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.

How do we achieve blinding in modern electronic and paper medical records during the conduct of transfusion trials?

BACKGROUND: Regulatory aspects of transfusion medicine add complexity in blinded transfusion trials when considering various electronic record keeping software and blood administration processes. The aim of this study is to explore strategies when blinding transfusion components and products in paper and electronic medical records. METHODS: Surveys were collected and interviews were conducted for 18 sites across various jurisdictions in North America to determine solutions applied in previous transfusion randomized control trials. RESULTS: Sixteen responses were collected of which 11 had previously participated in a transfusion randomized control trial. Various solutions were reported which were specific to the laboratory information system (LIS) and electronic medical record (EMR) combinations although solutions could be grouped into four categories which included the creation of a study product code in the LIS, preventing the transmission of data from the LIS to the EMR, utilizing specialized stickers and labels to conceal product containers and documents in the paper records, and modified bedside procedures and documentation. DISCUSSION: LIS and EMR combinations varied across sites, so it was not possible to determine combination-specific solutions. The study was able to highlight solutions that may be emphasized in future iterations of LIS and EMR software as well as procedural changes that may minimize the risk of unblinding.

Exploring Peaks in Hospital Blood Component Utilization: A 10-Year Retrospective Study at a Large Multisite Academic Centre.

Peak demand analysis is common in industries such as the energy sector, but can also be applied to the field of transfusion to characterize the nature and timing of peak days in hospital blood utilization. This information can be used to forecast future peak days or to inform hospital emergency preparedness plans. The aims of this study are to characterize peak days in red blood cell (RBC) utilization over the past 10 years at our hospital, and to compare RBC peaks with peaks in platelet, plasma, and cryoprecipitate utilization. This was a retrospective cohort study of RBC, platelet, plasma, and cryoprecipitate transfusions in the inpatient and emergency department setting between May 2009 and April 2019 at a large academic hospital, containing regional trauma and cardiovascular surgery centers. For each blood product, a peak in utilization was defined as a day with a ≥50% increase in the number of units transfused compared to the previous 90-day average. Descriptive and inferential analyses were performed to characterize peak days. There were on average 20,501 RBCs transfused per year and 56 RBCs transfused per day over the 10-year period. A total of 134 peaks in RBC utilization occurred over the study period, with an average of 14 peaks per year. RBC peak days required on average 69% more RBC units compared to nonpeak days (P< .0001). 77% of RBC peaks were caused either solely or in part by surgical bleeding, 34% were caused entirely or in part by trauma, and other causes were infrequent. RBC peaks occurred most often on Fridays and least often on weekends (P< .0001). While there were 134 RBC peaks over the study period, there was a larger number of platelet (n = 292), plasma (n = 467), and cryoprecipitate peaks (n = 579). RBC peak days often coincided with plasma peak days, but less frequently with platelet and cryoprecipitate peaks. More studies are needed to determine whether analysis of peak usage will be of value to hospital blood banks for emergency planning and blood inventory management.

Cold-Stored Platelets: Review of Studies in Humans.

Although numerous reviews and editorials have been published about the biologic features of platelets exposed to cold temperature and their in vitro function, none has focused on the data from studies after transfusion in healthy human participants and patients. This may, in part, be due to the paucity of well-controlled in vivo investigations of cold-stored platelets. Although numerous studies are looking into the recovery and survival of cold-stored platelets (ie, the percentage of infused platelets maintained in circulation over time), very few assess in vivo platelet function. Another caveat is that most studies were performed in the 1960s and 1970s, at a time when platelet collection and storage were different compared to today. Despite these limitations, we believe the transfusion community can take valuable information from these studies. This review is limited to data on cold-stored platelets in plasma or additive solution and does not include data on whole blood or resuspended whole blood from components because the hemostatic properties of whole blood are likely very different (the interested reader is referred to the review article focused on the hemostatic properties of platelets stored in whole blood by van der Meer et al in this special edition of Transfusion Medicine Reviews). In this review, we report that room temperature storage consistently results in a longer in vivo platelet circulation time at the expense of bacterial growth and shorter storage duration, resulting in expiration, wastage, and regional and national shortages. Cold storage of platelets universally results in moderately reduced recovery and markedly reduced survival. We found inconsistent data about the efficacy of cold-stored platelets likely due to study design differences. The analysis of the available data suggests that there is a short-lasting hemostatic effect of cold-stored platelets. Storage time or choice of anticoagulant did not have a clear effect on platelet efficacy after cold storage. In summary, more data and clinical trials are needed to better understand the effect of cold-stored platelets after transfusion into humans.

Volume-dependent effect of stored red blood cells: A secondary analysis of the Age of Blood Evaluation trial.

BACKGROUND: An increased risk of complications, including death, has been associated with stored red blood cell (RBC) units in observational studies but not in randomized trials. We aimed to evaluate for volume-dependent effects attributable to length of RBC storage in a secondary analysis of the Age of Blood Evaluation (ABLE) trial. STUDY DESIGN AND METHODS: In the 2510 critically ill adults from the ABLE trial randomized to receive RBC units stored not more than 7 days or the oldest compatible RBC units, we estimated the hazard ratio (HR) for death by intensive care unit (ICU) and hospital discharge and by days 28, 90, and 180, within subgroups defined by the number of RBC units received. Extended Cox proportional hazards regression was used to model the HR. RESULTS: A volume-dependent effect of storage age on survival was present for death by 90 and 180 days, but not earlier endpoints. The HR for death by 90 days was 0.55 (95% confidence interval [CI], 0.11-0.98, fresh vs standard) after transfusion of 6 RBC units but 1.45 (95% CI, 1.06-1.98) after transfusion of 1 RBC unit. CONCLUSION: In this exploratory analysis, volume-dependent effects related to RBC storage were documented in the ABLE trial. The harms associated with small volumes of fresh RBC units and large volumes of older RBC units should be further explored.

Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura.

Patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) often experience life-threatening relapses of the disease, and rituximab (RTX) can be used to mitigate relapse risk. However, the predictors of relapse in iTTP and the magnitude and duration of effect of RTX remain key unanswered questions. Using a multi-institutional cohort of consecutive adult patients with iTTP, we used survival analysis to compare relapse rates between patients who received RTX during the index presentation with acute iTTP and those who did not. Of 124 patients, 60 (48%) received RTX and 34 (27%) experienced relapse. Median time to relapse was 3.71 (interquartile range, 1.75-4.9) and 1.33 (interquartile range, 0.43-2.35) years for RTX-treated and untreated patients, respectively. RTX conferred protection from relapse at 1 year of follow-up (P = .01) but not at 5 years of follow-up. Extended Cox regression was then used to identify predictors of relapse and to estimate the protective effect of RTX. The following parameters were independently associated with increased risk for subsequent relapse: presenting in iTTP relapse (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.4-6.4), age younger than 25 years (HR, 2.94; 95% CI, 1.2-7.2), and non-O blood group (HR, 2.15; 95% CI, 1.06-4.39). RTX initially provided protection from relapse (HR, 0.16; 95% CI, 0.04-0.70), but this effect gradually diminished, returning to the baseline risk for untreated patients at approximately 2.6 years. Patients who are young, have non-O blood group, or present with relapsed iTTP are at increased risk for subsequent relapse. RTX appears to confer short-term protection from relapse.

Red blood cell alloantibodies are associated with increased alloimmunization against human leukocyte antigens.

BACKGROUND: Alloantibodies recognizing human leukocyte antigens (HLA) can cause immune-mediated refractoriness to platelet transfusion. An association between HLA alloimmunization and red blood cell (RBC) alloimmunization has been suggested but remains uncertain. STUDY DESIGN AND METHODS: We tested for HLA alloantibodies in 660 patients with and without RBC alloantibodies. Calculated panel reactive antibody (cPRA) values were determined for HLA alloimmunized patients. Current and historical diagnoses and blood product exposure were catalogued. Variables associated with high-level HLA alloimmunization (cPRA ≥ 90%) were evaluated. RESULTS: The cohort included 366 women and 294 men with median age of 66 years (interquartile range [IQR], 53-76). The number of patients with and without RBC alloantibodies was 447 and 213, respectively. Among patients with and without RBC alloantibodies, 20.6% and 8.5% had a cPRA ≥ 90%, respectively (p < 0.0001). In univariate analyses of men and nulliparous women and previously pregnant women, the median number of RBC alloantibodies was significantly higher in patients with a cPRA ≥ 90% (p < 0.0001). The number of RBC alloantibodies remained an independent predictor of a cPRA ≥ 90% in multivariate analysis (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.22-1.85). Other independent predictors of a cPRA ≥ 90% were parity (OR 1.26, 95% CI 1.08-1.47), age (OR 0.98, 95% CI 0.97-1.00), history of renal disease (OR 1.88, 95% CI 1.02-3.48), and number of non-leukoreduced products transfused (OR 1.02, 95% CI 1.00-1.04). CONCLUSIONS: RBC alloimmunization was significantly associated with HLA alloimmunization with a cPRA ≥ 90%. RBC alloimmunization status combined with specific components of the clinical history may estimate the risk of high-level HLA alloimmunization.

Perioperative management of a redo aortic root replacement in a patient with severe factor XI deficiency.

Factor XI deficiency is associated with significant bleeding in the setting of trauma and surgery. We present a patient with FXI deficiency and multiple red blood cell allo-antibodies requiring repeat aortic root replacement and discuss the perioperative management of patients with FXI deficiency undergoing cardiac surgery.

Synthesis, characterization, and computational study of MoSF4.

Molybdenum sulfide tetrafluoride was synthesized from MoF(6) and S(Si(CH(3))(3))(2) in CFCl(3) at low temperature and was fully characterized by Raman, infrared, and (19)F NMR spectroscopy and by X-ray crystallography. The crystal structure revealed that MoSF(4) forms infinite fluorine-bridged chains. Quantum-chemical calculations using B3LYP and PBE1PBE methods were used to calculate the gas-phase geometry and vibrational frequencies of monomeric MoSF(4) and (MoSF(4))(3)F(-). The vibrational frequencies of (MoSF(4))(3)F(-) have been used in the assignment of the vibrational spectra of solid MoSF(4). Natural bond order analyses were carried out for monomeric MoSF(4) and, for comparison, for WSF(4).

Synthesis, NMR and vibrational spectroscopic characterization, and computational study of the cis-IO2F3 2- anion.

The N(CH3)4(+) salt of the cis-IO2F3(2-) anion was synthesized from [N(CH 3)4][IO2F2] and excess [N(CH3)4][F] in CH3CN solvent. The [N(CH3)4] 2[IO2F3] salt was characterized by Raman, infrared, and (19)F solid-state MAS NMR spectroscopy. Geometry optimization and calculation of the vibrational frequencies at the DFT level of theory corroborated the experimental finding that the IO2F3(2-) anion exists as a single isomer with a cis-dioxo and mer-trifluoro arrangement. The fluorine atom in IO2F3(2-) that is trans to one of the oxygen atoms is weakly bound with a calculated bond length of 228.1 pm. The IO2F3(2-) anion is only the second example of an AEO 2F 3 species after XeO2F3(-).