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* Context.--Ankylosing spondylitis (AS) is an autoimmune disorder with a strong genetic risk, especially with HLAB27. Clinical testing for HLA-B27 has been used to help diagnose patients with signs and symptoms of AS. Testing methods used by clinical laboratories for HLA-B27 fall into the broad categories of serologic/antibody- or molecular-based methods and have evolved over time. The College of American Pathologists (CAP) offers a proficiency testing survey for HLA-B27. Objective.--To analyze HLA-B27 testing trends and their performance in the past decade, using the proficiency testing survey data submitted to CAP. Design.--We analyzed the HLA-B27 CAP proficiency testing data from 2010 to 2020 for the method used, participant concordance, and error rates. Results from case scenarios to understand evolving scientific data around HLA-B27 risk alleles were also analyzed. Results.--Antibody-based flow cytometry is the most common method, though it has decreased from 60% in 2010 to 52% in 2020, with a corresponding increase in molecular methods. Among the molecular methods, real-time polymerase chain reaction has increased from 2% to 15%. Flow cytometry had the highest error rate (5.33%), and sequence-specific oligonucleotide (0%) is the most accurate (0%). Results of case scenarios demonstrated that most participants understood that allele-level HLA-B27 typing results inform clinical interpretation, for example HLA-B*27:06 is not associated with AS. Conclusions.--These data demonstrated the changing trends for HLA-B27 testing during the past decade. HLAB27 allelic typing provides a better understanding of AS association. This is possible by testing for the second field with methods like next-generation sequencing. (Arch Pathol Lab Med. 2024;148:149-154; doi: 10.5858/arpa.2022-0322-CP), Ankylosing spondylitis (AS) belongs to a group of autoimmune disorders termed spondylarthritis (SpA), which are chronic inflammatory disorders characterized by spinal and peripheral joint as well as extra-articular inflammation. There [...]

BackgroundAlthough 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 methodsNine 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.ResultsThe 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.ConclusionThe safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

Context.--Chimeric antigen receptor T-cell (CAR-T) technology has shown great promise in both clinical and preclinical models in mediating potent and specific antitumor activity. With the advent of US Food and Drug Administration-approved CAR-T therapies for B-cell lymphoblastic leukemia and B-cell non-Hodgkin lymphomas, CAR-T therapy is poised to become part of mainstream clinical practice. Objective.--To educate pathologists on CAR-T and chimeric antigen receptor-derived cellular therapy, provide a better understanding of their role in this process, explain important regulatory aspects of CAR-T therapy, and advocate for pathologist involvement in the delivery and monitoring of chimeric antigen receptor-based treatments. Much of the focus of this article addresses US Food and Drug Administration-approved therapies; however, more general issues and future perspectives are considered for therapies in development. Design.--A CAR-T workgroup, facilitated by the College of American Pathologists Personalized Health Care Committee and consisting of pathologists of various backgrounds, was convened to develop a summary guidance paper for the College of American Pathologists Council on Scientific Affairs. Results.--The workgroup identified gaps in pathologists' knowledge of CAR-T therapy, including uncertainty in the role of the clinical laboratory in supporting CAR-T therapy. The workgroup considered these issues and summarized the findings to assist pathologists to become stakeholders in CAR-T therapy administration. Conclusions.--This manuscript serves to both educate pathologists on CAR-T therapy and serve as a point of initial discussions in areas of CAR-T science, clinical therapy, and regulatory issues as CAR-T therapies continue to be introduced into clinical practice. (Arch Pathol Lab Med. 2021;145:704-716; doi: 10.5858/arpa.2019-0632-CP, Precision medicine for cancer therapy has used both targeted molecular approaches that are directed against a specific tumor-associated molecular aberration and immunomodulatory therapies, which enhance antitumor immunity. Immunomodulatory therapies either [...]

This document is a systematic review that discusses the challenges and inconsistencies in diagnosing cold agglutinins (CA), which are IgM autoantibodies that can cause hemolysis. The review aims to inform future research on the diagnostic investigation and interpretation of CA by describing serological techniques and cut-offs for diagnosing cold agglutinin disease (CAD) or cold agglutinin syndrome (CAS). The authors conducted a literature search and included 56 articles in their analysis, which revealed a lack of standardized definitions and thresholds for diagnosing clinically significant CA. The document provides a summary of various studies and case series related to cold agglutinins (CA), examining different aspects such as the number of participants with CA, the underlying clinical diseases studied, and the definition of CA. It presents a range of perspectives and findings from different studies. The article discusses the lack of consistency in defining the characteristics of cold agglutinin disease (CAD) in autoimmune hemolytic anemia (AIHA). The most commonly used laboratory test for diagnosing CAD is the direct antiglobulin test (DAT), which detects complement deposition on red blood cells. However, the clinical utility of DAT testing and the interpretation of results are variable. CA titers, which reflect the concentration and avidity of cold agglutinins, are also widely used but do not always correlate with disease severity. The determination of thermal amplitude [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

To the Editor.--Alloimmunization from fetomaternal hemorrhage remains an ongoing cause of hemolytic disease of the fetus and newborn. (1) Though failure rates of postnatal prophylaxis have decreased to less than [...]

The article discusses the historically low board pass rates in Blood Banking/Transfusion Medicine (BB/TM) and explores the possible causes. The authors suggest that the impact of the COVID-19 pandemic, including disruptions in education and training, may have contributed to the poor performance on the examination. They also mention the migration of trainee education from in-person settings to online learning during the pandemic and the need for further studies to evaluate the effectiveness of virtual learning. The authors conducted an investigation and found that the low pass rate in 2022 was not due to an issue with the standard setting process. However, they observed that the pass rate in 2021 was also lower than previous years, possibly reflecting the early phase of the pandemic's impact. The article concludes by noting that the BB/TM board pass rate in 2023 reached an all-time high, suggesting a return to normalcy in the post-COVID era. [Extracted from the article]

* Context.--Hemolytic transfusion reactions due to platelet transfusions containing ABO-incompatible plasma (ie, group O platelets into a non-group O patient) have been reported in the literature. However, limited data describe the extent to which transfusion services manage such platelet transfusions or the methods used to limit the risk of such reactions. Objective.--To determine transfusion services' current practices regarding the use of platelets containing ABO-incompatible plasma. Design.--In a College of American Pathologists' Transfusion Medicine Proficiency Testing Survey, supplemental questions asked participants whether a policy existed for the use of platelets containing ABO-incompatible plasma and, if a policy existed, what elements were part of the policy. Results.--Of 3156 laboratories that transfused platelets, 3152 responded to the question of whether they had a policy. Of these respondents, 83% (n = 2623) had a policy. One or more elements were reported for transfusions in adults: only ABO-compatible plasma products (n = 1363); only ABO-compatible plasma and platelet products (n = 679); notification of medical director (n = 646); notification of ordering physician (n = 637); volume limit of ABO-incompatible plasma allowed (n = 255); volume-reduction of ABO-incompatible products (n = 168); screening for critical titer of anti-A or anti-B (n = 53). A total of 529 laboratories indicated that they did not have a policy. Conclusions.--A majority of laboratories have a policy, but most do not include a method to limit the risk of hemolysis if platelets containing ABO-incompatible plasma must be transfused. When such platelets are used, there does not appear to be consensus on a specific method to minimize the transfusion of anti-A or anti-B. (Arch Pathol Lab Med. 2007;131:909-916), Platelet transfusions are indicated in patients with clinically significant bleeding attributable to thrombocytopenia or abnormal platelet function. Alternatively, prophylactic platelet transfusions may benefit severely thrombocytopenic patients in whom even small [...]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Fresh frozen plasma (FFP) is a frequently used human blood product to reverse the effects of vitamin K antagonists. While FFP is relatively economical, its large fluid volume can lead to hospitalization complications, therefore increasing the overall cost of use.Materials& Methods: A recently published article by Sarode et al., in Circulation, described the rate of volume overload associated with FFP use for reversal of vitamin K antagonists. This condition, described as transfusion-associated circulatory overload, has a defined rate of intensive care admission, which also has a well-reported average cost. The additional monetary value of intensive care unit admission and caring for fluid overload is then compared to the cost of another product, four-factor prothrombin complex concentrates, which does not, as per the Sarode paper, result in fluid overload.Results: The increased costs attributed to FFP-associated fluid overload for vitamin K antagonist reversal partly defrays the increased upfront cost of four-factor prothrombin complex concentrates.Discussion: FFP is commonly used to acutely reverse the effects of vitamin K antagonists. However, its use requires significant time for infusion, may lead to fluid overload, and is not fully effective in compete anticoagulation reversal. One alternative therapy for anticoagulant reversal is use of prothrombin complex concentrates, which are rapidly infused, are not associated with fluid overload, and are effective in complete reversal of coagulation measurements. This should be considered for patients with acute bleeding emergencies. [ABSTRACT FROM AUTHOR]