Leading digit bias in hemoglobin thresholds for red cell transfusion.

BACKGROUND: Leading digit bias is a heuristic whereby humans overemphasize the left-most digit when evaluating numbers (e.g., 9.99 vs. 10.00). The bias might affect the interpretation of hemoglobin results and influence red cell transfusion in hospitalized patients. STUDY DESIGN AND METHODS: Adults who received a red cell transfusion while registered at the University Health Network (Toronto, Canada) between January 1, 2016 and January 1, 2022 (n = 6 years) were included. The primary analysis excluded apheresis, red cell disorders, radiology suites, and operating rooms. The primary comparison was a regression discontinuity analysis of transfusion occurrence above and below the hemoglobin threshold of 79 g/L (local units). Additional analyses tested other leading digit and control thresholds (71, 81, and 91 g/L). Secondary analyses explored temporal covariates and clinical subgroups. RESULTS: A total of 211,872 red cell transfusions were identified over the study period (median pre-transfusion hemoglobin 76 g/L; interquartile range = 69-92 g/L), with 107,790 inpatient transfusions in the primary analysis. The 79 g/L threshold showed 815 fewer red cell units above the threshold (95% confidence interval [CI]: -1215 to -415). The 69 g/L threshold showed 2813 fewer transfused units (95% CI: -4407 to -1220), and 89 g/L showed 40 fewer units (95% CI: -408 to 328). The effect was accentuated during daytime, weekday, and May-June months, persisted in analyses including all transfusions, and was absent at control thresholds. CONCLUSION: Leading digit bias might have a modest influence on the decision to transfuse red cells. The findings may inform practice guidelines and quasi-experimental study design in transfusion research.

Current concepts in the use of cell salvage in obstetrics.

PURPOSE OF REVIEW: The worldwide leading cause of maternal death is severe maternal hemorrhage. Maternal hemorrhage can be profound leading to an entire loss of blood volume. In the past two decades, Patient Blood Management has evolved to improve patient's care and safety. In surgeries with increased blood loss exceeding 500 ml, the use of cell salvage is strongly recommended in order to preserve the patient's own blood volume and to minimize the need for allogeneic red blood cell (RBC) transfusion. In this review, recent evidence and controversies of the use of cell salvage in obstetrics are discussed. RECENT FINDINGS: Numerous medical societies as well as national and international guidelines recommend the use of cell salvage during maternal hemorrhage. SUMMARY: Intraoperative cell salvage is a strategy to maintain the patient's own blood volume and decrease the need for allogeneic RBC transfusion. Historically, cell salvage has been avoided in the obstetric population due to concerns of iatrogenic amniotic fluid embolism (AFE) or induction of maternal alloimmunization. However, no definite case of AFE has been reported so far. Cell salvage is strongly recommended and cost-effective in patients with predictably high rates of blood loss and RBC transfusion, such as women with placenta accreta spectrum disorder. However, in order to ensure sufficient practical experience in a multiprofessional obstetric setting, liberal use of cell salvage appears advisable.

Red Blood Cell Transfusion: 2023 AABB International Guidelines.

Importance: Red blood cell transfusion is a common medical intervention with benefits and harms. Objective: To provide recommendations for use of red blood cell transfusion in adults and children. Evidence Review: Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed. Findings: For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence). Conclusions and Relevance: It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness.

BACKGROUNDRBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.METHODSThis is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.RESULTSBlood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours.CONCLUSIONDonor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.FUNDINGFunding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).

Red Blood Cell Transfusion Practices for Patients With Cervical Cancer Undergoing Radiotherapy.

Importance: Packed red blood cell (PRBC) transfusions are used to treat anemia in patients with cervical cancer undergoing radiotherapy (RT) owing to concerns of hypoxia-induced radioresistance. In the absence of high-quality evidence informing transfusion practices for patients receiving external beam RT (EBRT) and brachytherapy, various arbitrary hemoglobin target levels are used worldwide. Objective: To develop consensus statements to guide PRBC transfusion practices in patients with cervical cancer receiving curative-intent RT with EBRT and brachytherapy. Design, Setting, and Participants: This international Delphi consensus study was completed between November 1, 2019, and July 31, 2020. A total of 63 international clinical experts in gynecologic radiation oncology were invited; 39 (62%) accepted and consented to participate. Consensus building was achieved using a 3-round anonymous Delphi consensus method. Participants rated their agreement or disagreement with statements using a 5-point Likert scale. An a priori threshold of 75% or more was required for consensus. Main Outcomes and Measures: The preplanned primary outcome of this study was to assess hemoglobin transfusion thresholds and targets for both EBRT and brachytherapy by expert consensus. Results: Response rates of 100% (39 of 39), 92% (36 of 39), and 97% (35 of 36) were achieved for the first, second, and third rounds of surveys, respectively. Twenty-three experts (59%) practiced in Canada, 11 (28%) in the United States, 3 (8%) in South America, 1 (3%) in Europe, and 1 (3%) in Asia. Consensus was reached for 44 of 103 statements (43%), which were combined to form the final 27-statement consensus guideline. No specific hemoglobin transfusion threshold was agreed on by consensus for EBRT or brachytherapy. By consensus (89% [31 of 35]), a hemoglobin transfusion target for patients who receive a PRBC transfusion should be 9 g/dL or more and less than 12 g/dL. Conclusions and Relevance: This study presents the first international expert consensus guideline informing PRBC transfusion practices for patients with cervical cancer undergoing EBRT and brachytherapy. A minimum hemoglobin transfusion target of 9 g/dL was endorsed to balance tumor radiosensitivity with appropriate use of a scarce resource. Randomized clinical trials are required to evaluate the optimal transfusion threshold and target that maximize clinical benefit in this patient population.

Thrombin Generation Kinetics are Predictive of Rapid Transfusion in Trauma Patients Meeting Critical Administration Threshold.

INTRODUCTION: We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24 h after injury, independent of international normalized ratio (INR). METHODS: In a prospective cohort study, trauma patients were enrolled over a 4.5-year period and serial blood samples collected at various time points. We retrospectively stratified pts into three categories: CAT+, CAT- but receiving some pRBC Tx, receiving no Tx within the first 24 h. Blood collected prior to Tx was analyzed for thrombin generation parameters and prothrombin time (PT)/INR. RESULTS: A total of 484 trauma pts were analyzed: injury severity score = 13 [7,22], age = 48 [28, 64] years, and 73% male. Fifty pts met criteria for CAT+, 64 pts CAT-, and 370 received no Tx. Risk factors for meeting CAT+: decreased arrival systolic blood pressure (OR 2.82 [2.17, 3.67]), increased INR (OR 2.09, [1.66, 2.62]) and decreased time to peak OR 2.27 [1.74, 2.95]). These variables remained independently associated with increased risk of requiring Tx in a multivariable logistic model, after adjusting for sex and trauma type. CONCLUSIONS: Pts in hemorrhagic shock, who meet CAT+ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.

Manual erythroexchange in sickle cell disease: multicenter validation of a protocol predictive of volume to exchange and hemoglobin values.

Manual erythroexchange (MEEX) was proven to be effective and safe in the management of sickle cell disease (SCD). The goal is to quickly reduce the percentage of hemoglobin S (HbS%). A national survey of the Italian Society for Thalassemia and Hemoglobinopathies (SITE) observed a great variability among MEEX protocols none of which were found to be predictive of the values of HbS% and hemoglobin (Hb) after the exchange. Two equations to estimate the HbS% and Hb values to be obtained after MEEX were developed based on the results of the MEEX procedures in place in the centers participating in the present study. A standard protocol was subsequently defined to evaluate the volumes to exchange to obtain the target values of HbS% and Hb. The protocol was tested in 261 MEEX performed in SCD patients followed in the 5 participating centers that belong to the Italian Hemoglobinopathy Comprehensive Care Network, with the support of the SITE. The results showed a correlation between the estimated and measured values of HbS% and Hb (Rp 0.95 and 0.65 respectively, p < 0.001). A negligible bias was found for the prediction of HbS% and a bias of 1 g/dl for Hb. From consecutive MEEX, a rate of increase of HbS% between two exchanges of around 0.4% per day (p < 0.001) was measured. This protocol was shown to be effective and safe, as all patients reached the target value of HbS%. All the MEEX procedures were carried out with single venous access. No adverse events or reactions such as hypotension or electrolyte imbalance were reported nor were any complaints concerning the procedures received from patients.

Differences among hemoglobin thresholds for red blood cell transfusions in patients with hematological diseases in teaching hospitals: a real world data in Japan.

A hemoglobin (Hb) threshold level of 7 g/dL has been proposed for red blood cell (RBC) transfusion in patients with chronic anemia in the Japanese guideline since 2005. However, Hb thresholds for hematological diseases in clinical practice and factors responsible for higher Hb thresholds remain unclear. Hb thresholds were collected for patients with hematological diseases from 32 Japanese teaching hospitals. Uni- and multivariate analyses were used to analyze relationships between Hb threshold level and various patient and hospital factors. In total, 4996 units of RBC were transfused to 1054 patients with hematological diseases in 2421 transfusions. Median age was 68 years. Myelodysplastic syndrome was the most frequent diagnosis. Overall median Hb threshold level was 6.9 g/dL. Multivariate linear regression analysis detected the following variables associated with Hb threshold level: hospital; cardiovascular disease; symptomatic anemia; and hematopoietic stem cell transplantation. Hospital was the most significant factor. Collectively, median Hb threshold level in clinical practice in Japan was similar to the guidelines. Higher Hb threshold level depended on the hospitals at which the transfusions were performed as well as patient condition. Educational approaches directed toward hospitals may be useful to promote transfusion guidelines.

Enhancing the utilization of packed red blood cells stock in maternity hospitals.

OBJECTIVES: To assess and enhance the efficiency of transfusion services in maternity hospitals. METHODS: A case control study was conducted from January to December 2016. A corrective policy of replacing preoperative type and hold step with blood transfusion request (BTR) hold was used only on healthy patients undergoing elective cesarean sections (c-section). The crossmatch/transfusion (C:T) ratio and a cost comparison were the evaluating factors. Data were analyzed using an Excel spreadsheet and SPSS statistical software. RESULTS: A total of 1,200 BTRs were analyzed, comprising 659 before implementation of the corrective policy and 541 blood transfusion requests after implementation of the corrective policy. From January to March, the C:T ratio of c-sections was nearly 7 times the American Association of Blood Banks recommended limit of 2.5. Most of the blood units (94%) were damaged due to repeated booking. After implementation, the cost-e ectiveness of erythrocyte transfusion was greatly enhanced as all the ordered blood units were used and the C:T ratio was reduced to the ideal limit of one. The number of destroyed units was drastically decreased from 450 units to zero; as a result, 83% of the transfusion costs were saved. CONCLUSION: The policy enhances the cost-effectiveness of erythrocyte transfusion and laboratory testing, and saves on additional, unnecessary costs.

Adherence to guidelines on red blood cell transfusions in women having post-partum haemorrhage.

INTRODUCTION: Transfusion of blood products occurs frequently as part of the treatment of post-partum haemorrhage, but since it is both expensive and has potentially severe complications, prescription of blood products should be restricted. The aim of this study was to examine if restrictive red blood cell transfusion (RBC-T) practice for obstetric patients was in line with national Danish guidelines. METHODS: A retrospective quality assurance study was conducted at Rigshospitalet, Denmark. The study counted the participation of the Department of Anaesthesiology and Surgery, the Juliane Marie Centre, the Danish Blood Bank and the Department of Obstetrics. Patients were identified via the patient database of the Danish Blood Bank in 2015-2017, and patient files were read. RESULTS: Out of 16,698 delivering women, 196 (1.2%) received one or more RBC-T from 2015 to 2017. A total of 133 women (67.9%) received more than one RBC-T and the median was two. The most common reason for RBC-T was a "low haemoglobin level (Hb) + anaemic symptoms" (37.0%). A total of 20.3% of all RBC-Ts were prescribed based simply on a low Hb. The most common symptom of anaemia was dizziness. CONCLUSIONS: The majority of RBC-Ts for obstetric patients were conducted in line with the guidelines. However, 6.0% of RBC-Ts were registered to be in discrepancy with the guidelines and 20.3% of RBC-Ts were prescribed on the "low Hb" criterium solely. It is possible, though, that the 20.3% is overestimated due to insufficient descriptions of indications for RBC-T in patient files. FUNDING: none. TRIAL REGISTRATION: The study was approved by the management at Rigshospitalet.

Reducing the red blood cell transfusion threshold from 8·0 g/dl to 7·0 g/dl in acute myeloid leukaemia patients undergoing induction chemotherapy reduces transfusion rates without adversely affecting patient outcome.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) transfusions are needed by almost every acute myeloid leukaemia (AML) patient undergoing induction chemotherapy and constitute a cornerstone in supportive measures for cancer patients in general. Randomized controlled trials have shown non-inferiority or even superiority of restrictive transfusion guidelines over liberal transfusion guidelines in specific clinical situations outside of medical oncology. In this study, we analysed whether more restrictive RBC transfusion reduces blood use without affecting hard outcomes. MATERIALS AND METHODS: A total of 352 AML patients diagnosed between 2007 and 2018 and undergoing intensive induction chemotherapy were included in this retrospective analysis. In the less restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 8 g/dl (2007-2014). In the restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 7 g/dl (2016-2018). Liberal transfusion triggers were never endorsed. RESULTS: A total of 268 (76·1%) and 84 (23·9%) AML patients fell into the less restrictive and restrictive transfusion groups, respectively. The less restrictive transfusion group had 1 g/dl higher mean haemoglobin levels, received their first RBC transfusions earlier and needed 1·5 more units of RBC during the hospital stay of induction chemotherapy. Febrile episodes, C-reactive protein levels, admission to the intensive care unit, length of hospital stay as well as response and survival rates did not differ between the two cohorts. CONCLUSION: From our retrospective analysis, we conclude that a more restrictive transfusion trigger does not affect important outcomes of AML patients. The opportunity to test possible effects of the more severe anaemia in the restrictive transfusion group on quality of life was missed.

Death by Decade: Establishing a Transfusion Ceiling for Futility in Massive Transfusion.

BACKGROUND: Age and massive transfusion are predictors of mortality after trauma. We hypothesized that increasing age and high-volume transfusion would result in progressively elevated mortality rates and that a transfusion "ceiling" would define futility. METHODS: The Trauma Quality Improvement Program (TQIP) database was queried for 2013-2016 records and our level I trauma registry was reviewed from 2013 to 2018. Demographic, mortality, and blood transfusion data were collected. Patients were grouped by decade of life and by packed red blood cell (pRBC) transfusion requirement (zero units, 1-3 units, or ≥4 units) within 4 h of admission. RESULTS: TQIP analysis demonstrated an in-hospital mortality risk that increased linearly with age, to an odds ratio of 10.1 in ≥80 y old (P < 0.01). Mortality rates were significantly higher in older adults (P < 0.01) and those with more pRBCs transfused. In massively transfused patients, the transfusion "ceiling" was dependent on age. Owing to the lack granularity in the TQIP database, 230 patients from our institution who received ≥4 units of pRBCs within 4 h of admission were reviewed. On arrival, younger patients had significantly higher heart rates and more severe derangements in lactate levels, base deficits, and pH compared with older patients. There were no differences among age groups in injury severity score, systolic blood pressure, or mortality. CONCLUSIONS: In massively transfused patients, mortality increased with age. However, a significant proportion of older adults were successfully resuscitated. Therefore, age alone should not be considered a contraindication to high-volume transfusion. Traditional physiologic and laboratory criteria indicative of hemorrhagic shock may have reduced reliability with increasing age, and thus providers must have a heightened suspicion for hemorrhage in the elderly. Early transfusion requirements can be combined with age to establish prognosis to define futility to help counsel families regarding mortality after traumatic injury.

Audit of red blood cell transfusion in patients with acute leukemia at a tertiary care university hospital.

BACKGROUND: Red blood cell (RBC) transfusion support is essential in patients with acute leukemia (AL). A restrictive RBC transfusion approach is assumed to be safe for most individuals with AL. The aim of this audit was to assess RBC transfusion appropriateness in AL patients at an academic center. STUDY DESIGN AND METHODS: RBC transfusions in acute lymphoblastic leukemia and acute myeloid leukemia patients of all ages between January 1, 2013, and March 31, 2019, were analyzed for adherence to evidence-based criteria. Transfusion appropriateness was compared among ordering specialties, patient locations, and hematologic diagnoses. Pretransfusion hemoglobin was compared between categories. Overtransfusion rates were also analyzed. Descriptive statistics and categorical and numerical tests were employed to determine statistical significance. RESULTS: A total of 510 RBC transfusions were received by 133 AL patients in the departments of internal medicine, hematology, and pediatrics. Overall, 84.5% were appropriate according to established criteria. Internal medicine was the ordering department with the highest rate of appropriateness (88.1%). The outpatient clinic was the location with the highest adherence (85.9%), whereas the intensive care unit had the lowest (70%; p = 0.03). The reasons for most appropriate and inappropriate transfusions were asymptomatic anemia with a hemoglobin below (60.6%) or above (69.6%) 7 g/dL in patients without cardiac disease, respectively. Overtransfusion was present in 22% of episodes. CONCLUSION: RBC transfusion in AL patients reflected good adherence to guidelines. However, continuing education in transfusion medicine and prospective chart auditing are needed to improve adherence to established guidelines.