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.

Transfusion camp: A retrospective study of self-reported impact on postgraduate trainee transfusion practice.

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.

A data-informed system to manage scarce blood product allocation in a randomized controlled trial of convalescent plasma.

BACKGROUND: Equitable allocation of scarce blood products needed for a randomized controlled trial (RCT) is a complex decision-making process within the blood supply chain. Strategies to improve resource allocation in this setting are lacking. METHODS: We designed a custom-made, computerized system to manage the inventory and allocation of COVID-19 convalescent plasma (CCP) in a multi-site RCT, CONCOR-1. A hub-and-spoke distribution model enabled real-time inventory monitoring and assignment for randomization. A live CCP inventory system using REDCap was programmed for spoke sites to reserve, assign, and order CCP from hospital hubs. A data-driven mixed-integer programming model with supply and demand forecasting was developed to guide the equitable allocation of CCP at hubs across Canada (excluding Québec). RESULTS: 18/38 hospital study sites were hubs with a median of 2 spoke sites per hub. A total of 394.5 500-ml doses of CCP were distributed; 349.5 (88.6%) doses were transfused; 9.5 (2.4%) were wasted due to mechanical damage sustained to the blood bags; 35.5 (9.0%) were unused at the end of the trial. Due to supply shortages, 53/394.5 (13.4%) doses were imported from Héma-Québec to Canadian Blood Services (CBS), and 125 (31.7%) were transferred between CBS regional distribution centers to meet demand. 137/349.5 (39.2%) and 212.5 (60.8%) doses were transfused at hubs and spoke sites, respectively. The mean percentages of total unmet demand were similar across the hubs, indicating equitable allocation, using our model. CONCLUSION: Computerized tools can provide efficient and immediate solutions for equitable allocation decisions of scarce blood products in RCTs.

Babesia microti in a Canadian blood donor and lookback in a red blood cell recipient.

BACKGROUND AND OBJECTIVES: We describe the third documented case of autochthonous human babesiosis in Canada and the second in a Canadian blood donor. MATERIALS AND METHODS: Multiple laboratory investigations were carried out on the donor and the immunocompromised recipient of an associated, potentially infectious red blood cell product. RESULTS: The donor had not travelled except for outdoor exposure in south-eastern Manitoba, followed by illness and hospital admission. The donor had a notable parasitaemia, positive for Babesia microti using whole blood nucleic acid testing (NAT). The recipient was negative for B. microti by both serology and NAT. CONCLUSION: There was no evidence of transfusion-transmitted babesiosis.

The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study.

BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

A prospective multi-faceted interventional study of blood bank technologist screening of red blood cell transfusion orders: The START study.

BACKGROUND: Transfusion of red blood cells (RBC) is a common procedure, which when prescribed inappropriately can result in adverse patient outcomes. This study sought to determine the impact of a multi-faceted intervention on unnecessary RBC transfusions at hospitals with a baseline appropriateness below 90%. STUDY DESIGN AND METHODS: A prospective medical chart audit of RBC transfusions was conducted across 15 hospitals. For each site, 10 RBCs per month transfused to inpatients were audited for a 5-month pre- and 10-month post-intervention period, with each transfusion adjudicated for appropriateness based on pre-set criteria. Hospitals with appropriateness rates below 90% underwent a 3-month intervention which included: adoption of standardized RBC guidelines, staff education, and prospective transfusion order screening by blood bank technologists. Proportions of RBC transfusions adjudicated as appropriate and the total number of RBC units transfused per month in the pre- and post-intervention period were examined. RESULTS: Over the 15-month audit period, at the 13 hospital sites with a baseline appropriateness below 90%, 1950 patients were audited of which 81.2% were adjudicated as appropriate. Proportions of appropriateness and single-unit orders increased from 73.5% to 85% and 46.2% to 68.2%, respectively from pre- to post-intervention (P < .0001). Pre- and post-transfusion hemoglobin levels and the total number of RBCs transfused decreased from baseline (P < .05). The median pre-transfusion hemoglobin decreased from a baseline of 72.0 g/L to 69.0 g/L in the post-intervention period (P < .0001). RBC transfusions per acute inpatient days decreased significantly in intervention hospitals, but not in control hospitals (P < .001). The intervention had no impact on patient length of stay, need for intensive care support, or in-hospital mortality. CONCLUSION: This multifaceted intervention demonstrated a marked improvement in RBC transfusion appropriateness and reduced overall RBC utilization without impacts on patient safety.

Transfusion Camp: a prospective evaluation of a transfusion education program for multispecialty postgraduate trainees.

BACKGROUND: The optimal method of providing transfusion medicine (TM) education has not been determined. Transfusion Camp was established in 2012 at the University of Toronto as a centrally delivered TM education program for postgraduate trainees. The impact of Transfusion Camp on knowledge, attitudes, and self-reported behavior was evaluated. METHODS: Didactic lectures (delivered locally, by webinar, or recorded) and locally facilitated team-based learning seminars were delivered over 5 days during the academic year to 8 sites: 7 in Canada and 1 in the United Kingdom. Knowledge assessment using a validated 20-question multiple-choice exam was conducted before and after Transfusion Camp. Attitudes and self-reported behavior were collected through a survey. RESULTS: Over 2 academic years (July 2016 to June 2018), 390 trainees from 16 different specialties (predominantly anesthesia, 41%; hematology, 14%; and critical care, 7%) attended at least 1 day of Transfusion Camp. The mean pretest score was 10.3 of 20 (±2.9; n = 286) compared with posttest score of 13.0 (±2.8; n = 194; p < 0.0001). Lower pretest score and greater attendance (4-5 days compared with 1-3 days) were associated with larger improvement in posttest score; delivery format, specialty, and postgraduate year were not. Trainees reported an improvement in self-rated abilities to manage TM scenarios; 95% rated TM knowledge as very or extremely important in providing patient care; and 81% indicated that they had applied learning from Transfusion Camp into clinical practice. CONCLUSIONS: Transfusion Camp increased TM knowledge, fostered a positive attitude toward TM, and enabled a self-reported positive impact on transfusion practice in postgraduate trainees. It is a novel and scalable approach to delivering TM education.

Sex-mismatched red blood cell transfusions and mortality: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Selection of a compatible red blood cell (RBC) unit does not include matching for donor sex. This systematic review and meta-analysis aims to summarize the evidence examining the impact of sex-mismatched RBC transfusion on recipient mortality. MATERIALS AND METHODS: Ovid MEDLINE, Ovid EMBASE, CINAHL, PubMed, Web of Science and the Cochrane Database of Systematic Reviews were searched from inception up to 23 November 2018. Randomized controlled trials and observational studies were included in the search. Eligible studies reported on the impact of sex-matched compared to sex-mismatched RBC transfusion on recipient mortality. Two investigators independently extracted data and assessed study quality. A three-level meta-analytic model was applied to emphasize the unknown dependence among the effect sizes. RESULTS: Five retrospective observational studies (n = 86 737) were included; no RCTs were found. Sex-mismatched RBC transfusions were associated with a higher risk of death compared with sex-matched transfusions (pooled hazard ratio [HR]: 1·13; 95% confidence interval [CI]: 1·02-1·24). In the subgroup of cardiovascular surgery (n = 57 712), there was no significant increase in mortality with sex-mismatched transfusions (pooled HR: 1·08; 95% CI: 0·95-1·22). The data were prone to confounding, selection bias and reporting bias. Certainty of the evidence was very low. CONCLUSION: Sex-mismatched RBC transfusions were associated with an increased risk of death in this pooled analysis. However, the certainty of the evidence was very low from observational studies. The need to match donor and recipient sex for transfusions requires further investigation because of the potential widespread impact.

Chloride and Other Electrolyte Concentrations in Commonly Available 5% Albumin Products.

OBJECTIVE: Use of hyperchloremic IV fluids for resuscitation in sepsis may be associated with increased mortality and use of renal replacement therapy. After crystalloids, 5% human albumin represents the second most common resuscitation fluid in the ICU. Its chloride concentration is rarely considered in the clinical setting. This study quantifies previously undocumented chloride concentrations of three 5% albumin solutions using biochemical analysis. DESIGN: We performed blinded analysis of the electrolyte concentration of albumin samples obtained directly from the national blood supplier (Canadian Blood Services). Two-tailed independent t tests were performed for all possible comparative analyses. Analysis of variance testing was performed for relevant three-way comparisons. Significance threshold was set at p less than 0.05. SETTING: All samples were analyzed in the core laboratory at an academic hospital associated with McMaster University in Hamilton, Ontario, Canada. SUBJECTS: We analyzed 65 albumin samples from three available brands obtained through Canadian Blood Services. They include Plasbumin (n = 21), Alburex (n = 24), Octalbin (n = 20). INTERVENTION: Laboratory technologists blinded to product identification measured the concentration of electrolytes, extended electrolytes, lactate, and albumin of each sample using the Abbott ARCHITECT c8000 chemistry analyzer. MEASUREMENTS AND MAIN RESULTS: The mean chloride concentration of Plasbumin, Alburex, and Octalbin, respectively, were 109.4 mmol/L (SD, 1.3), 123.6 mmol/L (SD, 1.3), and 136.8 mmol/L (SD, 0.4). The mean sodium concentration of Plasbumin, Alburex, and Octalbin, respectively, were 139.6 mmol/L (SD, 1.6), 137.3 mmol/L (SD, 2.2), and 149.4 mmol/L (SD, 0.5). The chloride and sodium concentration differed significantly for all two-way comparisons (p < 0.0001) and multiple comparison testing (p < 0.0001). CONCLUSION: This study is the first to identify and document a statistically significant variability in the chloride concentration of available 5% albumin products. This study has also informed a pilot randomized controlled trial examining the effect of administering high chloride versus low chloride fluids in critically ill patients with sepsis.

An international investigation into AB plasma administration in hospitals: how many AB plasma units were infused? The HABSWIN study.

BACKGROUND: Typical practice is to transfuse group-specific plasma units; however, there are situations where group AB plasma (universal donor) is issued to group A, B, or O recipients. If demand for group AB plasma exceeds collections, there is potential for shortage. This project explored the patterns of group AB plasma utilization at hospitals around the world. STUDY DESIGN AND METHODS: The study had two phases: a survey that inquired about hospital group AB plasma inventory, policies, and transfusion practices and a retrospective review of 2014 calendar year data where participants submitted information on plasma disposition including ABO group of unit and recipient, transfusion location, and select indications. Recruitment occurred through snowball sampling. Descriptive analyses were performed. RESULTS: Survey data were received from 25 centers across 10 countries; of those, 15 participants contributed to the data collection component. These 15 centers transfused a total of 43,369 AB plasma units during the study period. Only 1496 of 5541 (27%) group AB plasma units were transfused to group AB recipients. Transfusion policies, practices, and patterns were variable across sites. CONCLUSION: Group AB plasma units are frequently transfused to non-AB recipients. Whether transfusing 73% of group AB plasma units to non-AB recipients is the ideal inventory management strategy remains to be determined.

Paroxysmal cold hemoglobinuria: a difficult diagnosis in adult patients.

BACKGROUND: Paroxysmal cold hemoglobinuria (PCH) is a rare form of autoimmune hemolytic anemia caused by a biphasic (Donath-Landsteiner [DL]) immunoglobulin G autoantibody. Estimates of disease frequency after syphilis are lacking and the diagnostic yield of testing for PCH is uncertain. The objectives of this study were: 1) to describe DL testing practices in Canada, 2) to determine how often a biphasic RBC antibody is detected in adults and children, and 3) to evaluate inter-rater reliability of interpretations of positive DL test results in adults. STUDY DESIGN AND METHODS: We performed a national survey of reference laboratories, chart review of all test-positive cases, and independent panel adjudication. RESULTS: Of 18 reference laboratories invited, 14 participated in the survey. In a representative year, 52 DL tests were requested across 14 centers, a region that serves more than 60% of Canada's population. In 124 cumulative testing-years, three positive tests were reported in adults and 14 positive tests were reported in children. There was poor agreement on interpretation of the three positive test results in adults among a panel of four experts (Fleiss κ = -0.1852; standard error, 0.1309; 95% confidence interval, -0.4418 to 0.0715). At a large academic center, 34 samples from 27 patients were sent for DL testing from 2006 to 2013 with 97% (33/34) reported as negative, inconclusive, or unacceptable samples. CONCLUSION: Positive DL test results are rare and occur more commonly in children than adults. There was poor agreement among experts on the interpretation of a positive DL test in adults. These observations highlight the difficulties in establishing the diagnosis of PCH in adults and calls for scrutiny of current laboratory practice.

An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study.

BACKGROUND: Transfusion of group O blood to non-O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices. STUDY DESIGN AND METHODS: This was a retrospective study on transfusion data from the 2013 calendar year. This study included a survey component that asked about hospital RBC selection and transfusion practices and a data collection component where participants submitted information on RBC unit disposition including blood group and D type of unit and recipient. Units administered to recipients of unknown ABO or D group were excluded. RESULTS: Thirty-eight hospitals in 11 countries responded to the survey, 30 of which provided specific RBC unit disposition data. Overall, 11.1% (21,235/191,397) of group O units were transfused to non-O recipients; 22.6% (8777/38,911) of group O D- RBC units were transfused to O D+ recipients, and 43.2% (16,800/38,911) of group O D- RBC units were transfused to recipients that were not group O D-. Disposition of units and hospital transfusion policy varied within and across hospitals of different sizes, with transfusion of group O D- units to non-group O D- patients ranging from 0% to 33%. CONCLUSION: A significant proportion of group O and D- RBC units were transfused to compatible, nonidentical recipients, although the frequency of this practice varied across sites.

Effect of a thrombopoietin receptor agonist on use of intravenous immune globulin in patients with immune thrombocytopenia.

BACKGROUND: Thrombopoietin receptor agonists are new treatments for patients with chronic immune thrombocytopenia (ITP). How one of these agent, romiplostim, has impacted practice patterns, especially the use of intravenous immune globulin (IVIG), has not been evaluated outside of clinical trials. STUDY DESIGN AND METHODS: This was a retrospective cohort study of adult ITP patients treated with romiplostim in four Canadian centers. Patients had primary or secondary ITP and were followed for 1 year before starting weekly romiplostim treatment. We compared IVIG use, clinical outcomes, and cost before and after romiplostim. RESULTS: Twenty-nine patients with ITP received romiplostim. Median age was 54 years (interquartile range [IQR], 45-63 years) and patients had a median of two prior ITP treatments (IQR, 1-4) including splenectomy (n = 7). Median platelet (PLT) count was 23 × 10(9) before and 124 × 10(9) after romiplostim. Median duration of romiplostim treatment was 3.7 months. Patients used a median of two IVIG infusions per year before and 0.7 per year after starting romiplostim (p = 0.16). For patients who received weekly romiplostim for at least 1 month (n = 19), IVIG infusions were three (IQR, 1-5) per year before and 0.7 (IQR, 0.4-1.6) per year after romiplostim. Results were squewed by two high IVIG users. Nineteen (66%) patients discontinued romiplostim treatment during follow-up because of lack of response (n = 8), sustained response (n = 5), toxicities (n = 4), or response to splenectomy (n = 2). Overall health care costs were similar before and after romiplostim when concomitant treatments, nursing resources, and hospitalizations were considered. CONCLUSIONS: Romiplostim was associated with improved PLT counts and fewer IVIG infusions for most ITP patients. In practice, romiplostim was generally not continued long term and was cost neutral for overall ITP management.

Prophylactic platelet transfusions: should they be a treatment of the past?

PURPOSE OF REVIEW: For decades, prophylactic platelet transfusions have been a standard practice for treatment-related thrombocytopenia in patients with hematologic malignancies, although evidence supporting this practice was limited. Two recent randomized controlled studies were carried out to challenge this practice by comparing prophylactic to therapeutic-only platelet transfusion strategies. This review compares and contrasts the study findings to provide further insight into the study conclusions and their application to practice. RECENT FINDINGS: Past studies exploring platelet transfusion in this patient population focused on identifying the optimal platelet threshold for transfusions and the minimum effective dose to achieve hemostasis. Balancing increased demand with limited supply has further necessitated determining if a therapeutic-only approach is as efficacious. This is especially pertinent given improved prognosis of hematologic malignancies because of novel therapies and better diagnostic technologies. Two large randomized controlled studies showed that therapeutic-only strategy reduces platelet utilization, but possibly at an increased risk of high-grade bleeding in certain patient groups. SUMMARY: The majority of this adult patient population should continue to receive prophylactic platelet transfusions to prevent high-grade bleeding. Stable autologous stem cell transplant patients appear to be at a lower risk of thrombocytopenia-related bleeding and are candidates for therapeutic-only platelet transfusions in expert centers with careful monitoring.

Learning From Clinical Supervisor Practice Variability: Exploring Medical Resident and Fellow Experiences and Interpretations.

PURPOSE: Clinical practice variability is characterized by 2 or more clinicians making different treatment decisions despite encountering a similar case. This study explores how medical residents and fellows experience and interpret intersupervisor clinical practice variability and how these variations influence learning. METHOD: Seventeen senior residents or fellows in internal medicine, hematology, or thrombosis medicine (postgraduate year 3 or above) participated in semistructured interviews after a clinical rotation in thrombosis medicine from December 2019 to March 2021. Data collection and analysis occurred iteratively and concurrently in a manner consistent with constructivist grounded theory. Variation theory was used to guide the development of some interview questions. A central tenet of this theory is that learning occurs by experiencing 3 sequential patterns of variation: contrast, generalization, and fusion. Participants were recruited purposively with respect to specialty until theoretical sufficiency was reached. RESULTS: Clinical practice variability was experienced by all participants. Residents and fellows attributed practice variability to intrinsic differences among supervisors; interinstitutional differences; selection and interpretation of evidence; patient preferences, priorities, and fears; and their own participation in the decision-making process. Clinical practice variability helped residents and fellows discern key features of cases that influenced decision-making (contrast), group similar cases so that the appropriate evidence could be applied (generalization), and develop attitudes consistent with providing individualized patient care (fusion). Observing practice variability was more helpful for fifth- and sixth-year residents and less helpful for third- and fourth-year residents. CONCLUSIONS: Clinical practice variability helped residents and fellows discern critical aspects, group similar patients, and practice individualized medicine. Future research should characterize how clinical practice variability influences learning across the spectrum of training, how supervisors could encourage learning from practice variability, and how curricula could be modified to allow learners greater opportunity to reflect on and consolidate the practice differences they observe.

Optimizing Informed Consent Discussions: Developing a Narrative for Transfusion Consent.

Ensuring patient informed consent is a key tenet of modern medicine. Although transfusion of blood products is among the most common medical procedures performed in hospitalized patients, there is evidence that informed consent for transfusion is at times incomplete, poorly understood, hurried, and/or inaccurate. This study aimed to develop a narrative that can be used as a framework for practicing physicians and for educational purposes to optimize the process for obtaining informed consent for blood transfusion. The narrative was developed using a modified Delphi approach with 5 Rounds that included feedback from transfusion medicine (TM) experts, transfusion-provider physicians, and lay people. The surveys collected qualitative and quantitative data analyzed using thematic content analysis and descriptive statistics, respectively. Results from Rounds 1 and 2 generated a draft narrative and Rounds 3 to 5 informed further modifications. Round 1 included draft narrative scripts from 28 TM experts; thematic coding generated 97 topics. In round 2, 22/28 of the initial experts rated items identified from Round 1. Those with a content validity index (CVI) ≥ 0.8 were used by the authors to develop a narrative. In Round 3, 20/24 participants from Round 2 reviewed the narrative with 100% agreeing on the items included and 90% agreeing the flow was logical. In Round 4, 23 transfusion prescribers (non-TM physicians) reviewed the narrative for flow, manner, length, and usability; there was 83% agreement with the nonexclusion of important topics; 91% felt it would be effective for teaching trainees. Round 5 included 24 nonmedical laypeople of different demographics. Most participants (92%) thought that the script was appropriate in length and there were opportunities to ask questions. Participants could also identify the adverse transfusion reactions and understand that they could refuse the transfusion. A narrative for obtaining informed consent for blood transfusion was created through multiple rigorous iterations of review and feedback with both transfusion providers and the lay public. The narrative, developed for a specific clinical scenario, was well-received by medical and nonmedical participants and can be used, and modified, to help ensure patients understand the risks and benefits of blood transfusion.

Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.

BACKGROUND: Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care. METHODS: We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices. DISCUSSION: This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019137282.