Opportunities to improve feedback to reduce blood component wastage: Results of a national scheme evaluation.

BACKGROUND: Blood components are costly and scarce. The Blood Stocks Management Scheme (BSMS) was established in the United Kingdom (UK) to support hospital transfusion services and national blood services through collection, analysis, and monthly feedback of data on blood component inventory and wastage management. There is a growing evidence base on how best to deliver feedback for quality improvement. We assessed the quality and utility of the monthly BSMS component reports. METHODS: We assessed the content of BSMS reports issued in March 2023 against established criteria for effective feedback. Two researchers independently rated whether criteria spanning the five domains of goal setting, data collection, feedback content, feedback display and feedback delivery were fully, partially or not met. Disagreements were resolved through discussion. We conducted an online questionnaire survey of recipients of BSMS reports during March 2023 to assess their use of reports and seek suggestions for improvement. RESULTS: Five out of 20 criteria for effective feedback were fully met. Areas for improvement included placing more emphasis in the feedback on positive change, linking data and summary messages, and including specific suggestions for action. Respondents highlighted the value of benchmarked comparisons with other hospital transfusion services. CONCLUSION: There is scope for enhancing the effectiveness and utility of BSMS feedback reports and hence reducing wastage of blood components. This methodology for evaluation of feedback could be utilized to improve other areas of transfusion practice.

Rethinking the transfusion pathway in myelodysplastic syndromes: Study protocol for a novel randomized feasibility n-of-1 trial of weekly-interval red cell transfusion in myelodysplastic syndromes.

BACKGROUND: Anemia in myelodysplastic syndromes (MDS) is associated with poorer health-related quality of life (HRQoL) and physical function, and is frequently treated with transfusions. The current common practice of transfusing multiple red blood cells (RBC) units every 2-4 weeks may result in peaks/troughs in hemoglobin (Hb) level, yet maintaining a stable Hb may better improve HRQoL. We describe a study protocol aiming to investigate the feasibility of weekly low-dose RBC transfusion in MDS patients, including assessing HRQoL and physical function outcomes. STUDY DESIGN AND METHODS: In this n-of-1 pilot study, patients receive two treatment arms, with randomly allocated treatment sequence: arm A (patient's usual transfusion schedule) and arm B (weekly transfusion, individualized per patient). To facilitate timely delivery of weekly transfusion, extended-matched RBCs are provided, with transfusion based upon the previous week's Hb/pre-transfusion testing results to eliminate delays of awaiting contemporaneous cross-matching. Primary outcome is the feasibility of delivering weekly transfusion. Secondary outcomes include HRQoL, functional activity measurements, RBC usage, and alloimmunization rates. A qualitative substudy explores patient and staff experiences. RESULTS: The trial is open in Australia, Netherlands, and UK. The first patient was recruited in 2020. Inter-country differences in providing RBCs are observed, including patient genotyping versus serological phenotyping to select compatible units. DISCUSSION: This pilot trial evaluates a novel personalized transfusion approach of weekly matched RBC transfusion and challenges the dogma of current routine pre-transfusion matching practice. Findings on study feasibility, HRQoL, and physical functional outcomes and the qualitative substudy will inform the design of a larger definitive trial powered for clinical outcomes.

A review and analysis of outcomes in randomized clinical trials of plasma transfusion in patients with bleeding or for the prevention of bleeding: The BEST collaborative study.

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.

Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Results of a pilot randomized trial RBC-ENHANCE.

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.

E-learning in transfusion medicine: An exploratory qualitative assessment.

BACKGROUND AND OBJECTIVES: E-learning programmes are increasingly offered in transfusion medicine (TM) education. The aim of this study was to explore facilitators and barriers to TM e-learning programmes, including assessment of learning outcomes and measures of effectiveness. MATERIALS AND METHODS: Participants selected from a prior survey and representing a diverse number of international e-learning programmes were invited to participate. A mixed methodology was employed, combining a survey and individual semi-structured one-on-one interviews. Interview data were analysed inductively to explore programme development, evaluation, and facilitators and barriers to implementation. RESULTS: Fourteen participants representing 13 institutions participated in the survey and 10 were interviewed. The e-learning programmes have been in use for a variable duration between 5 and 16 years. Funding sources varied, including government and institutional support. Learner assessment methods varied and encompassed multiple-choice-questions (n = 12), direct observation (n = 4) and competency assessment (n = 4). Most regional and national blood collection agencies rely on user feedback and short-term learning assessments to evaluate their programmes. Only one respondent indicated an attempt to correlate e-learning with clinical practices. Factors that facilitated programme implementation included support from management and external audits to ensure compliance with regulatory educational and training requirements. Barriers to programme implementation included the allocation of staff time for in-house development, enforcing compliance, keeping educational content up-to-date and gaining access to outcome data for educational providers. CONCLUSION: There is evidence of considerable diversity in the evaluation of e-learning programmes. Further work is needed to understand the ultimate impact of TM e-learning on transfusion practices and patient outcomes.

Iron Deficiency in Anemic Children Surviving Critical Illness: Post Hoc Analysis of a Single-Center Prospective Cohort in Canada, 2019-2022.

OBJECTIVES: Many children leave the PICU with anemia. The mechanisms of post-PICU anemia are poorly investigated, and treatment of anemia, other than blood, is rarely started during PICU. We aimed to characterize the contributions of iron depletion (ID) and/or inflammation in the development of post-PICU anemia and to explore the utility of hepcidin (a novel iron marker) at detecting ID during inflammation. DESIGN: Post hoc analysis of a single-center prospective study (November 2019 to September 2022). SETTING: PICU, quaternary center, Canada. PATIENTS: Children admitted to PICU with greater than or equal to 48 hours of invasive or greater than or equal to 96 hours of noninvasive ventilation. We excluded patients with preexisting conditions causing anemia or those admitted after cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hematological and iron profiles were performed at PICU discharge on 56 participants of which 37 (37/56) were diagnosed with anemia. Thirty-three children (33/56; 59%) were younger than 2 years. Median Pediatric Logistic Organ Dysfunction score was 11 (interquartile range, 6-16). Twenty-four of the 37 anemic patients had repeat bloodwork 2 months post-PICU. Of those, four (4/24; 16%) remained anemic. Hematologic profiles were categorized as: anemia of inflammation (AI), iron deficiency anemia (IDA), IDA with inflammation, and ID (low iron stores without anemia). Seven (7/47; 15%) had AI at discharge, and one had persistent AI post-PICU. Three patients (3/47; 6%) had IDA at discharge; of which one was lost to follow-up and the other two were no longer anemic but had ID post-PICU. Eleven additional patients developed ID post-PICU. In the exploratory analysis, we identified a diagnostic cutoff value for ID during inflammation from the receiver operating characteristic curve for hepcidin of 31.9 pg/mL. This cutoff would increase the detection of ID at discharge from 6% to 34%. CONCLUSIONS: The burden of ID in children post-PICU is high and better management strategies are required. Hepcidin may increase the diagnostic yield of ID in patients with inflammation.

Small-volume blood sample collection tubes in adult intensive care units: A rapid practice guideline.

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.

Impact of patient demographics on treatment outcomes in AML: a population-based registry in England, 2013-2020.

We report 1- and 5-year survival following AML diagnosis and early mortality, within 30 days of systemic anti-cancer therapy (SACT) treatments, using national cancer registry data in England. Patients aged 18-99 years diagnosed between 2013 and 2020 were included. Overall survival (OS) was calculated using Kaplan-Meier methodology and hazard ratios (aHRs, adjusted for intensity of treatment, age at diagnosis, gender, ethnicity, socioeconomic deprivation, comorbidity, and year of diagnosis) using Cox proportional hazards regression. Odds of 30-day mortality (aORs, adjusted for characteristics listed above, along with performance status (PS) and body mass index (BMI), were calculated using logistic regression. Amongst 17107 patients identified, older age and comorbidity were associated with worse survival. Asian and Black patients had better survival than White: 5-year OS 34.6%, 29.7%, and 17.8%; aHR 0.86 (95% CI 0.77-0.96) Asian vs White, and 0.84 (0.73-0.96) Black vs White. Socioeconomic deprivation was associated with worse survival. 7906 (46.2%) patients were documented as having received SACT. 30-day mortality was lower for patients receiving intensive rather than non-intensive SACT. After adjustment for co-factors the risk was higher in those treated intensively (aOR 0.74 [95% CI 0.60-0.92]). We show that ethnicity and socio-economic status impacts outcomes in AML. Further work is needed to understand how these effects may differ in different healthcare settings, and whether this due to effects on disease biology, responsiveness to treatment or drug toxicity. Selection of intensive vs non-intensive treatment should be based on individual patient factors, balancing improved long-term survival against higher early mortality.

Clinical Practice Guideline for Red Blood Cell Transfusion Thresholds in Very Preterm Neonates.

Importance: Red blood cell (RBC) transfusion is a common medical intervention to treat anemia in very preterm neonates; however, best transfusion practices, such as thresholds, remain uncertain. Objective: To develop recommendations for clinicians on the use of RBC transfusions in very preterm neonates. Evidence Review: An international steering committee reviewed evidence from a systematic review of 6 randomized clinical trials (RCTs) that compared high vs low hemoglobin-based or hematocrit-based transfusion thresholds. The steering committee reached consensus on certainty-of-evidence ratings and worked with a panel from stakeholder organizations on reviewing the evidence. With input from parent representatives and the stakeholder panel, the steering committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to develop recommendations. Findings: A systematic review of 6 RCTs encompassing 3483 participants (1759 females [51.3%]; mean [SD] age range, 25.9-29.8 [1.5-3.0] weeks) was used as the basis of the recommendations. The ranges for higher hemoglobin concentration (liberal) vs lower hemoglobin concentration (restrictive) threshold study arms were similar across the trials. However, specific thresholds differed based on the severity of illness, which was defined using variable criteria in the trials. There was moderate certainty of evidence that low transfusion thresholds likely had little to no difference in important short-term and long-term outcomes. The recommended hemoglobin thresholds varied on the basis of postnatal week and respiratory support needs. At postnatal weeks 1, 2, and 3 or more, for neonates on respiratory support, the recommended thresholds were 11, 10, and 9 g/dL, respectively; for neonates on no or minimal respiratory support, the recommended thresholds were 10, 8.5, and 7 g/dL, respectively (to convert hemoglobin to grams per liter, multiply by 10.0). Conclusions and Relevance: This consensus statement recommends a restrictive RBC transfusion strategy, with moderate certainty of evidence, for preterm neonates with less than 30 weeks' gestation.

Desmopressin for prevention of bleeding for thrombocytopenic, critically ill patients undergoing invasive procedures: A randomised, double-blind, placebo-controlled feasibility trial.

Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 109/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure. Forty-three participants (18.8% of those eligible) were recruited, with 41 eligible for analysis. Post-procedure bleeding occurred in one of 22 (4.5%) in the placebo arm and zero of 19 in the desmopressin arm. Despite liberal inclusion criteria, there were significant feasibility challenges recruiting patients in the critical care setting prior to invasive procedures.

Trauma induced coagulopathy is limited to only one out of four shock induced endotheliopathy (SHINE) phenotypes among moderate-severely injured trauma patients: an exploratory analysis.

BACKGROUND: Trauma induced coagulopathy remains to be an important cause of high transfusion requirements and mortality and shock induced endotheliopathy (SHINE) has been implicated. METHODS: European multicenter observational study of adult trauma patients with injury severity score ≥ 16 arriving within 2 h from injury to the trauma centers. Admission blood samples obtained were used for analysis of the SHINE biomarkers (syndecan-1, soluble thrombomodulin, adrenaline) and extensive analysis of coagulation, -and fibrinolytic factors together with collection of clinical data. Hierarchical clustering of the SHINE biomarkers was used to identify the SHINE phenotypes. RESULTS: The 313 patients clustered into four SHINE phenotypes. Phenotype 2, having the highest glycocalyx shedding, encompassing 22% of the whole cohort, had severe coagulopathy with lower levels of prothrombin, FV, IX, X, XI and severe hyperfibrinolysis with higher plasmin - alpha 2-antiplasmin (PAP) - and tPA levels and lower alpha2 - antiplasmin levels. This phenotype had significantly higher transfusion requirements and higher mortality (39% vs. 23%, 15% and 14%) but similar injury severity score (ISS) compared to the others phenotypes. CONCLUSIONS: Hierarchical clustering identified four SHINE phenotype in a cohort of trauma patients. Trauma induced coagulopathy was confined to only one of the SHINE phenotypes, encompassing 22% of the total cohort. This phenotype was characterized by severe hypocoagulability and hyperfibrinolysis, which translated to significantly higher transfusion requirements and higher mortality compared to the other SHINE phenotypes with similar injury severity, warranting further investigation.