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.

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.

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.

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.

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.

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.

Platelet transfusion: a clinical practice guideline from the AABB.

BACKGROUND: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. METHODS: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).

Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage.

Importance: More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective: To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review: Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. Findings: It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Conclusions and Relevance: Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Using HLA typing to support patients with cancer.

BACKGROUND: The human leukocyte antigen (HLA) system plays a crucial role in immune function, and HLA testing is often needed in the support of patients with cancer. METHODS: We briefly review the published literature to clarify the nomenclature of the HLA system, currently available methods for HLA testing, and commonly used HLA assays. The uses of HLA testing in pharmacogenomics, disease association, platelet transfusion support, and in the management of both solid organ and hematopoietic stem cell transplantation are also reviewed. RESULTS: HLA testing is commonly performed for select patient populations, including patients with cancer and in those requiring solid organ and hematopoietic stem cell transplantation. CONCLUSION: Newer molecular typing methods have helped improve patient outcomes following hematopoietic stem cell transplantation.

Monthly haemostatic factor variability in women and men.

BACKGROUND: Hormonal status influences haemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1. DESIGN: We studied 103 subjects (39 premenopausal women, 18 postmenopausal women and 46 men) during three, randomized, 8-week energy- and nutrient-controlled experimental diets in the Dietary Effects on Lipids and Thrombogenic Activity (DELTA) Study. Fasting blood samples were collected weekly during the last 4 weeks of each diet period, and haemostatic factors were quantified. Two linear mixed-effects models were used for fibrinogen, factor VII and PAI-1: one to estimate and compare group-specific components of variance, and the other to estimate additional fixed effects representing cyclical functions of day of menstrual cycle in premenopausal women. RESULTS: Systematic cyclical variation with day of menstrual cycle was observed for fibrinogen (P < 0.0001), factor VII (P = 0.0012) and PAI-1 (P = 0.0024) in premenopausal women. However, the amplitude of cycling was small relative to the total magnitude of intra-individual variability. In addition, the intra-individual variance and corresponding coefficient of variation observed in premenopausal women did not differ from postmenopausal women and men. CONCLUSIONS: The variability in haemostatic factors in premenopausal women is no greater than for postmenopausal women or men. Consequently, premenopausal women can be included in studies investigating haemostatic factor responses without controlling for stage of menstrual cycle.

A Review of Laboratory Practices Using the HLA-B27 Survey by the College of American Pathologists: How Important Is Allele-Level Typing?

CONTEXT.­: Ankylosing spondylitis (AS) is an autoimmune disorder with a strong genetic risk, especially with HLA-B27. 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. HLA-B27 allelic typing provides a better understanding of AS association. This is possible by testing for the second field with methods like next-generation sequencing.

Red blood cell transfusion: a clinical practice guideline from the AABB*.

DESCRIPTION: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children. METHODS: These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

Defining and identifying laboratory literacy as a component of health literacy: An assessment of existing health literacy tools.

Health literacy has been defined and studied as an important component of a patient's ability to understand and obtain appropriate healthcare. However, a laboratory component of health literacy, as it pertains to the understanding of laboratory tests and their results, has not been previously defined. An analysis of readily available health literacy tools was conducted to determine laboratory testing-specific content representation. One hundred and four health literacy tools from a publicly available database were analyzed. Many of the health literacy tools were found to be lacking items related to laboratory testing. Of the health literacy tools that did contain a laboratory component, they were categorized pertaining to the laboratory test/testing content. Emerging from this process, eight competencies were identified that encompassed the entire range of laboratory-related aspects of health literacy. We propose that these eight competencies form the basis of a set of competencies needed for one to access, interpret, and act on laboratory results-a capacity we are referring to as "laboratory literacy."

Platelet-white blood cell (WBC) interaction, WBC apoptosis, and procoagulant activity in stored red blood cells.

BACKGROUND: Nonleukoreduced units of red blood cells (RBCs) contain activated platelets (PLTs) that interact with white blood cells (WBCs) and may promote inflammation and thrombosis in the recipient. The aim of this study was to characterize PLT-WBC interactions (PLT-WBC aggregates [PLAs]), WBC apoptosis, WBC death, and the development of procoagulant activity in RBCs during storage. STUDY DESIGN AND METHODS: RBCs were prepared from volunteer donor blood and stored. Samples were analyzed with flow cytometry between Days 1 and 15 to measure PLT-monocyte aggregate (PMA) and PLT-neutrophil aggregate (PNA) formation, WBC apoptosis (annexin V binding), and cell death (binding of 7-aminoactinomycin D). Procoagulant activity in the supernatant of four RBC preparations was assessed between Days 1 and 39 using a clotting assay with and without the addition of an inhibitory anti-tissue factor (TF) antibody, αTF-5. RESULTS: PLA formation was extensive and maximal on Day 3 of storage (PNA, 23 ± 13%; PMA, 93 ± 4%; n = 6). Apoptosis was progressive throughout storage, with 95 ± 4% of neutrophils and 73 ± 19% of monocytes binding annexin V on Day 15. Cell death became measurable after apoptosis. Procoagulant activity was observed in all RBCs but with varying temporal patterns. It was partially TF dependent and removed with high-speed centrifugation, suggestive of an association with microparticles. CONCLUSION: The activation of PLTs during the storage of RBCs induces PLA formation that precedes WBC apoptosis and death. Procoagulant activity, likely associated with microparticles derived from apoptotic WBCs, may contribute to adverse effects of stored, nonleukoreduced RBCs.

A Primer on Chimeric Antigen Receptor T-cell Therapy: What Does It Mean for Pathologists?

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.