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Introduction: Hospital-based transfusion involves hundreds of daily medical decisions. Medical decision-making under uncertainty is susceptible to cognitive biases which can lead to systematic errors of reasoning and suboptimal patient care. Here we review common cognitive biases that may be relevant for transfusion practice., Materials and Methods: Biases were selected based on categorical diversity, evidence from healthcare contexts, and relevance for transfusion medicine. For each bias, we provide background psychology literature, representative clinical examples, considerations for transfusion medicine, and strategies for mitigation., Results: We report seven cognitive biases relating to memory (availability heuristic, limited memory), interpretation (framing effects, anchoring bias), and incentives (search satisficing, sunk cost fallacy, feedback sanction)., Conclusion: Pitfalls of reasoning due to cognitive biases are prominent in medical decision making and relevant for hospital transfusion medicine. An awareness of these phenomena might stimulate further research, encourage corrective measures, and motivate nudge-based interventions to improve transfusion practice., (© 2024 The Author(s). Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

Background: It is uncertain how transfusion knowledge translates to practice. The purpose of the study was to determine if higher scores on a validated Transfusion Camp knowledge assessment test were associated with transfusion order appropriateness., Study Design and Methods: Eligible participants included postgraduate trainees and faculty physicians who had prescribed at least four transfusion orders in the preceding 6 months at two hospitals. Participant data and knowledge were collected using a web-based questionnaire with a validated Transfusion Camp knowledge assessment tool. The most recent 4-10 consecutive transfusion orders per prescriber were independently dually adjudicated for appropriateness based on published criteria. The primary outcome was the correlation between the score on six questions on red blood cells (RBCs), platelets (PLTs), and plasma from the validated test and the percentage order appropriateness. Generalized linear regression was conducted to determine if factors (sex, specialty, participation in Transfusion Camp, previous transfusion education, self-rated knowledge) were associated with appropriate orders., Results: Seventy-four participants (45 trainees, 29 faculty; 31 females, 43 males) completed the test. Median score was 66.7% (interquartile range [IQR]: 50.0, 83.3) for six questions on RBCs, PLTs, and plasma transfusions. Of 546 transfusion orders adjudicated, appropriateness was 90.7% (95% confidence interval [CI]: 87.9%-93.0%). The correlation between prescriber test scores and order appropriateness was very weak (r = -.08). In multivariable analysis, female prescribers (p = .02) and beginner (vs. intermediate) self-rated knowledge (p = .01) were associated with higher transfusion appropriateness., Conclusion: Transfusion knowledge test scores did not correlate with order appropriateness. Factors other than knowledge are key to understanding how to improve appropriate blood use., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Objectives: Anemia in pregnancy has negative impacts on maternal and neonatal morbidity and mortality and has been described as an issue of health equity. The primary aim of our study was to describe the rates of anemia near delivery and assess whether this correlates with neighbourhood-level income status., Methods: We conducted a retrospective cohort study of pregnant persons delivering from January 2012 through December 2022 at 2 large academic centres. We used log-binomial regression to estimate the association between neighbourhood-level income quintile and anemia near delivery, defined as a hemoglobin <110 g/L within 30 days of delivery, controlling for maternal age, parity, thalassemia trait, number of fetuses, blood group, and service provider type. Secondary maternal and fetal outcomes were analyzed descriptively., Results: A total of 51 782 deliveries were included; the majority were singleton (97%) pregnancies delivered vaginally (61%). Although 77% of patients had a complete blood count done within 30 days of delivery, only 13% had a ferritin value checked within 9 months of delivery. Approximately 30% of all patients were anemic near delivery, with higher rates of anemia in lower income quintiles; patients in the lowest income quintile were 18% more likely to be anemic than those in the highest income quintile (relative risk 1.18; 95% CI 1.12-1.25)., Conclusions: Even within a high-resource academic setting, anemia in pregnancy is common. Given the high rates of anemia in our study, particularly, amongst patients in lower income quintiles, widespread targeted educational and system interventions are required to ensure equitable patient care., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: The objective of this review is to compare the effectiveness and safety of larger versus smaller RBC volume per transfusion for anemia in hospitalized adults, children, and preterm neonates., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: To evaluate if implementation of the 2019 Society of Interventional Radiology (SIR) guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy is associated with increased haemorrhagic adverse events, change in pre-procedural blood product utilization, and evaluation of guideline compliance rate at a single academic institution. Methods: Ultrasound guided percutaneous liver biopsies from (January 2019-January 2023) were retrospectively reviewed (n = 504), comparing biopsies performed using the 2012 SIR pre-procedural coagulation guidelines (n = 266) to those after implementation of the 2019 SIR pre-procedural guidelines (n = 238). Demographic, preprocedural transfusion, laboratory, and clinical data were reviewed. Chart review was conducted to evaluate the incidence of major bleeding adverse events defined as those resulting in transfusion, embolization, surgery, or death. Results: Implementation of the 2019 SIR periprocedural guidelines resulted in reduced guideline non-compliance related to the administration of blood products, from 5.3% to 1.7% ( P = .01). The rate of pre-procedural transfusion remained the same pre and post guidelines at 0.8%. There was no statistically significant change in the incidence of bleeding adverse events, 0.8% pre guidelines versus 0.4% post ( P = 1.0). Conclusion: Implementation of the 2019 SIR guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy did not result in an increase in bleeding adverse events or pre-procedural transfusion rates. The guidelines can be safely implemented in clinical practice with no increase in major adverse events., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Author Alexandre Menard receives a speaker honorarium from Inari Medical and Philips Imaging and has received payment for expert testimony from the College of Physicians and Surgeons on Ontario. Author Jeannie Callum has received research grants from Canadian Blood Services and Octapharma and participates on a Drug Safety Monitoring Board for the FEISTY Trauma Trial. Author Emidio Tarulli receives consulting fees from the Medfall Group. The authors declare that they have no conflict of interest not listed above.

Background: This Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) provides an evidence-based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small-volume or conventional blood collection tubes?, Methods: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework., Results: We identified 8 studies (1 cluster and 2 patient-level randomized trials; 5 observational studies) comparing small-volume to conventional tubes. We had high certainty evidence that small-volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small-volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small-volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small-volume tubes on laboratory instrumentation., Conclusion: This ICM-RPG panel made a strong recommendation for the use of small-volume sample collection tubes in adult ICUs based on overall moderate certainty evidence., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background and Purpose: Anemia is common in locally advanced cervical cancer. Clinical practice varies greatly for management of anemia during brachytherapy, with some centres providing red cell transfusion to increase hemoglobin levels above 100 g/L., Materials and Methods: This is a retrospective observational cohort study of adult patients with cervical cancer treated with brachytherapy at two academic hospitals. One hospital (H1) uses a liberal transfusion strategy with hemoglobin threshold of 100 g/L during brachytherapy and the other uses a restrictive target of 70 g/L (H2)., Results: Overall, 336 patients met inclusion criteria (H1: 150 patients, H2: 186 patients). 11 patients were excluded (2 at H1, 9 at H2). Demographics at both sites were comparable, except for cancer stage and smoking history. External beam radiation and chemotherapy provided was similar. Hemoglobin values were compared at baseline (within 4 weeks of oncology consult), and prior to the first and second brachytherapy treatments. In total, 101red blood cell (RBC) units were transfused to patients at H1 and 19 units to patients at H2. Patients were followed for a median of 37.0 months (0.6-80.5) at H1, and 33.3 months (1.6-82.0) at H2. There was no significant difference in progression-free or overall survival. Multivariable logistic regression analysis showed that FIGO stage was a predictor for both overall survival and cancer progression. Age, tumor size, chemotherapy, and hemoglobin levels were not predictors of disease progression or mortality., Conclusions: The practice of liberal transfusion should be re-evaluated in the absence of robust data to support its use., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: In the prehospital tranexamic acid (TXA) for traumatic brain injury (TBI) trial, TXA administered within 2 hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT)., Methods: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial ( ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) ≤ 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors., Results: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was -8·5 percentage points (95% confidence interval [CI], -15.9 to -1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g infusion (estimated difference - 2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups., Conclusion: A 2-g out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing., Level of Evidence: Therapeutic/Care Management; Level II., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Massively bleeding trauma patients often arrive to intensive care units hypothermic. Active warming blankets have shown promise in reducing hypothermia in the pre-hospital setting, but less is known about their in-hospital use. The aim of this pilot evaluation was to understand the feasibility of the Ready-Heat ® blanket in a level 1 trauma centre to improve the management of hypothermia in massively bleeding trauma patients., Methods: This was a prospective, observational, feasibility study of 15 patients performed at a single level 1 trauma centre. Patients were eligible for enrollment if they presented to the trauma bay and a massive hemorrhage protocol was activated. Primary outcome measures (feasibility) included: blanket applied to the patient; temperature recording in the trauma bay, and next phase or final phase of care; and blanket remaining on patient upon arrival to the subsequent phase of care.Secondary outcome measures (safety) included skin irritation and cold discomfort. Use of the Ready-Heat ® blanket was considered feasible if 10 of 15 patients met all four criteria for feasibility., Results: The Ready-Heat ® blanket was placed on all patients with mean time to blanket application of 24 (± 13.4) minutes. Thirteen patients (86.7%) met all four criteria for feasibility. Initial challenges were identified in the first five patients including proper blanket application, keeping the blanket on the patient through subsequent phases of care, and failure to obtain temperature recordings., Conclusion: The Ready-Heat ® blanket proves feasible for this patient population. A larger study focusing on hypothermia prevention and treatment is warranted., Trial Registration Number: NCT04399902., Date of Registration: May 22, 2020., Competing Interests: Declarations. Conflict of interest: None declared. Meetings where work was presented: Poster presentation, Trauma Association of Canada Conference, 2020., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy-safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed., Methods and Analysis: LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is 'effective' if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or 'ineffective' if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety., Ethics and Dissemination: The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients., Trial Registration Number: NCT05523297., Competing Interests: Competing interests: KK has received research funding or honoraria from Octapharma, Werfen, and Genentech. JB has received research funding or honoraria from Octapharma, Grifols, and Canadian Blood Services. JC has received research funding or honoraria from Octapharma and Canadian Blood Services. CS and SK are employees of Octapharma. JL serves on Advisory or Steering Committees for Bayer, Grifols, Octapharma, Takeda, and Werfen., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis., Study Design and Methods: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation., Results: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused., Interpretation: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. C. receives research support from Canadian Blood Services and Octapharma and serves on the board of directors of the Canadian Hematology Society. N. J. S. is a director of the National Board of Echocardiography and receives royalties from Wolters Kluwer. A. B. is an employee of Canadian Blood Services. H. K. is an employee of Canadian Blood Services. E. G. C. receives research funding (related to albumin) from Department of Medicine, The Ottawa Hospital and University of Ottawa, The Ottawa Hospital Academic Medical Organization, Kidney Foundation of Canada, and Physician Services Incorporated Foundation; is an editorial board member of the Canadian Journal of Kidney Health and Disease; and is a member of the Contrast-Associated Acute Kidney Injury guideline panel for the Canadian Association of Radiologists. B. R. is a guideline methodologist for American Thoracic Society, the Society of Critical Care Medicine, and Canadian Blood Services; is the Knowledge Translation director for Canadian Critical Care Society; is the grants and manuscripts chair for Canadian Critical Care Trials Group, and in a guideline group member for multiple guidelines. S. R. B. is the chair of the Clinical Pharmacy and Pharmacology section for the Society of Critical Care Medicine (not albumin use related), is a paid consultant for Wolters Kluwer (Lexicomp), is a Society of Critical Care Medicine Social Media Committee member, is a Surviving Sepsis Campaign Research Committee member, and has received a research grant from the National Institute of General Medicine Sciences. L. C. is a guideline group member for the British Society of Gastroenterology (management of ascites in liver cirrhosis), is involved in peer-reviewed publications (multiple topics including relevant to albumin use), received lecturer honoraria for the Canadian Liver Conference 2022, is a hepatology consultant for the Royal Free Hospital London, and is a Liver Committee member of the British Society of Gastroenterology. M. F. receives consultant fees from Cerus Corporation and Biocogniv, Inc.; has received honoraria from Grifols (none were albumin related); is a board member for Project Santa Fe Foundation and the American Board of Pathology; is the Histocompatibility and Identity Testing Committee Chair for College of American Pathologists; is co-team leader for the Biomedical Excellence for Safer Transfusion (BEST)Collaborative; and is the Editorial Committee co-chair for the ICTMG. R. J. has received fellowship funding from Canadian Blood Services, is an employee of William Osler Health System and the University of Cincinnati Medical Center, and is a panel member for ICTMG Platelet Utilization guideline development group. K. P. serves on the board of directors in North America for International Society for Blood Transfusion (ISBT), is a 2023 Association for the Advancement of Blood and Biotherapies (AABB) Red Blood Cells (RBC) guideline panel member, and is a member of the National Advisory Committee of Blood and Blood Products. P. S. S. is director of the Canadian Neonatal Network, director of the Canadian Preterm Birth Network, director of the International Network to Evaluate Outcomes of Neonates, and an external advisory board member for the Canadian Perinatal Surveillance system (none related to albumin manufacturers). H. S. is a consultant for Terumo and Cerus (not albumin related). Z. M. S. is a consultant and advisory board member of Grifols, Fresenius Kabi, and Novartis; receives research funding from Erydel and Fresenius Kabi; serves on the board of directors for the BEST Collaborative and International Council for Commonality in Blood Banking Automation (ICCBBA), Inc.; is the AABB Committee Chair; is vice chair, treasurer, and committee chair for ICCBBA, Inc.; is treasurer for BEST Collaborative; and has a family member (child) who is a summer intern with Grifols, Inc. T. T. is a paid consultant for Inter-View Partners France, A+A, Bayer HealthCare SAS, BVA, Axess Research, and All Global; has received honoraria from AbbeVie, Gilead Sciences, Advanz Pharma France, and Ipsen Pharma; in the principal investigator of randomized controlled trial Albumin Administration in Cirrhotic Patients With Bacterial Infection and a Systemic Inflammatory Response Syndrome Unrelated to Spontaneous Bacterial Peritonitis (ALB-CIRINF) (ClinicalTrials.gov Identifier, NCT01359813) published in 2015; and is a member of the Liver Cirrhosis-related Complications (LCC)-International Special Interest Group. B. W. is a resident physician at Loma Linda University Medical Center. S. S. is chair of the ICTMG and is an employee of National Health Service Blood and Transplant (NHSBT), a blood service operator in England. However, NHSBT is not a manufacturer of the intervention. N. S. is an employee of Canadian Blood Services; receives research funding from the Canadian Institutes for Health Research (Transfusion Requirements in Younger Patients Undergoing Cardiac Surgery [TRICS-IV] RBC transfusion in young cardiac patients; not related to albumin); is an advisory board member for Fresenius Kabius and Janssen; has received honoraria from the International Financial Corporation of the World Bank, Canadian Blood Services, and Ferring; and serves on the PKD guideline panel and ICTMG guideline panels (Fetal Neonatal Alloimmune Thrombocytopenia [FNAIT], Hemolytic Disease of the Newborn [HDN], platelet transfusion, RBC specifications). None declared (D. F., S. A., M. N., C. P., S. R.). See Appendix 8 for the ICTMG Conflict of Interest Policy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Prothrombin time (PT) and its derivative international normalized ratio (INR) are frequently ordered to assess the coagulation system. Plasma transfusion to treat incidentally abnormal PT/INR is a common practice with low biological plausibility and without credible evidence, yet INR targets appear in major clinical guidelines and account for the majority of plasma use at many institutions. In this article, we review the historical origins of INR targets. We recount historical milestones in the development of the PT, discovery of vitamin K antagonists (VKAs), motivation for INR standardization, and justification for INR targets in patients receiving VKA therapy. Next, we summarize evidence for INR testing to assess bleeding risk in patients not on VKA therapy and plasma transfusion for treating mildly abnormal INR to prevent bleeding in these patients. We conclude with a discussion of the parallels in misunderstanding of historic PT and present-day INR testing with lessons from the past that might help rationalize plasma transfusion in the future., Competing Interests: Declaration of competing interests The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the clinical details; and preparation, review, or approval of the manuscript. One of the authors (R.S.) paid expert testimony for 1 case in 2023 to do with an international normalized ratio of 1.7 that was not corrected. All other authors have no financial or personal relationships or affiliations that could influence the decisions and work on this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Iron-deficiency anaemia, occurring in 30-40% of patients undergoing cardiac surgery, is an independent risk factor for adverse outcomes. Our long-term goal is to assess if postoperative i.v. iron therapy improves clinical outcomes in patients with preoperative iron-deficiency anaemia undergoing cardiac surgery. Before conducting a definitive RCT, we first propose a multicentre pilot trial to establish the feasibility of the definitive trial., Methods: This internal pilot, double-blinded, RCT will include three centres. Sixty adults with preoperative iron-deficiency anaemia undergoing non-emergency cardiac surgery will be randomised on postoperative day 2 or 3 to receive either blinded i.v. iron (1000 mg ferric derisomaltose) or placebo. Six weeks after surgery, patients who remain iron deficient will receive a second blinded dose of i.v. iron according to their assigned treatment arm. Patients will be followed for 12 months. Clinical practice will not be otherwise modified. For the pilot study, feasibility will be assessed through rates of enrolment, protocol deviations, and loss to follow up. For the definitive study, the primary outcome will be the number of days alive and out of hospital at 90 days after surgery., Ethics and Dissemination: The trial has been approved by the University Health Network Research Ethics Board (REB # 22-5685; approved by Clinical Trials Ontario funding on 22 December 2023) and will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practices guidelines, and regulatory requirements., Clinical Trial Registration: NCT06287619., Competing Interests: JB is supported in part by a merit award from the 10.13039/100031443Department of Anesthesiology and Pain Medicine, 10.13039/501100003579University of Toronto, and has received funding or honoraria from Octapharma, Grifols, and Canadian Blood Services. KK is supported in part by a merit award from the 10.13039/100031443Department of Anesthesiology and Pain Medicine, 10.13039/501100003579University of Toronto, and has received research support, honoraria, or consultancy for speaking engagements from Octapharma, 10.13039/100006353Instrumentation Laboratory, and 10.13039/100004326Bayer. JC has received research support from 10.13039/501100000014Canadian Blood Services and Octapharma. YL has received research support from 10.13039/501100000014Canadian Blood Services and Octapharma, and is a consultant with Choosing Wisely Canada., (© 2024 The Authors.)

Background: Hospital transfusion services order blood products to satisfy orders and maintain inventory levels during unexpected periods of increased blood demand. Surplus inventory may outdate before being allocated to a recipient. Blood product outdating is the largest contributor to blood wastage., Study Design: A province-wide redistribution program was designed and implemented to redistribute near-outdate plasma protein and related blood products from low-usage to high-usage hospitals. Program operations and details are described in this paper. Two transport container configurations were designed and validated for transport of all blood products. A cost-analysis was performed to determine the effectiveness of this redistribution program., Results: A total of 130 hospital transfusion services contributed at least one near-outdate blood product for redistribution between January 2012 and March 2020. These services redistributed 15,499 products through 3412 shipments, preventing the outdating of $17,570,700 CAD worth of product. Program costs were $14,900 for shipping and $30,000 for staffing. Failed time limits or non-compliance with packing configurations resulted in $388,200 worth of blood products (97 shipments containing 816 products) being discarded. Courier transport delays was the most common reason (42/97; 43%) for transport failure., Conclusion: Redistributing near-outdate blood products between hospitals is a feasible solution to minimize outdating. Despite heterogeneity of Canadian blood product inventory, all products (each with unique storage and transport requirements) were successfully redistributed in one of two validated and simple containers. Total operation costs of this program were small in comparison to the $17.6 million in savings associated with preventing the discard of outdated products., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Race and ethnicity are sociopolitical and not biological constructs, and assertions that these population descriptors have scientific meaning has caused significant harm. A critical assessment of the transfusion medicine literature is an important aspect of promoting race-conscious as opposed to race-based medicine. Utilizing current definitions and health equity frameworks, this review will provide a critical appraisal of transfusion medicine studies at the intersection of race and healthcare disparities, with a focus on larger methodological challenges facing the transfusion medicine community. Moving forward, risk modelling accounting for upstream factors, patient input, as well as an expert consensus on how to critically conduct and evaluate this type of literature are needed. Further, when using race and ethnicity in research contexts, investigators must be aware of existing guidelines for such reporting., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Platelets stored at 1-6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20-24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP., Methods: This protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product)., Discussion: DCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study., Trial Registration: NCT06147531 (clinicaltrials.gov)., (© 2024. The Author(s).)

Background: End of life care for Children and Young People (CYP) is known to be an emotive area of practice. Previous studies involving qualified nurses have demonstrated that nurses feel they need more end-of-life care education, as well as a platform for sharing experiences and discussing them with others. Evidence relating to nursing students remains limited despite being widely acknowledged as a difficult aspect of nursing education., Aims: This study aims to help improve understanding of the lived experiences of children's nursing students who have cared for a patient at, during, or immediately following end-of-life. The study describes the emotions experienced by children's nursing students and explores the student nurses' perceptions of education and support needs around caring for CYP during end-of-life care., Methodology: A qualitative inquiry methodology allowed for a pragmatic approach to design this focus group study. Nine undergraduate student children's nurses participated in two focus groups. Ethical approval was granted by the host university. Thematic data analysis using Braun and Clarke's (2019) thematic analysis was conducted., Findings: Six themes emerged from the data; Emotional practice (1), the heart of the care (2), a lasting impact (3), hierarchy of grief (4), experience, knowledge and understanding (5), and the value of support (6). End of life care for children and young people is recognised by students as a sad but important part of the job role, which can have a lasting impact and which students required improved education and support for., Implications for Practice: Improved education on end-of-life care is required. This should be introduced early, encompassing practical approaches to the varied nature of end-of-life care, normalising a range of emotions and delayed responses. Furthermore, improved support is required for both student nurses and qualified staff, who are supporting students caring for CYP at the end of life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence-based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes., Study Design and Methods: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581)., Results: In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty-seven outcomes were reported with a mean of 11 (min-max. 4-32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage., Conclusion: There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence., Aim: To reduce unnecessary transfusion of albumin., Interventions: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage., Implementation and Evaluation: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures., Results: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period., Conclusion: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin., Competing Interests: Competing interests: JC has received research support from Canadian Blood Services and Octapharma. SAS has received honorarium from AstraZeneca, Novo Nordisk, Otsuka and KVR Pharmaceuticals. GD has received research funding from MaRS/Merck & Co and from Pfizer, as well as a honorarium from Merck & Co for a speaking engagement and from AstraZeneca for participation in a working group., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings., Methods: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population., Results: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078., Discussion: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

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., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Purpose: Anemia reduces the blood's ability to carry and deliver oxygen. Following cardiac surgery, anemia is very common and affects up to 90% of patients. Nevertheless, there is a paucity of data examining the prognostic value of postoperative anemia. In this narrative review, we present findings from the relevant literature on postoperative anemia in cardiac surgery patients, focusing on the incidence, risk factors, and prognostic value of postoperative anemia. We also explore the potential utility of postoperative anemia as a therapeutic target to improve clinical outcomes., Source: We conducted a targeted search of MEDLINE, Embase, and the Cochrane Database of Systematic Reviews up to September 2022, using a combination of search terms including postoperative (post-operative), perioperative (peri-operative), anemia (anaemia), and cardiac surgery., Principal Findings: The reported incidence of postoperative anemia varied from 29% to 94% across the studies, likely because of variations in patient inclusion criteria and classification of postoperative anemia. Nonetheless, the weight of the evidence suggests that postoperative anemia is common and is an independent risk factor for adverse postoperative outcomes such as acute kidney injury, stroke, mortality, and functional outcomes., Conclusions: In cardiac surgery patients, postoperative anemia is a common and prognostically important risk factor for postoperative morbidity and mortality. Nevertheless, there is a lack of data on whether active management of postoperative anemia is feasible or effective in improving patient outcomes., (© 2023. Canadian Anesthesiologists' Society.)

Introduction: Iron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of life, and decreases symptoms among patients with HF with reduced ejection fraction (HFrEF) and iron deficiency. Despite this, many patients are not screened or treated for IDA. We aimed to increase rates of screening and treatment of IDA among HF patients through the introduction of curated materials to aid HF clinicians with appropriate screening and treatment., Methods: We conducted a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at two ambulatory cardiology clinics in Toronto, Ontario. A quality improvement initiative was then introduced, which consisted of education and curated materials to aid clinicians in the screening and treatment of IDA among HFrEF patients. The proportion of patients screened and treated for IDA preintervention and postintervention were compared using χ 2 tests of Independence., Results: In the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA. Among those screened, 64.4% (n=29) had IDA. Only 17.2% (n=5) of these were treated with IV iron. After implementation of the quality improvement initiative, 90.9% (n=60) of patients with anaemia were screened for IDA (p<0.001) and 90.3% (n=28) of those with IDA were treated with IV iron (p<0.001)., Conclusion: The introduction of curated materials to aid clinicians was associated with increased rates of screening and treatment of IDA among ambulatory HFrEF patients. Further work is required to identify barriers and implement strategies to increase screening and treatment rates of IDA among HFrEF patients., Competing Interests: Competing interests: YL and JC have received research funding from Octapharma and the Canadian Blood Services. SP has received research funding from Boehringer-Ingelheim and has participated in a clinical trial with Abbott within the past two years. SP is a member of a speakers’ bureau for Agence L.I.V., University of Toronto, and University Health Network. YL has acted as a consultant for Choosing Wisely Canada. SP is a member of a national heart failure advisory board that works with AstraZeneca, Boehringer-Ingelheim, Novartis, and Servier., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The optimal hemoglobin (Hb) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined., Study Design and Methods: We conducted a pilot randomized multi-center study of two transfusion algorithms (liberal, to maintain Hb 110-120 g/L, transfuse 2 units if Hb < 105 g/L and 1 unit if Hb 105-110 g/L vs. restrictive, 85-105 g/L, transfuse 2 units when Hgb < 85 g/L). Primary objectives were 70% compliance in maintaining the q2 week hemoglobin within the targeted range and the achievement of a 15 g/L difference in pre-transfusion Hb. Secondary outcomes included measures of quality of life (QOL), iron studies and safety., Results: Twenty-eight patients were randomized between February 2015-2020, 13 to the restrictive arm and 15 to the liberal arm in three tertiary care centers. The compliance was 66% and 45% and the mean pre-transfusion Hb thresholds were 86 (standard deviation [SD] 8) and 98 g/L (SD 10) in the restrictive and liberal arms, (mean difference 11.8 g/L, p < .0001), respectively. Patients in the liberal arm experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) more units of blood during the 12-week study. Ferritin increased by 1043 (SD 1516) IU/L and 148 (SD 1319) IU/L in the liberal and restrictive arms, respectively. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important improvements in the liberal arm compared with the restrictive arm for selected symptoms and function domains., Conclusion: The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients., (© 2024 AABB.)

Background: Intravenous albumin is commonly utilised in cardiovascular surgery for priming of the cardiopulmonary bypass circuit, volume replacement, or both, although the evidence to support this practice is uncertain. The aim was to compare i.v. albumin with synthetic colloids and crystalloids for paediatric and adult patients undergoing cardiovascular surgery for all-cause mortality and other perioperative outcomes., Methods: A systematic review and meta-analysis of randomised controlled trials (RCTs) of i.v. albumin compared with synthetic colloids and crystalloids on the primary outcome of all-cause mortality was conducted. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use; subgroups were analysed by age, comparator fluid, and intended use (priming, volume, or both). We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CCRT) from 1946 to November 23, 2022., Results: Of 42 RCTs, mortality was assessed in 15 trials (2711 cardiac surgery patients) and the risk difference was 0.00, 95% confidence interval (CI) -0.01 to 0.01, I 2 =0%. Among secondary outcomes, i.v. albumin resulted in smaller fluid balance, mean difference -0.55 L, 95% CI -1.06 to -0.4, I 2 =90% (nine studies, 1975 patients) and higher albumin concentrations, mean difference 7.77 g L -1 , 95% CI 3.73-11.8, I 2 =95% (six studies, 325 patients)., Conclusions: Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids. The lack of improvement in important outcomes with albumin and its higher cost suggests it should be used restrictively., Systematic Review Protocol: PROSPERO; CRD42020171876., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: There is a literature gap in terms of albumin utilization practices., Methods/materials: We conducted a single-center retrospective observational electronic audit of adult admitted patients who received one or more vials of albumin (5% or 25%) between September 1, 2019 and August 31, 2020 at a large community hospital. The Research Ethics Board approval was obtained. Utilization data identified through the laboratory information system were independently adjudicated by two reviewers and resolved by consensus as appropriate-acceptable, appropriate-may be acceptable, or inappropriate. The primary objective of this audit is to determine the proportion of 5% and 25% intravenous albumin infusions meeting a priori appropriateness criteria for indication. Secondary outcomes include determining the patterns of practice surrounding intravenous albumin use: patient demographics, most responsible diagnosis, location at time of order, clinical outcomes of albumin recipients, and types, volumes, and cost of albumin infused., Results: The mean total albumin administered was 569.2 mL across 456 total recipients (58% male) with a 29% appropriateness rate. This cohort had an in-hospital mortality rate of 38%, with an average of 6 days from first dose of albumin to death. The mean length of stay was 14 days, with a mean intensive care length of stay of 8 days. The purchase cost of inappropriately transfused albumin was CAD $65,538., Conclusion: Based on a lack of or an unacceptable indication provided, 71% of patients were inappropriately transfused. Albumin use deviating from guideline recommendations may be contributing to increased healthcare costs, pressure on limited supply, and potential patient harm., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Managing Canada's immunoglobulin (Ig) product resource allocation is challenging due to increasing demand, high expenditure, and global shortages. Detection of groups with high utilization rates can help with resource planning for Ig products. This study aims to uncover utilization subgroups among the Ig recipients using electronic health records (EHRs)., Methods: The study included all Ig recipients (intravenous or subcutaneous) in Calgary from 2014 to 2020, and their EHR data, including blood inventory, recipient demographics, and laboratory test results, were analyzed. Patient clusters were derived based on patient characteristics and laboratory test data using K-means clustering. Clusters were interpreted using descriptive analyses and visualization techniques., Results: Among 4112 recipients, six clusters were identified. Clusters 1 and 2 comprised 408 (9.9%) and 1272 (30.9%) patients, respectively, contributing to 62.2% and 27.1% of total Ig utilization. Cluster 3 included 1253 (30.5%) patients, with 86.4% of infusions administered in an inpatient setting. Cluster 4, comprising 1034 (25.1%) patients, had a median age of 4 years, while clusters 2-6 were adults with median ages of 46-60. Cluster 5 had 62 (1.5%) patients, with 77.3% infusions occurring in emergency departments. Cluster 6 contained 83 (2.0%) patients receiving subcutaneous Ig treatments., Conclusion: The results identified data-driven segmentations of patients with high Ig utilization rates and patients with high risk for short-term inpatient use. Our report is the first on EHR data-driven clustering of Ig utilization patterns. The findings hold the potential to inform demand forecasting and resource allocation decisions during shortages of Ig products., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Severe traumatic bleeding depletes coagulation factor XIII (FXIII) and fibrinogen. However, the role of FXIII level in bleeding-related outcomes is unknown., Objectives: To evaluate the association between FXIII levels at hospital arrival and critical administration threshold (≥3 red blood cell units in 1 hour within the first 24 hours), bleeding-related outcomes, death, and baseline characteristics., Methods: A retrospective cohort study was conducted in severely injured adult patients (Injury Severity Score of ≥22 or ≥2 red blood cell units transfused in 24 hours) admitted to a level 1 trauma center. Clinical and laboratory data were collected. Baseline FXIII antigen levels were measured in banked patient plasma. Multivariable logistic and linear regression models were used to estimate the association between FXIII levels, outcomes, and baseline characteristics., Results: Three hundred sixty-four of 1730 subjects admitted during a 2-year period were analyzed. Median age was 44 years (IQR, 27-62 years), and median Injury Severity Score was 29 (IQR, 22-34). FXIII levels were not associated with critical administration threshold (odds ratio [OR], 1.06; 95% CI, 0.97-1.17) or death (OR, 0.98; 95% CI, 0.90-1.07). FXIII was associated with major bleeding (OR, 1.10; 95% CI, 1.02-1.2) and massive transfusion (OR, 1.25; 95% CI, 1.08-1.44). Lower baseline FXIII levels were associated with arrival from a referring hospital (FXIII level, -0.07 U/mL; 95% CI, -0.11 to -0.03), hemoglobin (FXIII level, -0.05 U/mL; 95% CI, -0.07 to -0.03), fibrinogen level (FXIII level, -0.05 U/mL; 95% CI, -0.08 to -0.02), and platelet count (FXIII level, -0.02 U/mL; 95% CI, -0.04 to -0.008)., Conclusions: Baseline FXIII levels in severely injured patients were inconsistently associated with bleeding-related outcomes and mortality. However, their association with major bleeding warrants further investigation of the role of FXIII in massively transfused patients with trauma., Competing Interests: Declaration of competing interests J.C.G.B. reports salary support from the Ministry of Health, Long-Term Care-Clinician Investigator Program, and the Department of Anesthesia and Pain Medicine at the University of Toronto during the completion of this study. J.C. reports research support from the Canadian Blood Services and Octapharma. K.K. reports research support from Octapharma; consultancy fees from Octapharma and Instrumentation Laboratory; and funding in part by merit awarded by the Department of Anesthesia and Pain Medicine, University of Toronto. M.S. is a consultant for Band Therapeutics; receives unrestricted research funding from Pfizer and Octapharma; and receives honoraria from Pfizer, Octapharma, Novartis, and Amgen., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Due to few teaching faculty, resource-limited settings may lack the education curricula providers need for safe practice. As safe surgery becomes an increasing priority worldwide, it is essential to improve access to critical education content including in transfusion medicine. Transfusion Camp is a longitudinal curriculum, shown to increase knowledge in postgraduate trainees. The objective was to develop a sustainable bilateral partnership between Rwanda and Canada, and to integrate Transfusion Camp into the existing curriculum of the School of Medicine and Pharmacy at University of Rwanda., Methods: A Transfusion Camp pilot course was initiated through collaboration of experts in Rwanda and Canada. Planning occurred over 6 months via online and in-person meetings. Canadian teaching faculty adapted course content via iterative discussion with Rwandan faculty. Final content was delivered through online pre-recorded lectures by Canadian Faculty, and in-person small-group seminars by Rwandan Faculty. Project feasibility was assessed through structured evaluation and informal debriefing., Results: Twenty-seven postgraduate trainees were present for the pilot course, of whom 21 (78%) submitted evaluation forms. While the structure and content of the adapted Transfusion Camp curriculum were well-received, the majority of respondents indicated a preference for in-person rather than pre-recorded lectures. Debriefing determined that future courses should focus on continuing education initiatives aimed at physicians entering or already in independent practice., Conclusion: A partnership between universities and blood operators in high-resource and resource-limited countries results in a transfusion medicine curriculum that is locally applicable, multidisciplinary, and supportive of learning benefitting the learners and educators alike., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Purpose: Cold-stored platelets (CSP) are an increasingly active topic of international research. They are maintained at 1-6 °C, in contrast to standard room-temperature platelets (RTP) kept at 20-24 °C. Recent evidence suggests that CSP have superior hemostatic properties compared with RTP. This narrative review explores the application of CSP in adult cardiac surgery, summarizes the preclinical and clinical evidence for their use, and highlights recent research., Source: A targeted search of MEDLINE and other databases up to 24 February 2022 was conducted. Search terms combined concepts such as cardiac surgery, blood, platelet, and cold-stored. Searches of trial registries ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were included. Articles were included if they described adult surgical patients as their population of interest and an association between CSP and clinical outcomes. References of included articles were hand searched., Principal Findings: When platelets are stored at 1-6 °C, their metabolic rate is slowed, preserving hemostatic function for increased storage duration. Cold-stored platelets have superior adhesion characteristics under physiologic shear conditions, and similar or superior aggregation responses to physiologic agonists. Cold-stored platelets undergo structural, metabolic, and molecular changes which appear to "prime" them for hemostatic activity. While preliminary, clinical evidence supports the conduct of trials comparing CSP with RTP for patients with platelet-related bleeding, such as those undergoing cardiac surgery., Conclusion: Cold-stored platelets may have several advantages over RTP, including increased hemostatic capacity, extended shelf-life, and reduced risk of bacterial contamination. Large clinical trials are needed to establish their potential role in the treatment of acutely bleeding patients., (© 2023. Canadian Anesthesiologists' Society.)

Background: Canada has high immunoglobulin (IG) product utilization, raising concerns about appropriate utilization, cost and risk of shortages. Currently, there is no national set of standardized IG guidelines, and considerable variations exist among the existing provincial guidelines. The aims of this study were: (1) to compare the existing Canadian provincial guidelines on the use of IG products to identify their consistencies and differences and (2) to examine the existing research in Canada on IG supply and utilization following the establishment of IG guidelines to understand the scope of research and pinpoint the gaps., Methods: A comparative analysis accounted for the differences across provincial IG guidelines. We highlighted similarities and differences in recommendations for medical conditions. A scoping review of citations from MEDLINE, PubMed, Scopus and Embase databases was conducted for studies published from January 01, 2014, to April 12, 2023., Results: While provincial guidelines represented a considerable overlap in the medical conditions delineated and relatively uniform dose calculations, numerous differences were observed, including in recommendation categories, provision of pediatric dosing, and divergent recommendations for identical conditions based on patient demographics. The scoping review identified 29 studies that focused on the use of IG in Canada. The themes of the studies included: IVIG utilization and audits, the switch from IVIG to SCIG, patient satisfaction with IVIG and/or SCIG, the economic impact of self-administered SCIG versus clinically administered IVIG therapy, and the efficacy and cost-effectiveness of alternative medications to IG treatment., Conclusion: The differences in guidelines across provinces and the factors influencing IVIG/SCIG use, patient satisfaction, and cost savings are highlighted. Future research may focus on clarifying costs and comparative effectiveness, exploring factors influencing guideline adherence, and evaluating the impact of updated guidelines on IG use and patient outcomes., (© 2023. Canadian Society of Allergy & Clinical Immunology.)

Competing Interests: Intérêts concurrents: Jeannie Callum a reçu des subventions de recherche de la Société canadienne du sang (qui fabrique et distribue des produits sanguins) et de la société Octapharma (qui fabrique des concentrés de complexe prothrombique et de fibrinogène). Elle fait partie du comité des mises en candidature de l’Association pour l’avancement des traitements par le sang et des biothérapies et des comités de surveillance de la sécurité des données pour l’essai TRACE (Tranexamic Acid for Subdural Hematoma), une étude pilote de l’Université d’Ottawa sur l’acide tranexamique pour la thrombocytopénie hypoproliférative, et l’étude FEISTY (supplément de fibrinogène en traumatologie). Alan Barkun a reçu des honoraires de consultation des sociétés AstraZeneca et Medtronic. Keyvan Karkouti a reçu des subventions de recherche, des honoraires de consultation et autres de la société Octapharma et des honoraires de consultation de la société Werfen (qui fournit des tests de viscoélasticité en contexte clinique). Il fait partie de comités de révision des Instituts de recherche en santé du Canada et de la Fondation des maladies du cœur. Aucun autre intérêt concurrent n’a été déclaré.

Within the wide scope of interstitial lung diseases (ILDs), familial pulmonary fibrosis (FPF) is being increasingly recognized as a specific entity, with earlier onset, faster progression, and suboptimal responses to immunosuppression. FPF is linked to heritable pathogenic variants in telomere-related genes (TRGs), surfactant-related genes (SRGs), telomere shortening (TS), and early cellular senescence. Telomere abnormalities have also been identified in some sporadic cases of fibrotic ILD. Air pollution and other environmental exposures carry additive risk to genetic predisposition in pulmonary fibrosis. We provide a perspective on how these features impact on screening strategies for relatives of FPF patients, interstitial lung abnormalities, ILD multi-disciplinary team (MDT) discussion, and disparities and barriers to genomic testing. We also describe our experience with establishing a familial interstitial pneumonia (FIP) clinic and provide guidance on how to identify patients with telomere dysfunction who would benefit most from genomic testing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stanel, Callum and Rivera-Ortega.)

Humoral antiplatelet factors, such as autoantibodies, are thought to primarily clear platelets by triggering macrophage phagocytosis in immune thrombocytopenia (ITP). However, there are few studies characterizing the capacity and mechanisms of humoral factor-triggered macrophage phagocytosis of platelets using specimens from patients with ITP. Here, we assessed sera from a cohort of 24 patients with ITP for the capacity to trigger macrophage phagocytosis of normal donor platelets and characterized the contribution of humoral factors to phagocytosis. Sera that produced a phagocytosis magnitude greater than a normal human serum mean + 2 standard deviations were considered phagocytosis-positive. Overall, 42% (8/19) of MHC I alloantibody-negative ITP sera were phagocytosis-positive. The indirect monoclonal antibody immobilization of platelet antigens assay was used to detect immunoglobulin G (IgG) autoantibodies to glycoproteins (GP)IIb/IIIa, GPIb/IX, and GPIa/IIa. Autoantibody-positive sera triggered a higher mean magnitude of phagocytosis than autoantibody-negative sera. Phagocytosis correlated inversely with platelet counts among autoantibody-positive patients but not among autoantibody-negative patients. Select phagocytosis-positive sera were separated into IgG-purified and -depleted fractions via protein G and reassessed for phagocytosis. Phagocytosis was largely retained in the purified IgG fractions. In addition, we assessed serum concentrations of C-reactive protein, serum amyloid P, and pentraxin 3 as potential phagocytosis modulators. Pentraxin 3 concentrations correlated inversely with platelet counts among patients positive for autoantibodies. Taken together, sera from approximately half of the patients with ITP studied triggered macrophage phagocytosis of platelets beyond a normal level. An important role for antiplatelet autoantibodies in phagocytosis is supported; a role for pentraxins such as pentraxin 3 may be suggested., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Early resuscitation with blood components or products is emerging as best practice in selected patients with trauma and medical patients; as a result, out-of-hospital transfusion (OHT) programs are being developed based on limited and often conflicting evidence. This study aimed to provide guidance to Canadian critical care transport organizations on the development of OHT protocols., Methods: The study period was July 2021 to June 2022. We used a modified RAND Delphi process to achieve consensus on statements created by the study team guiding various aspects of OHT in the context of critical care transport. Purposive sampling ensured representative distribution of participants in regard to geography and relevant clinical specialties. We conducted 2 written survey Delphi rounds, followed by a virtual panel discussion (round 3). Consensus was defined as a median score of at least 6 on a Likert scale ranging from 1 ("Definitely should not include") to 7 ("Definitely should include"). Statements that did not achieve consensus in the first 2 rounds were discussed and voted on during the panel discussion., Results: Seventeen subject experts participated in the study, all of whom completed the 3 Delphi rounds. After the study process was completed, a total of 39 statements were agreed on, covering the following domains: general oversight and clinical governance, storage and transport of blood components and products, initiation of OHT, types of blood components and products, delivery and monitoring of OHT, indications for and use of hemostatic adjuncts, and resuscitation targets of OHT., Interpretation: This expert consensus document provides guidance on OHT best practices. The consensus statements should support efficient and safe OHT in national and international critical care transport programs., Competing Interests: Competing interests: Brodie Nolan reports research funding from Canadian Blood Services and Physicians’ Services Incorporated Foundation. Andrew Shih reports payments for consulting on educational materials in relation to bleeding management from Octapharma Canada and payments for advisory board participation in relation to clotting factor concentrates from CSL Behring. He has received speaker honoraria from Octapharma Canada and CSL Behring. Octapharma Canada reimbursed travel expenses for attending a meeting for the FARES-II trial comparing clotting factor concentrates to plasma in cardiac surgery. He is vice-chair of the National Advisory Committee on Blood and Blood Products. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Competing Interests: Competing interests: Jeannie Callum has received research funding from Canadian Blood Services (produces and distributes blood components) and Octapharma (manufactures prothrombin complex concentrate and fibrinogen concentrates). She sits on the nominating committee with the Association for the Advancement of Blood & Biotherapies, and on the data safety monitoring boards for the TRACE (Tranexamic Acid for Subdural Hematoma) trial, a University of Ottawa pilot study of tranexamic acid for hypoproliferative thrombocytopenia, and the FEISTY (fibrinogen replacement in trauma) trial. Alan Barkun has received reimbursement for consulting from AstraZeneca and Medtronic. Keyvan Karkouti has received research funding, consulting fees and honoraria from Octapharma, and consulting fees from Werfen (provides viscoelastic point of care testing). He sits on review boards with the Canadian Institutes of Health Research and the Heart and Stroke Foundation. No other competing interests were declared.

Background: The management of severe hemorrhage has changed significantly over recent decades, resulting in a heterogeneous description of diagnosis, treatment, and outcomes in the literature, which is not suitable for data pooling. Therefore, we sought to develop a core outcome set (COS) to help guide future massive transfusion (MT) research and overcome the challenge of heterogeneous outcomes reporting., Methods: Massive transfusion content experts were invited to participate in a modified Delphi study. For Round 1, participants submitted a list of proposed core outcomes. In subsequent rounds, panelists used a 9-point Likert scale to score proposed outcomes for importance. Core outcomes consensus was defined as >85% of scores receiving 7 to 9 and <15% of scores receiving 1 to 3. Feedback and aggregate data were shared between rounds., Results: From an initial panel of 16 experts, 12 (75%) completed three rounds of deliberation to reevaluate variables not achieving predefined consensus criteria. A total of 64 items were considered, with 4 items achieving consensus for inclusion as core outcomes: blood products received in the first 6 hours, 6-hour mortality, time to mortality, and 24-hour mortality., Conclusion: Through an iterative survey consensus process, content experts have defined a COS to guide future MT research. This COS will be a valuable tool for researchers seeking to perform new MT research and will allow future trials to generate data that can be used in pooled analyses with enhanced statistical power., Level of Evidence: Diagnostic Test or Criteria; Level V., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The optimal method of postgraduate transfusion medicine (TM) education remains understudied. One novel approach is Transfusion Camp, a longitudinal 5-day program that delivers TM education to Canadian and international trainees. The purpose of this study was to determine the self-reported impact of Transfusion Camp on trainee clinical practice., Study Design and Methods: A retrospective analysis of anonymous survey evaluations from Transfusion Camp trainees over three academic years (2018-2021) was conducted. Trainees were asked, "Have you applied any of your learning from Transfusion Camp into your clinical practice?". Through an iterative process, responses were categorized into topics according to program learning objectives. The primary outcome was the rate of self-reported impact of Transfusion Camp on clinical practice. Secondary outcomes were to determine impact based on specialty and postgraduate year (PGY)., Results: Survey response rate was 22%-32% over three academic years. Of 757 survey responses, 68% of respondents indicated that Transfusion Camp had an impact on their practice, increasing to 83% on day 5. The most frequent areas of impact included transfusion indications (45%) and transfusion risk management (27%). Impact increased as PGY increased with 75% of PGY-4+ trainees reporting impact. In multivariable analysis, the impact of specialty and PGY varied depending on the objective., Discussion: The majority of trainees report applying learnings from Transfusion Camp to their clinical practice with variations based on PGY and specialty. These findings support Transfusion Camp as an effective means of TM education and help identify high-yield areas and gaps for future curriculum planning., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Postpartum haemorrhage (PPH) is a leading cause of maternal morbidity and mortality. While tranexamic acid (TXA) reduces bleeding and transfusion requirements in established PPH, we sought to determine the feasibility of conducting a fully powered trial assessing the effect of prophylactic tranexamic acid, prior to PPH onset, in a Canadian Obstetric setting. With institutional and Health Canada approval, consenting, eligible parturients (singleton, > 32 weeks gestation, vaginal or caesarian delivery) were randomly assigned to receive TXA (1 g intravenously) or placebo (0.9% saline) prior to delivery. Participants, investigators, data collectors/adjudicators, and analysis was blinded. The primary outcome was administration of study intervention to > 85% of randomized individuals. Secondary outcomes included recruitment rate (feasibility) and safety outcomes. Over 8 months, 611 were approached, 35 consented, and 27 randomized (14 TXA, 13 placebo). 89% of randomized participants received the assigned intervention. Recruitment fell below feasibility (23% target). No serious adverse outcomes occurred. Our pilot trial in a Canadian Obstetric setting was unable to demonstrate feasibility to conduct a large, multicentre trial to examine prophylactic use of tranexamic for PPH secondary to the complex regulatory requirements associated with a trial for an off-label, but commonly utilized intervention. These challenges should inform stakeholders on the resources and challenges of conducting future trials using off-label interventions.Trial registration: www.clinicaltrials.gov , NCT03069859 (03/03/2017)., (© 2023. The Author(s).)

Importance: Excessive bleeding requiring fibrinogen replacement is a serious complication of cardiac surgery. However, the relative cost-effectiveness of the 2 available therapies-fibrinogen concentrate and cryoprecipitate-is unknown., Objective: To determine cost-effectiveness of fibrinogen concentrate vs cryoprecipitate for managing active bleeding in adult patients who underwent cardiac surgery., Design, Setting, and Participants: A within-trial economic evaluation of the Fibrinogen Replenishment in Surgery (FIBERS) randomized clinical trial (February 2017 to November 2018) that took place at 4 hospitals based in Ontario, Canada, hospitals examined all in-hospital resource utilization costs and allogeneic blood product (ABP) transfusion costs incurred within 28 days of surgery. Participants included a subset of 495 adult patients from the FIBERS trial who underwent cardiac surgery and developed active bleeding and acquired hypofibrinogenemia requiring fibrinogen replacement., Interventions: Fibrinogen concentrate (4 g per dose) or cryoprecipitate (10 units per dose) randomized (1:1) up to 24 hours postcardiopulmonary bypass., Main Outcomes and Measures: Effectiveness outcomes included number of ABPs administered within 24 hours and 7 days of cardiopulmonary bypass. ABP transfusion (7-day) and in-hospital resource utilization (28-day) costs were evaluated and a multivariable net benefit regression model built for the full sample and predefined subgroups., Results: Patient level costs for 495 patients were evaluated (mean [SD] age 59.2 [15.4] years and 69.3% male.) Consistent with FIBERS, ABP transfusions and adverse events were similar in both treatment groups. Median (IQR) total 7-day ABP cost was CAD $2280 (US dollars [USD] $1697) (CAD $930 [USD $692]-CAD $4970 [USD $3701]) in the fibrinogen concentrate group and CAD $2770 (USD $1690) (IQR, CAD $1140 [USD $849]-CAD $5000 [USD $3723]) in the cryoprecipitate group. Median (interquartile range) total 28-day cost was CAD $38 180 (USD $28 431) $(IQR, CAD $26 350 [USD $19 622]-CAD $65 080 [USD $48 463]) in the fibrinogen concentrate group and CAD $38 790 (USD $28 886) (IQR, CAD $26 180 [USD $19 495]-CAD $70 380 [USD $52 409]) in the cryoprecipitate group. After exclusion of patients who were critically ill before surgery (11%) due to substantial variability in costs, the incremental net benefit of fibrinogen concentrate vs cryoprecipitate was positive (probability of being cost-effective 86% and 97% at $0 and CAD $2000 (USD $1489) willingness-to-pay, respectively). Net benefit was highly uncertain for nonelective and patients with critical illness., Conclusions and Relevance: Fibrinogen concentrate is cost-effective when compared with cryoprecipitate in most bleeding adult patients who underwent cardiac surgery with acquired hypofibrinogenemia requiring fibrinogen replacement. The generalizability of these findings outside the Canadian health system needs to be verified.

Damage-control resuscitation is the standard of care for the hemorrhaging trauma patient. This approach combines rapid hemostasis and early-ratio-based blood product administration. These patients often require initiation of a massive hemorrhage protocol to support the systematic and coordinated delivery of care during this critical phase of resuscitation. Emerging evidence supports that this includes more than blood product administration alone but rather a comprehensive suite of treatments. In this article, we review the existing evidence and provide a pragmatic framework, the 7 Ts of massive hemorrhage protocol, to guide the care of patients with life-threatening traumatic hemorrhage., (Copyright © 2022 Elsevier Inc. All rights reserved.)