Current state of undergraduate medical school training in transfusion medicine and its impact on postgraduate trainee knowledge.

BACKGROUND: Studies have described poor transfusion medicine (TM) knowledge in postgraduate trainees. The impact of undergraduate medical TM education on postgraduate knowledge is unclear. METHODS: Canadian medical schools were surveyed on the number of hours dedicated to TM teaching and topics covered by curricula during 2016-2020. Postgraduate trainees attending Transfusion Camp in 2021 completed a pretest of 20 multiple-choice questions. The survey results and pretest scores were compared to evaluate the association between undergraduate medical TM education and pretest scores. RESULTS: The survey was completed by 16 of 17 Canadian medical schools. The number of hours (h) of TM teaching were <2 h (25%), 3-4 h (25%), and >4 h (50%). Twelve of 19 Transfusion Camp topics were covered in ≥50% of schools. Eleven medical schools provided ethics approvals/waivers to include trainee pretest scores in the analysis (N = 200). The median pretest scores by medical school ranged from 48% to 70%. No association was found between number of TM teaching hours and average pretest scores (p = .60). There was an association between higher postgraduate year level and individual pretest score (p < .0001). The analysis by topic demonstrated questions where trainees from different schools performed uniformly well or poorly; other topics showed considerable variation. CONCLUSION: Variation in quantity and content of undergraduate TM teaching exists across Canadian medical schools. In this limited assessment, the number of TM teaching hours was not associated with performance on the pretest. This study raises the opportunity to re-evaluate the delivery (content, timing, consistency) of TM education in undergraduate medical schools.

The selection and preparation of red cell components for intrauterine transfusion: A national survey.

BACKGROUND AND OBJECTIVES: The practice regarding the selection and preparation of red blood cells (RBCs) for intrauterine transfusion (IUT) is variable reflecting historical practice and expert opinion rather than evidence-based recommendations. The aim of this survey was to assess Canadian hospital blood bank practice with respect to red cell IUT. MATERIALS AND METHODS: A survey was sent to nine hospital laboratories known to perform red cell IUT. Questions regarding component selection, processing, foetal pre-transfusion testing, transfusion administration, documentation and traceability were assessed. RESULTS: The median annual number of IUTs performed in Canada was 109 (interquartile range, 103-118). RBC selection criteria included allogeneic, Cytomegalovirus seronegative, irradiated, fresh units with most sites preferentially providing HbS negative, group O, RhD negative, Kell negative and units lacking the corresponding maternal antibody without extended matching to the maternal phenotype. Red cell processing varied with respect to target haematocrit, use of saline reconstitution (n = 4), use of an automated procedure for red cell concentration (n = 1) and incorporation of a wash step (n = 2). Foetal pre-transfusion testing uniformly included haemoglobin measurement, but additional serologic testing varied. A variety of strategies were used to link the IUT event to the neonate post-delivery, including the creation of a unique foetal blood bank identifier at three sites. CONCLUSION: This survey reviews current practice and highlights the need for standardized national guidelines regarding the selection and preparation of RBCs for IUT. This study has prompted a re-examination of priorities for RBC selection for IUT and highlighted strategies for transfusion traceability in this unique setting.

Comparison of automated solid phase versus manual saline indirect antiglobulin test methodology for non-ABO antibody titration: Implications for perinatal antibody monitoring.

BACKGROUND: Accurate antibody titration is crucial in prenatal evaluations to identify patients who need clinical monitoring for hemolytic disease of the fetus and newborn (HDFN) causing fetal anemia. This study compares the established gold standard method of manual tube saline indirect antiglobulin testing (SIAT) with the newer automated solid phase (ASP) method of antibody titration and aims to establish the critical titer threshold for ASP that corresponds to the previously established SIAT critical threshold of ≥16 used in our laboratory. STUDY DESIGN AND METHODS: One hundred fifty-seven prenatal and donor plasma samples with known antibodies were tested using both SIAT and ASP methodologies and results were compared. RESULTS: The study found that ASP titers were, on average, 1.33 dilutions higher than SIAT titers. The critical titer cutoff for ASP was determined to be ≥32, which is one tube higher than the SIAT cutoff of ≥16. DISCUSSION: The ASP method for antibody titration offers greater reproducibility and efficiency compared with manual SIAT titration. This study suggests that a titer cutoff of ≥32 is appropriate for most clinically significant antibodies using ASP. However, further research is needed to determine the comparability of ASP with SIAT in samples with multiple antibodies, anti-M antibodies, and other less common antibodies. Validation of the ASP titer cutoff against HDFN clinical outcomes is required before implementing this test for routine use in perinatal antibody titration.

Evaluating the inventory impact of utilizing low titer platelets in regional hospitals.

BACKGROUND: As a result of constrained supply, it is sometimes necessary to provide patients with ABO-mismatched platelets. Such practices increase the risk of acute hemolytic transfusion reaction (AHTR). Providing patients with platelets suspended in O plasma having low-titer Anti-A and Anti-B antibodies (LtABO) could reduce the incidence of AHTR. However, natural scarcity limits the number of such units that can be produced. In this paper we present a study to evaluate strategies for deploying LtABO at regional hospitals in Canada. STUDY DESIGN AND METHODS: Regional hospitals often experience demand for platelets on an irregular basis. They are, however, required to stock some number of platelets (typically one A-unit and one O-unit) for emergencies; outdates are common, with discard rates sometimes >>50%. A simulation study was completed to determine the impact of replacing a (1A, 1O) inventory with 2 or 3 units of LtABO at regional hospitals. RESULTS: A significant decreases in wastage and shortage can be expected by replacing a (1A, 1O) inventory policy with 2 units of LtABO. In tested cases, a 2-unit LtABO dominated a (1A, 1O) policy, resulting in statistically fewer outdates and instances of shortage. Holding 3 units of LtABO, increases product availability, but results in an increase in outdates when compared to a (1A, 1O) policy. CONCLUSION: Providing LtABO platelets to smaller, regional hospitals will lower wastage rates and improve patient access to care, when compared to existing (1A, 1O) inventory policies.

Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function.

Inflammasomes are caspase-1-activating multiprotein complexes. The mouse nucleotide-binding domain and leucine rich repeat pyrin containing 1b (NLRP1b) inflammasome was identified as the sensor of Bacillus anthracis lethal toxin (LT) in mouse macrophages from sensitive strains such as BALB/c. Upon exposure to LT, the NLRP1b inflammasome activates caspase-1 to produce mature IL-1ß and induce pyroptosis. Both processes are believed to depend on autoproteolysed caspase-1. In contrast to human NLRP1, mouse NLRP1b lacks an N-terminal pyrin domain (PYD), indicating that the assembly of the NLRP1b inflammasome does not require the adaptor apoptosis-associated speck-like protein containing a CARD (ASC). LT-induced NLRP1b inflammasome activation was shown to be impaired upon inhibition of potassium efflux, which is known to play a major role in NLRP3 inflammasome formation and ASC dimerization. We investigated whether NLRP3 and/or ASC were required for caspase-1 activation upon LT stimulation in the BALB/c background. The NLRP1b inflammasome activation was assessed in both macrophages and dendritic cells lacking either ASC or NLRP3. Upon LT treatment, the absence of NLRP3 did not alter the NLRP1b inflammasome activity. Surprisingly, the absence of ASC resulted in IL-1ß cleavage and pyroptosis, despite the absence of caspase-1 autoprocessing activity. By reconstituting caspase-1/caspase-11(-/-) cells with a noncleavable or catalytically inactive mutant version of caspase-1, we directly demonstrated that noncleavable caspase-1 is fully active in response to the NLRP1b activator LT, whereas it is nonfunctional in response to the NLRP3 activator nigericin. Taken together, these results establish variable requirements for caspase-1 cleavage depending on the pathogen and the responding NLR.