal red blood cells (RBCs). While the pathophysiology has been well-characterized, the clinical and laboratory monitoring practices are inconsistent., Methods: We surveyed 103 US institutions to characterize laboratory testing practices for individuals with fetuses at risk of HDFN. Questions included antibody testing and titration methodologies, the use of critical titers, paternal and cell-free fetal DNA testing, and result reporting and documentation practices., Results: The response rate was 44% (45/103). Most respondents (96%, 43/45) assess maternal antibody titers, primarily using conventional tube-based methods only (79%, 34/43). Among respondents, 51% (23/45) rescreen all individuals for antibodies in the third trimester, and 60% (27/45) perform paternal RBC antigen testing. A minority (27%, 12/45) utilize cell-free fetal DNA (cffDNA) testing to predict fetal antigen status. Maternal antibody titers are performed even when the fetus is not considered to be at risk of HDFN based on cffDNA or paternal RBC antigen testing at 23% (10/43) of sites that assess titers., Discussion: There is heterogeneity across US institutions regarding the testing, monitoring, and reporting practices for pregnant individuals with fetuses at risk of HDFN, including the use of antibody titers in screening and monitoring programs, the use of paternal RBC antigen testing and cffDNA, and documentation of fetal antigen results. Standardization of laboratory testing protocols and closer collaboration between the blood bank and transfusion medicine service and the obstetric/maternal-fetal medicine service are needed., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: The data to support chronic automated red cell exchange (RCE) in sickle cell disease (SCD) outside of stroke prevention, is limited, especially in adults., Study Design and Methods: A retrospective analysis was conducted of patients with SCD who were referred for chronic RCE at our institution over a 10-year period. Data that were evaluated included patient demographics, referral indications, and procedural details (e.g., vascular access, adverse events, etc.). In a subanalysis, the number of annual acute care encounters during 3 years of chronic RCE was compared with that in the year preceding the first RCE., Results: A total of 164 patients were referred for chronic RCE: median age was 28 years (interquartile range [IQR] = 22-36) at referral and 60% were female. Seventy (42.6%) were naïve to chronic transfusion (simple or RCE) prior to referral. The leading indications for referral were refractory pain (73/164, 44.5%) and iron overload (57/164, 34.7%). A total of 5090 procedures occurred during the study period (median = 19, IQR = 5-45). Of the 138 patients who had central vascular access, 8 (6%) and 16 (12%) had ≥1 central-line-related thrombosis and/or infection, respectively. Of those who were not RBC alloimmunized at initiation of RCE, 12/105 (11.4%) developed new antibodies during chronic RCE. In those 30 patients who were adherent to therapy for 3 years, there was no significant difference in acute care encounters following initiation of RCE., Conclusion: Prospective clinical trials are needed to determine which patients are most likely to benefit from chronic RCE and refine selection accordingly., (© 2024 AABB.)

Background: Washing red blood cell (RBC) units mitigates severe allergic transfusion reactions. However, washing reduces the time to expiration and the effective dose. Automated washing is time- and labor-intensive. A shortage of cell processor tubing sets prompted review of medical necessity for washed RBC for patients previously thought to require washing., Study Design and Methods: A single-center, retrospective study investigated discontinuing wash RBC protocols in chronically transfused adults. In select patients with prior requirements for washing, due to a history of allergic transfusion reactions, trials of unwashed transfusions were performed. Patient demographic, clinical, laboratory, and transfusion data were compiled. The per-unit washing cost was the sum of the tubing set, saline, and technical labor costs., Results: Fifteen patients (median age 34 years interquartile range [IQR] 23-53 years, 46.7% female) were evaluated. These patients had been transfused with a median of 531 washed RBC units (IQR 244-1066) per patient over 12 years (IQR 5-18 years), most commonly for recurrent, non-severe allergic reactions. There were no transfusion reactions with unwashed RBCs aside from one patient with one episode of pruritus and another with recurrent pruritus, which was typical even with washed RBC. We decreased the mean number of washed RBC units per month by 72.9% (104 ± 10 vs. 28.2 ± 25.2; p < .0001) and saved US $100.25 per RBC unit., Conclusion: Washing of RBCs may be safely reconsidered in chronically transfused patients without a history of anaphylaxis. Washing should be implemented judiciously due to potential lack of necessity and logistical/operational challenges., (© 2023 AABB.)

Background: Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO)., Study Design and Methods: We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT., Results: Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange., Conclusion: Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange., (© 2023 AABB.)

Background: Intrauterine transfusion (IUT) is an invasive but critical and potentially life-saving intervention for severe fetal anemia with demonstrated improvement in outcomes. The fetus is vulnerable to hemodynamic alterations and transfusion-related adverse events; therefore, special consideration must be given to blood component selection and modification. There is widespread IUT practice variability, and existing guidance primarily relies on expert opinion and single center experiences., Study Design and Methods: Experts in Maternal Fetal Medicine, Pediatric Hematology, and Transfusion Medicine from centers across the United States, collectively performing about 120 IUT annually, offer a multidisciplinary perspective on the performance of IUT and preparation of blood components. This perspective includes strategies for identifying an at-risk fetus, communicating between disciplines, determining the necessary blood volume, selecting and processing blood components, documenting the procedure in medical record, and managing the neonate., Results: Identifying an at-risk fetus relies on review of the clinical history, non-invasive monitoring, and laboratory evaluation. We recommend the use of relatively fresh, group O, cytomegalovirus-safe, freshly irradiated, red blood cells (RBC) that are Hemoglobin S negative and antigen-negative for any maternal antibody, if indicated. These RBC units should be concentrated to remove additives and increase the hematocrit thus minimizing fluctuations in fetal volume status. The units intended for IUT should be labeled clearly and the documentation of transfusion differentiated in the maternal medical record., Discussion: An awareness of the technical, logistical, and regulatory considerations for IUT performance will facilitate improved communication and patient care, especially when rare units of RBC are required., (© 2023 AABB.)

Background: Collecting a patient's blood in a correctly labeled pretransfusion specimen tube is essential for accurate ABO typing and safe transfusion. Noncompliance with specimen collection procedures can lead to wrong blood in tube (WBIT) incidents with potentially fatal consequences. Recent WBIT events inspired the investigation of how various institutions currently reduce the risk of these errors and ensure accurate ABO typing of patient samples., Materials and Methods: This article describes the techniques employed at various institutions across the United States to mitigate the risk of misidentified pretransfusion patient specimens. Details and considerations for each of these measures are provided., Results: Several institutions require the order for an ABO confirmation specimen, if indicated, to be generated from the transfusion medicine (TM) laboratory. Others issue a dedicated collection tube that is available exclusively from the TM service. Many institutions employ barcoding for electronic positive patient identification. Some use a combination of these strategies, depending on the locations or service lines from which the specimens are collected., Conclusion: The description of various WBIT mitigation strategies will inform TM services on practices that may be effective at their respective institutions. Irrespective of the method(s) utilized, institutions should continue to monitor and mitigate specimen misidentification errors to promote sustained safe transfusion practices., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Prior to laboratory-based blood donor screening for Babesia, transfusion-transmitted babesiosis (TTB) was a leading infectious risk to the blood supply in the United States., Case Report: A 30-year-old man with sickle cell disease (SCD) who had been on a chronic automated red cell exchange (RCE) regimen since childhood, presented approximately 2 months after an RCE, with fever, neck pain, and photophobia. Meningitis was excluded, and he was discharged. He presented again 2 days later with persistent fever, chills, headache, fatigue, and loss of appetite., Results: On examination, the patient was febrile but hemodynamically stable. Intra-erythrocytic inclusions were identified on a peripheral blood smear (<0.5%). B. microti IgM and IgG titers were >1:320 (Reference <1:20) >1:1024 (Reference <1:64), respectively. B. microti was confirmed by nucleic acid testing. The patient lived in a Babesia endemic state but had no risk factors for tick-borne acquisition. Of the 65 units he received in the preceding 6 months, 58 had been screened for Babesia. One of the donors of the 7 untested units was B. microti seropositive (titer 1:128; Reference 1: 64). The donor was asymptomatic and resided in a state in which Babesia screening was not required. He reported traveling in the year before his donation., Conclusion: Although rare, TTB is still possible despite regional screening, underscoring the need for provider vigilance and education, especially in non-endemic areas. Patients with SCD are particularly vulnerable given their high frequency of transfusion and complex needs requiring blood procurement from states where Babesia screening is not mandatory., (© 2023 AABB.)

Background: A paucity of data exists about the current practice of fetal red blood cell (RBC) transfusion in the United States (US). This investigation describes intrauterine transfusion (IUT) RBC product selection and processing practices at different US institutions., Methods: A transfusion medicine and maternal-fetal medicine (MFM) team designed a survey to interrogate and characterize RBCs utilized for IUT. This survey was distributed to seventy US institutions with fetal treatment centers (October 2020-April 2021) identified through the NAFTNet (North American Fetal Therapy Network)., Results: Thirty-seven institutions responded (response rate 53%, 37/70), but five were excluded for not performing IUTs. Most (84%; 27/32) performed 1-24 IUTs annually; two performed >50 IUTs/year. Group O, Rh(D) negative RBC units were always used by 66% (21/32), and 75% (24/32) provided hemoconcentrated RBCs by washing (17/24) or dry packing (6/24). Overall, 66% (21/32) targeted a hematocrit ≥75%. Fifty percent provided both leukocyte-reduced and CMV-negative RBC units. Irradiation of RBC units was performed within 6 h of issue at 63% (20/32) of sites. Most (81%, 26/32) used RBC units at <7 days of age after collection, 56% (18/32) always provided washed RBC units, while 19% (6/32) issued washed RBC only if fresh units are unavailable. Implicated maternal RBC alloantibodies were matched for 78% (25/32) of the time. The transfused volume was universally determined by the MFMs., Discussion: Heterogeneity and lack of standardization exist in RBC product selection and special processing steps for IUTs in the US. Hence, the establishment of a consensus to standardize IUT protocols is needed., (© 2022 AABB.)

Background: Due to the national blood supply crisis caused by the COVID-19 pandemic, the American Society of Hematology proposed guidance to decrease blood utilization for sickle cell patients on chronic transfusion therapy (CTT). Little evidence exists to support the efficacy and safety of these blood conservation strategies., Study Design and Methods: Through retrospective analysis, we sought to describe outcomes following implementation of these recommendations in 58 adult sickle cell patients on chronic exchange transfusions. The strategies employed included: relaxing the goal fraction of cells remaining (FCR) to 30%-50%, utilizing depletion exchanges in select patients, and transitioning select patients to monthly simple transfusions. We compared hemoglobin S%, hemoglobin values, and other laboratory parameters, acute care visits, and red blood cell usage during the first year of the COVID-19 pandemic to the year prior using Wilcoxon signed rank test., Results: Of 53 patients who remained on chronic exchanges during the pandemic, use of depletion exchange increased (15%-23%) and FCR increased (34.9 [SD 4.7] vs. 37.6 [SD 4.5], p < .05). These changes resulted in 854 units conserved without clinically significant changes to pre-exchange laboratory parameters, including hemoglobin S%, or number of acute care presentations. In contrast, five patients who transitioned to predominantly simple transfusions, experienced difficulty maintaining hemoglobin S% less than 30 and worsening anemia., Discussion: Our data suggest that in a blood shortage crisis, optimizing the exchange procedure itself may be the safest means of conserving blood in a population of adult patients with sickle cell disease., (© 2022 AABB.)

Background: The United States (US) leads all high-income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients., Methods: Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all-payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson-regression models were used to estimate prevalence ratios (PR) of blood transfusion., Results: There were 168,315 ED visits and 58,815 hospitalizations (age = 18-90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18-24 years (31.8%), and assault-related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self-harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95%CI:4.15-5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10-2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission., Conclusions: Gun-related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs., (© 2021 AABB.)

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., (© 2021 AABB.)