Classification of posttransfusion adverse events using a publicly available artificial intelligence system.

BACKGROUND: Correct classification of transfusion reactions is important not only for effective patient care and donor management but also for accurate tracking of events in hemovigilance systems. We compared the ability of a generative artificial intelligence (AI) system to correctly diagnose hypothetical clinical situations as transfusion reactions in comparison to previous studies reporting the accuracy of transfusion medicine (TM) specialists in assessing these cases. METHODS: An AI system was requested to assess 36 case scenarios to provide a diagnosis, severity, and imputability of the transfusion reactions using the CDC National Healthcare Safety Network (NHSN) criteria. Responses were compared to an expert panel's classifications and to the published responses of a panel of TM specialists. Additionally, the AI's responses were compared to the TM specialists' prior attempts to use the TrDDx web-based algorithm for the five most challenging cases. RESULTS: The AI's classification accuracy varied widely depending on the NHSN category. The AI accurately classified all transfusion-associated circulatory overload and transfusion-related acute lung injury cases, exceeding TM specialists' assessments. Conversely, it did not correctly identify any cases in select NHSN categories such as DSTR. Overall accuracy among all diagnostic categories was 48.7% for AI responses versus 72.1% for prior TM specialist responses (p = 0.005). AI-generated responses included non-standard terminology, limited severity assessments, and no imputability determinations. DISCUSSION: A generative AI system may have a role in helping healthcare providers to consider transfusion reaction categories that might be missed, but caution is advised in applying the AI's output to transfusion reaction classification at present.

A global analysis of the use of immunoglobulin, shortages in supply, and mitigating measures: A survey of hospital providers (a BEST Collaborative study).

BACKGROUND: Immunoglobulin (IG) therapy is widely used to treat primary and secondary immune deficiencies and as immunomodulatory agent for various disorders. There is great concern that shortages of IG may rise, potentially affecting medical treatment options. STUDY DESIGN AND METHODS: An international survey was developed to study how intravenous immunoglobulins (IVIGs) are used and managed within hospitals in case of shortages. Study data were collected and managed using REDCap electronic data capture tools hosted by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. The survey was directed to hospital pharmacists and blood bank transfusion professionals and disseminated through members of the BEST Collaborative network. RESULTS: Survey respondents from institutions in the USA, Canada, Europe, Japan, and Australia (n = 13) confirmed that the primary specialties utilizing IG are neurology, hematology, and immunology. More than 60% of respondents reported IG supply shortages, but mitigation strategies were not well developed. DISCUSSION: As IG is the leading driver in plasma demand, more studies are needed to understand current and future demand for IG from the clinical perspective. Necessity lies in establishing clinical guidance to address shortages.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

Understanding barriers and facilitators of appropriate antibiotic use: a qualitative analysis of an online parenting forum.

PURPOSE: Antibiotic use and misuse are common in pregnant women and young children. Few studies have assessed real-world discussions of antibiotics in these populations. Using social media posts of pregnant women and parents, our goal was to identify key themes about facilitators and barriers to appropriate antibiotic usage. METHODS: A purposive sample of public posts and comments relevant to antibiotic use was collected from the BabyCenter United States social media site. Using a directed content analysis, themes related to facilitators and barriers to appropriate antibiotic use were identified. RESULTS: Seven hundred and twenty-six posts and 5227 comments were analysed. Themes centred around individual factors, interpersonal factors, and structural factors. Individual factors included knowledge and beliefs. Though misinformation was present, most parents were aware of appropriate antibiotic usage and perceived antibiotics as safe and effective. Some hesitance around using antibiotics led to recommendations for home remedies or over-the-counter treatments. Interpersonal factors focused on a lack of available offline peer support, the expertise of providers, as well as a potential lack of attention from those providers. Structural factors, including access to care, also impacted parents' antibiotic use and misuse. CONCLUSION: Though most parents demonstrated appropriate knowledge about antibiotics and a willingness to follow guidelines, negative experiences with their providers, a lack of support from peers, and structural factors presented as potential barriers to appropriate antibiotic use. Implementing avenues for peer support for parents, allowing more time for providers to address parents' concerns, and improving access to providers could improve appropriate antibiotic use in parents.

Incorporating the entity of under-transfusion into hemovigilance monitoring: Documenting cases due to lack of inventory.

BACKGROUND: Under-transfusion is an underreported entity within most hospitals and hemovigilance systems. While critical blood shortages are being reported more frequently, without incident codes to document instances of under-transfusion due to lack of inventory, estimating its impact on patient care as it relates to hemotherapy (HT) has hampered our ability to assess and inform strategic initiatives to combat inventory issues as well as prepare for future blood supply threats. STUDY DESIGN AND METHOD: An 11-member working group of the AABB (Association for the Advancement of Blood and Biotherapies) Hemovigilance Committee was formed in October 2020 to study the topic of under-transfusion including its potential causes and clinical expressions. The group was also charged with proposing simple definition/incident codes to be used by hemovigilance systems to document such instances. RESULTS: The working group proposed four simple incident codes under the new process code-No Blood (NB)-that can be used by hemovigilance systems to appropriately document instances of under-transfusion due to lack of inventory. The codes were described as: (1) NB 01-Inventory less than usual level due to supplier shortage; (2) NB 02-Demand for blood product exceeding usual inventory levels; (3) NB 03-Substitution with incompatible/inappropriate units; and (4) NB 04-Suboptimal dose/no transfusion given. CONCLUSION: The adoption of these codes within hemovigilance systems globally would assist in recognition and reporting instances of under-transfusion due to inventory, thus supporting development of better collection strategies, inventory management techniques as well as effective policies to improve blood safety and availability.

The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study.

BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

Pediatric resident knowledge of transfusion medicine: Results from the BEST-TEST3 international education needs assessment.

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.

Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese.

FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC-related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty-six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two-thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late-onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone-based or antisense oligonucleotide strategies for this particular type of myopathy.

A national survey of hospital-based transfusion services on their approaches to platelet bacterial risk mitigation in response to the FDA final guidance for industry.

BACKGROUND: Bacterial contamination of platelets is the leading infectious risk to the United States (US) blood supply. On 30 September 2019, the US Food and Drug Administration (FDA) published a Final Guidance for Industry to reduce the risk of transfusing platelets contaminated by bacteria. A national survey was undertaken to assess readiness, attitudes, and the potential impact on hospital-based transfusion services. STUDY DESIGN AND METHODS: A survey was distributed to transfusion services in all 50 US states. Summary statistics were performed along with review and categorization of email feedback and free text comments. RESULTS: Eighty-three transfusion services from 48 states participated in this survey study. Currently, the most common approach is primary culture performed at manufacturing (n = 49/83, 59%). Of the bacterial risk mitigation strategies provided by the FDA, the most frequently preferred are (a) pathogen reduced platelets (PRP) for up to 5-day storage (n = 36/77, 47%), (b) large volume delayed sampling (LVDS) ≥48 hours for up to 7-day storage (n = 16/77, 21%), and (c) primary culture ≥24 hours + secondary rapid testing for up to 7-day storage (n = 7/77, 9%). The main motivating factors for the survey participants' selected strategies to comply with FDA final guidance were product availability from supplier, reducing the risk of septic transfusion reactions (STR), and complexity of implementing and performing a new or additional test. CONCLUSION: While having platelets to transfuse and preventing STR are of the utmost importance, nationwide, the majority of transfusion services do not want to take on performing new or additional testing in their laboratories.

The effect of serum pretreatment regimens for the detection of HLA class I antibodies in platelet-refractory patients.

BACKGROUND: Single antigen bead (SAB) assays are used to identify human leukocyte antigen (HLA) antibodies in patients with platelet refractoriness due to HLA Class I alloimmunization. Some laboratories use serum pretreatment regimens to eliminate interference from immunoglobulin M antibodies and complement. These modifications may contribute to interlaboratory variability, which is a recognized problem with the SAB assay. STUDY DESIGN AND METHODS: Five patients' sera were overnight shipped to 12 laboratories in the United States and internationally. Recipients used their lab's SAB procedure to identify HLA Class I antibodies. The resultant mean fluorescence intensity (MFI) data were compared by instrumentation, bead lot, and pretreatment regimens. Laboratory-specific cutoffs for positive antibodies were applied to the results. RESULTS: Interlaboratory variability for MFI values appears to be associated with different pretreatment regimens. The coefficient of variation (CV) of MFI from samples pretreated with ethylenediaminetetraacetic acid, dithiothreitol, or heat inactivation (EDHI) were similar, ranging from 14% to 56% (mean, 22%). For samples with no pretreatment, the CVs were significantly higher than EDHI-treated samples, ranging from 25% to 74% (mean, 39%; 95% confidence interval, 12.10-21.90; p < 0.0001). An intralaboratory comparison of pretreatment regimens confirmed these findings. Some positive antibody specificities present in EDHI-treated samples were negative in corresponding samples with no pretreatment when laboratory-specific cutoffs for positive antibodies were applied. CONCLUSION: Our results show that greater interlaboratory precision can be achieved when samples are pretreated with EDHI as opposed to no pretreatment, likely because these pretreatments eliminate interference from inhibitors. Inhibitors may mask antibodies, leading to missed (or uncalled) specificities when no pretreatment is used.

Safety incident reports associated with blood transfusions.

BACKGROUND: Patient safety remains a critical issue in health care. Adverse events related to blood transfusion constitute a threat to patient safety. The aim of this study is to compare and contrast reporting trends of patient safety events that occur during the transfusion of blood components in pediatric and adult hospital care settings. STUDY DESIGN AND METHODS: This is a multicenter analysis of reported patient safety incidents occurring during the administration of blood components for four children's and 21 adult hospitals from January 2010 through September 2017. Denominators were pediatric or adult transfusions per year for a subset of two pediatric and two adult hospitals able to provide denominators for the complete reporting period. Rates were calculated on the subset of four hospitals per 100,000 components transfused with Pearson's chi square for comparison (p < 0.05 as significant). RESULTS: There were 1902 reports for an estimated 1.1 million transfusions: 358 reports from pediatric hospitals and 1544 reports from adult hospitals. From hospitals able to provide denominator data; there were 192 reports for 128,560 pediatric transfusions and 183 reports for 377,563 adult transfusions. The reporting rate per 100,000 components from these four hospitals was 149 for pediatric and 48 for adult reports (p < 0.01). CONCLUSION: This analysis demonstrates the continued need for transfusion safety practices. The type of incident reports differed in the pediatric setting compared to the adult setting. Understanding patient safety event reporting trends related to blood transfusion will help target hemovigilance education and interventions to the appropriate patient populations.

A consensus redefinition of transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion-related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life-threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI. STUDY DESIGN AND METHODS: An international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases. RESULTS: In the redefinition, the term "possible TRALI" has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies. CONCLUSIONS: Clinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion-associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.

Electronic patient identification for sample labeling reduces wrong blood in tube errors.

BACKGROUND: Wrong blood in tube (WBIT) errors are a preventable cause of ABO-mismatched RBC transfusions. Electronic patient identification systems (e.g., scanning a patient's wristband barcode before pretransfusion sample collection) are thought to reduce WBIT errors, but the effectiveness of these systems is unclear. STUDY DESIGN AND METHODS: Part 1: Using retrospective data, we compared pretransfusion sample WBIT rates at hospitals using manual patient identification (n = 16 sites; >1.6 million samples) with WBIT rates at hospitals using electronic patient identification for some or all sample collections (n = 4 sites; >0.5 million samples). Also, we compared WBIT rates after implementation of electronic patient identification with preimplementation WBIT rates. Causes and frequencies of WBIT errors were evaluated at each site. Part 2: Transfusion service laboratories (n = 18) prospectively typed mislabeled (rejected) samples (n = 2844) to determine WBIT rates among samples with minor labeling errors. RESULTS: Part 1: The overall unadjusted WBIT rate at sites using manual patient identification was 1:10,110 versus 1:35,806 for sites using electronic identification (p < 0.0001). Correcting for repeat samples and silent WBIT errors yielded overall adjusted WBIT rates of 1:3046 for sites using manual identification and 1:14,606 for sites using electronic identification (p < 0.0001), with wide variation among individual sites. Part 2: The unadjusted WBIT rate among mislabeled (rejected) samples was 1:71 (adjusted WBIT rate, 1:28). CONCLUSION: In this study, using electronic patient identification at the time of pretransfusion sample collection was associated with approximately fivefold fewer WBIT errors compared with using manual patient identification. WBIT rates were high among mislabeled (rejected) samples, confirming that rejecting samples with even minor labeling errors helps mitigate the risk of ABO-incompatible transfusions.

Analysis of pediatric adverse reactions to transfusions.

BACKGROUND: Children are known to be physiologically and biochemically different from adults. However, there are no multi-institutional studies examining the differences in the frequency, type, and severity of transfusion reactions in pediatric versus adult patients. This study aims to characterize differences between pediatric and adult patients regarding adverse responses to transfusions. STUDY DESIGN AND METHODS: This is a retrospective data analysis of nine children's hospitals and 35 adult hospitals from January 2009 through December 2015. Included were pediatric and adult patients who had a reported reaction to transfusion of any blood component. Rates are reported as per 100,000 transfusions for comparison between pediatric and adult patients. RESULTS: Pediatric patients had an overall higher reaction rate compared to adults: 538 versus 252 per 100,000 transfusions, notably higher for red blood cell (577 vs. 278 per 100,000; p < 0.001) and platelet (833 vs. 358 per 100,000; p < 0.001) transfusions. Statistically higher rates of allergic reactions, febrile nonhemolytic reactions, and acute hemolytic reactions were observed in pediatric patients. Adults had a higher rate of delayed serologic transfusion reactions, delayed hemolytic transfusion reactions, and transfusion-associated circulatory overload. CONCLUSION: Pediatric patients had double the rate of transfusion reactions compared to adults. The nationally reported data on reaction rates are consistent with this study's findings in adults but much lower than the observed rates for pediatric patients. Future studies are needed to address the differences in reaction rates, particularly in allergic and febrile reactions, and to further address blood transfusion practices in the pediatric patient population.

Obstetrics and gynecology physician knowledge of Rh immune globulin prophylaxis.

BACKGROUND: Previous studies have shown that more than 20% of laboratories would have recommended inaccurate doses of Rh immune globulin (RhIG) in hypothetical cases. Efforts have been made in educating laboratories in correct dosing calculations; however, obstetricians are most often responsible for ordering RhIG. The objective of this study was to assess knowledge of RhIG indications and dosing among obstetrics and gynecology (OB/GYN) physicians in the United States. STUDY DESIGN AND METHODS: An anonymous 17- question online survey was distributed to all OB/GYN resident and attending physicians affiliated with US residency training programs. RESULTS: A total of 165 surveys were collected, with 139 fully completed. Ninety-two percent of respondents correctly recognized the need for RhIG in D- patients with negative antibody screens. In a scenario of a fetomaternal hemorrhage (FMH) of 45 mL, only 22% of respondents correctly chose the appropriate RhIG dosage. Of those who were correct, 10% had correctly identified 30 mL as the amount of fetal whole blood covered by one dose of RhIG, while 48% incorrectly identified 15 mL (n = 31). A total of 49.3% of respondents reported residency as the most recent formal training on RhIG dosing and 35% reported never (n = 140). CONCLUSIONS: Our study found that OB/GYN physicians are knowledgeable regarding indications for RhIG immunoprophylaxis but were insufficient at calculating dosages in cases of FMH. More standardized education and training among OB/GYN physicians may decrease the risk of maternal alloimmunization, in part because RhIG dosage recommendations from laboratories are not standard practice.

An international survey on the role of the hospital transfusion committee.

BACKGROUND: Hospital transfusion committees (HTCs) can oversee all aspects of transfusion practice at a hospital. This survey sought to identify which quality variables were being reported at HTCs around the world. STUDY DESIGN AND METHODS: A working party composed of members of the Biomedical Excellence for Safer Transfusion (BEST) collaborative developed a survey of quality variables that could be potentially presented at HTC meetings. The survey was electronically sent to all BEST members who were encouraged to complete it if they were active on an HTC and to send it to other colleagues with similar experience. An expert panel was convened to determine which quality variables are the most important for review at HTC meetings. RESULTS: There were 121 respondents; the majority were from Europe (52%), Asia (19%), or North America (19%). Most respondents (68%) were at university hospitals. Of the 117 (97%) respondents with an HTC, the committee most often met quarterly (42%) and reviewed transfusion reactions (79%) and risk management-reported events (52%). The HTCs most commonly included transfusion medicine physicians, anesthesiologists, and other physicians who regularly transfuse blood products. Some of the most commonly reported quality variables included number of blood products transfused, wasted, and expired and the number of improperly labeled specimens. The expert panel analysis revealed that some variables that were deemed important were not being frequently reported at HTCs. CONCLUSION: There is variability in the variables being reported at HTCs around the world with some important variables not frequently reported.

Warm-reactive (immunoglobulin G) autoantibodies and laboratory testing best practices: review of the literature and survey of current practice.

BACKGROUND: Warm-reactive autoantibodies (WAAs) are the most common cause of autoimmune hemolytic anemia (AIHA) and can also be present without clinically significant hemolysis. WAAs complicate immunohematological testing, yet there is no commonly accepted approach to laboratory evaluation and red blood cell (RBC) selection. STUDY DESIGN AND METHODS: We searched PubMed/Cochrane Central for articles that described testing methodology and blood selection for patients with WAAs. We developed a 31-question survey regarding local practice for immunohematology testing and RBC selection in patients with WAAs (with or without AIHA). RESULTS: Eighty-six studies met the inclusion criteria and the aims of this review. Most of the literature was comprised of retrospective studies that often did not correlate laboratory results with clinical findings. Evidence-based protocols to guide testing and RBC selection for transfusion in patients with WAAs are lacking. Individuals representing 54 laboratories completed the survey. The responses indicated that numerous methodologies are used to identify underlying alloantibodies: 75% of respondents use autoadsorption; in patients who have a recent history of transfusion, 76% of respondents use alloadsorption; 58% of respondents perform direct antiglobulin testing (DAT) each time the indirect antiglobulin test is positive; and 48% perform eluate studies at the initial identification of WAAs. Responding laboratories may use phenotyping (98%) or genotyping (80%) at some point in the work-up. Seventy-five percent of respondents provide phenotype-matched or genotype-matched RBCs for transfusion. CONCLUSION: There is wide variability in immunohematology testing and RBC selection practices for patients who have WAAs (with or without AIHA). Future studies are needed to evaluate and compare the effectiveness of different testing algorithms and transfusion strategies.

Blood Group Antigen Matching Influence on Gestational Outcomes (AMIGO) study.

BACKGROUND: Red blood cell (RBC) antigen matching policies to prevent alloimmunization in females of childbearing potential (FCP) vary between centers. To inform transfusion centers responsible for making decisions about matching policies for FCPs, the causal stimulus of the antibodies implicated in severe hemolytic disease of the fetus and newborn (HDFN) must be determined. STUDY DESIGN AND METHODS: We conducted a multinational retrospective study of women with offspring affected by severe HDFN requiring neonatal exchange transfusion and/or intrauterine transfusion. Mothers treated at centers that provide extended antigen-negative RBCs (MATCH, five centers) and those that do not (NoMATCH, nine centers) were compared. RESULTS: A total of 293 mothers had at least one affected pregnancy: 179 at MATCH centers and 114 at NoMATCH centers. Most alloimmunization (83%) was attributed to previous pregnancy: 3% to transfusion (two cases at MATCH, six at NoMATCH centers) and 14% undetermined (both antecedent transfusion and pregnancy). Only 50 mothers had received transfusions; 13 had HDFN due to anti-K at MATCH and four at NoMATCH centers. Most (12/13, 92%) of the anti-K HDFN cases at MATCH centers had K+ paternal antigen status. Mothers at the MATCH centers do not appear to be protected from HDFN due to K, C, c, and E antibodies, although the low number of FCPs who received transfusions precluded drawing firm conclusions. CONCLUSION: The causal stimulus of antibodies that cause HDFN is predominantly from previous pregnancy. Although extended RBC matching for FCPs may impart some protection from allosensitization, we were unable to show a positive effect, possibly because matching policies are not uniform and there was a small number of mothers who previously received transfusions.

International validation of a dithiothreitol (DTT)-based method to resolve the daratumumab interference with blood compatibility testing.

BACKGROUND: Daratumumab (DARA) consistently interferes with routine blood bank serologic testing by directly binding to CD38 expressed on reagent red blood cells (RBCs). Treating RBCs with dithiothreitol (DTT) eliminates the DARA interference. We conducted an international, multicenter, blinded study aimed at validating the DTT method for use by blood bank laboratories worldwide. STUDY DESIGN AND METHODS: Paired plasma sample unknowns were sent to 25 participating blood bank laboratories. Sample 1 was spiked with DARA only (10 µg/mL), and Sample 2 with DARA plus a clinically significant RBC antibody (anti-D [n = 6], anti-Fya [n = 9], or anti-s [n = 10]). Sites were instructed to perform an antibody screen with and without DTT-treated RBCs and to use a DTT-treated RBC panel for antibody identification. Qualitative data about the DTT method were collected by online survey. The primary outcome was the proportion of study sites able to identify the antibody unknown in the presence of DARA. RESULTS: All sites observed the DARA interference with the antibody screen. The DARA interference was seen with all testing methods (gel, tube, or solid phase). Using the DTT method, 25 of 25 sites (100%) successfully identified the antibody unknown in the presence of DARA. Feedback on the DTT method was positive, with 17 of 19 (90%) sites responding to the survey indicating that they planned to use the DTT method to test clinical samples from DARA-treated patients. CONCLUSION: The DTT method is robust and reproducible and can be implemented by transfusion services worldwide to help provide safe blood products to patients treated with DARA.