Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023.

Importance: Red blood cell (RBC) transfusions are frequently administered to preterm infants born before 32 weeks of gestation in the neonatal intensive care unit (NICU). Two randomized clinical trials (Effects of Transfusion Thresholds on Neurocognitive Outcomes of Extremely Low-Birth-Weight Infants [ETTNO] and Transfusion of Prematures [TOP]) found that liberal RBC transfusion thresholds are nonsuperior to restrictive thresholds, but the extent to which these results have been integrated into clinical practice since publication in 2020 is unknown. Objective: To describe neonatal RBC transfusion practice in Europe. Design, Setting, and Participants: This international prospective observational cohort study collected data between September 1, 2022, and August 31, 2023, with a 6-week observation period per center, from 64 NICUs in 22 European countries. Participants included 1143 preterm infants born before 32 weeks of gestation. Exposure: Admission to the NICU. Main Outcomes and Measures: Study outcome measures included RBC transfusion prevalence rates, cumulative incidence, indications, pretransfusion hemoglobin (Hb) levels, volumes, and transfusion rates, Hb increment, and adverse effects of RBC transfusion. Results: A total of 1143 preterm infants were included (641 male [56.1%]; median gestational age at birth, 28 weeks plus 2 days [IQR, 26 weeks plus 2 days to 30 weeks plus 2 days]; median birth weight, 1030 [IQR, 780-1350] g), of whom 396 received 1 or more RBC transfusions, totaling 903 transfusions. Overall RBC transfusion prevalence rate during postnatal days 1 to 28 was 3.4 transfusion days per 100 admission days, with considerable variation across countries, only partly explained by patient mix. By day 28, 36.5% (95% CI, 31.6%-41.5%) of infants had received at least 1 transfusion. Most transfusions were given based on a defined Hb threshold (748 [82.8%]). Hemoglobin levels before transfusions indicated for threshold were below the restrictive thresholds set by ETTNO in 324 of 729 transfusions (44.4%) and TOP in 265 of 729 (36.4%). Conversely, they were between restrictive and liberal thresholds in 352 (48.3%) and 409 (56.1%) transfusions, respectively, and above liberal thresholds in 53 (7.3%) and 55 (7.5%) transfusions, respectively. Most transfusions given based on threshold had volumes of 15 mL/kg (470 of 738 [63.7%]) and were administered over 3 hours (400 of 738 [54.2%]), but there was substantial variation in dose and duration. Conclusions and Relevance: In this cohort study of very preterm infants, most transfusions indicated for threshold were given for pretransfusion Hb levels above restrictive transfusion thresholds evaluated in recent trials. These results underline the need to optimize practices and for implementation research to support uptake of evidence.

Safe to save blood in ovarian cancer surgery - time to change transfusion habits.

BACKGROUND: Patients with advanced ovarian cancer (AOC) undergoing surgery are often subjected to red blood cell (RBC) transfusions. Both anemia and RBC transfusion are associated with increased morbidity. The aim was to evaluate patient recovery after the implementation of patient blood management (PBM) strategies. METHODS: This retrospective cohort study included 354 patients with AOC undergoing surgery at Skane University Hospital Lund, Sweden, between January 2016 and December 2021. The gradual implementation of PBM strategies included restrictive RBC transfusion, tranexamic acid as standard medication before laparotomies and intravenous iron administered to patients with iron deficiency. Severe complications were defined as Clavien-Dindo (CD) grade ≥ 3a. Logistic and linear regression analyses were used to evaluate the differences between three consecutive periods. RESULTS: After the implementation of new strategies, 52% of the patients had at least one transfusion compared to 83% at baseline (p < 0.001). There was no difference in the rate of severe complications (CD ≥ 3a) between the groups, adjusted odds ratio 0.55 (95% CI 0.26-1.17). The mean difference in hemoglobin before chemotherapy was -1.32 g/L (95% CI -3.04 to -0.22) when adjusted for blood loss and days from surgery to chemotherapy. The length of stay (LOS) decreased from 8.5 days to 7.5 days (p 0.002). INTERPRETATION: The number of patients transfused were reduced by 31%. Despite a slight increase in anemia rate, severe complications (CD ≥ 3a) remained stable. The LOS was reduced, and chemotherapy was given without delay, indicating that PBM is feasible and without causing major severe effects on short-term recovery.

A clinical audit of red blood cell transfusion practices at a district hospital in South Africa.

BACKGROUND:  Red blood cell (RBC) transfusion is one of the most critical and expensive lifesaving treatment modalities. A clinical audit is a valuable instrument to determine whether transfusion practices align with the guidelines and identify knowledge deficiencies. The study aimed to evaluate the RBC transfusion practices and patient outcomes at the National District Hospital in Bloemfontein, South Africa, and to determine adherence to transfusion guidelines. METHODS:  A retrospective descriptive study was conducted. All blood transfusion registers in the hospital were used to identify transfusion episodes during the study period. Files were retrieved from the admissions office and information captured on a paper-based datasheet. The appropriateness of the transfusion and adherence to the South African transfusion guidelines were evaluated using specific criteria. RESULTS:  Of the 118 transfusion episodes during the study period, 78 files were retrieved and 76 included in the study. The patients' median age was 47 years (interquartile range [IQR]: 32-66 years), with human immunodeficiency viruses (HIV) (n = 34; 44.7%) being the most common comorbid condition. Pre-transfusion haemoglobin was documented for all patients with a median of 4.6 g/dL (IQR: 3.95 g/dL - 5.5 g/dL). The audit revealed that in 68.4% (n = 52) of the cases, the guidelines were applied appropriately. CONCLUSION:  The study described the blood transfusion practices and identified shortcomings when compared with the standard clinical guidelines.Contribution: The study highlights the importance of applying rationale, caution and consideration of the specific patient profile when performing transfusions.

Huaxi integrated blood management reduces the red blood cell transfusion for on-pump cardiac surgery: A quasi-experimental study.

OBJECTIVE: As many as half of patients undergoing on-pump cardiac surgery require red blood cell transfusion, emphasizing the need for effective strategies that can reduce this need. We conducted this analysis to assess the effectiveness of Huaxi Integrated Blood Management strategy at our medical center. DESIGN: Before and after study. PARTICIPANTS: Patients who underwent on-pump cardiac surgery were included from January 2019 to December 2021. Two cohorts were compared, one before implementation of the strategy (1 January 2019 until 31 May 2020) and one after implementation (1 June 2020 until 31 December 2021). MEASUREMENTS: We evaluated temporal trends in blood transfusion, safety, and efficacy of this strategy. Primary outcomes were the incidence and volume of intra- and postoperative blood transfusions of packed red blood cells. Secondary outcomes are intraoperative and postoperative transfusion of other blood products, all-cause mortality during hospitalization, and incidence of new-onset complications. MAIN RESULTS: Our results demonstrated that this integrated strategy effectively decreased both the perioperative packed red blood cell transfusion volume and incidence for patients who underwent the on-pump cardiac surgery. Following the implementation, the incidence of packed red blood cell transfusions decreased by 8.1% during the intraoperative period and by 12.3% during the postoperative period. The mean volume of such transfusions decreased by 0.28 units during the intraoperative period and by 0.49 units during the postoperative period. Hemoglobin concentrations were significantly higher after implementation, and the maximal mean increase was 4.72 g/l on postoperative day 1. Similar benefit of the strategy was observed across subgroups of patients who underwent different types of surgery. CONCLUSIONS: The Huaxi Integrated Blood Management strategy may be effective at reducing the need for packed red blood cell transfusion and enhancing patient care.

Comprehensive perioperative blood management in patients undergoing elective bypass cardiac surgery: Benefit effect of health care education and systematic correction of iron deficiency and anemia on red blood cell transfusion.

STUDY OBJECTIVE: The aim of this study was to investigate the efficacy of a two-step patient blood management (PBM) program in red blood cell (RBC) transfusion requirements among patients undergoing elective cardiopulmonary bypass (CPB) surgery. DESIGN: Prospective, non-randomized, two-step protocol design. SETTING: Cardiac surgery department of Clinique Pasteur, Toulouse, France. PATIENTS: 897 patients undergoing for elective CPB surgery. INTERVENTIONS: We conducted a two-steps protocol: PBMe and PBMc. PBMe involved a short quality improvement program for health care workers, while PBMc introduced a systematic approach to pre- and postoperative correction of deficiencies, incorporating iron injections, oral vitamins, and erythropoiesis-stimulating agents. MEASUREMENTS: The PBM program's effectiveness was evaluated through comparison with a pre-PBM retrospective cohort after propensity score matching. The primary objective was the proportion of patients requiring RBC transfusions during their hospital stay. Secondary objectives were also analyzed. MAIN RESULTS: After matching, 343 patients were included in each group. Primary outcomes were observed in 35.7% (pre-PBM), 26.7% (PBMe), and 21.1% (PBMc) of patients, resulting in a significant reduction (40.6%) in the overall RBC transfusion rate. Both the PBMe and PBMc groups exhibited significantly lower risks of RBC transfusion compared to the pre-PBM group, with adjusted odds ratios of 0.59 [95% CI 0.44-0.79] and 0.44 [95% CI 0.32-0.60], respectively. Secondary endpoints included reductions in transfusions exceeding 2 units, total RBC units transfused, administration of allogeneic blood products, and total bleeding volume recorded on Day 1. There were no significant differences noted in mortality rates or the duration of hospital stays. CONCLUSIONS: This study suggests that health care education and systematic deficiency correction are associated with reduced RBC transfusion rates in elective CPB surgery. However, further randomized, controlled studies are needed to validate these findings and refine their clinical application.

Perioperative Transfusion Practices in Adults Having Noncardiac Surgery.

Surgical patients are often transfused to manage bleeding and anemia. Best practices for red blood cell (RBC) transfusion administration in patient having noncardiac surgery remains controversial and a robust evaluation and description of perioperative transfusion practices is lacking. We characterized perioperative hemoglobin concentrations and transfusion practices from the prospective VISION cohort which included 39,222 patients aged ≥45 years who had inpatient noncardiac surgery. Variations in transfusion practices were analyzed using hierarchical mixed models, and associations with mortality and complications were evaluated using a nested frailty survival model. Within the cohort, 16.1% (n = 6296) were given perioperative RBC transfusions, with the fraction declining from 20% to 13% over the 6-year study period. The proportion of patients transfused varied by surgery type from 6.4% for low-risk operations (i.e., minor surgery) to 31.5% for orthopedic surgeries. Variations were largely associated with patient hemoglobin concentrations, but also with center (range: 3.7%-27.3%) and country (0.4%-25.3%). Even after adjusting for baseline hemoglobin, comorbidities and type of surgery, both center and country were significant sources of variation in transfusion practices. Among transfused participants, 60.4% (n = 3728/6170) had at least 1 hemoglobin concentration ≤80g/L and 86.0% (n = 5305/6170) had at least 1 hemoglobin concentration ≤90g/L, suggesting that relatively restrictive transfusion strategies were used in most. The proportion of patients receiving at least 1 RBC transfusion declined from 20% to 13% over 6 years. However, there was considerable unexplained variation in transfusion practices.

Momelotinib versus Continued Ruxolitinib or Best Available Therapy in JAK Inhibitor-Experienced Patients with Myelofibrosis and Anemia: Subgroup Analysis of SIMPLIFY-2.

INTRODUCTION: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration. METHODS: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively. RESULTS: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower. CONCLUSION: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02101268.

Patients with the rare blood cancer myelofibrosis often experience symptoms such as tiredness, an increase in the size of their spleens (an organ involved in filtering the blood), and anemia (too few red blood cells). One type of treatment for myelofibrosis, called a Janus kinase (JAK) inhibitor, can help patients to feel better and reduce the size of their spleens, but some JAK inhibitors do not help with anemia and may make it worse. In those situations, patients may continue to take their JAK inhibitor but also receive another type of treatment, called an anemia supportive therapy, and may also receive red blood cell transfusions. This study compared 2 treatment approaches, continuing the JAK inhibitor ruxolitinib and adding an anemia supportive therapy and/or transfusions versus switching to another treatment called momelotinib, in 2 groups of patients from a clinical trial: (1) patients with levels of hemoglobin (a red blood cell protein) at the start of the trial that indicated that they had anemia, and (2) patients who were already receiving red blood cell transfusions at the start of the trial. In both groups, more patients did not need red blood cell transfusions anymore at week 24 with momelotinib, and their hemoglobin levels on average became higher over time. More patients also had improvements in spleen size and symptoms with momelotinib. Overall, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using supportive therapies and/or red blood cell transfusions to treat anemia.

Transfusion strategy trials excluding patients transfused outside the trial study period are more likely to report a trend favoring restrictive strategies: a meta-analysis.

OBJECTIVES: Some large, randomized trials investigating red cell transfusion strategies have significant numbers of transfusions administered outside the trial study period. We sought to investigate the potential impact of this methodological issue. STUDY DESIGN AND SETTING: Meta-analysis of randomized controlled trials (RCTs) comparing liberal vs restrictive transfusion strategies in cardiac surgery and acute myocardial infarction patients. The outcome of interest was 30-day or in-hospital mortality. RESULTS: In cardiac surgery, the pooled risk ratio for mortality was 0.83 (95% confidence interval [CI] 0.62-1.12, P = .22) times lower in the restrictive group when compared to the liberal group in trials applying a transfusion strategy throughout the patient's entire perioperative period, and 1.33 (95% CI 0.84-2.11, P = .22) times higher in the restrictive group in trials not applying transfusion strategies throughout the entire perioperative period. When combined, the risk ratio for mortality was 0.98 (95% CI 0.73-1.32, P = .89). In patients with acute myocardial infarction, the risk ratio for mortality was 0.72 (95% CI 0.40-1.28, P = .26) times lower in the restrictive group when compared to the liberal group in 1 trial excluding patients administered the intervention prerandomization and 1.19 (95% CI 0.96-1.47, P = .11) times higher in the restrictive group in 1 trial including patients receiving the intervention prerandomization. When combined the risk ratio for mortality was 1.00 (0.62-1.59, P = .99). CONCLUSION: Though not statistically significant, there was a consistent difference in trends between RCTs administering significant numbers of transfusion outside the trial study period compared to those that did not. The implications of our results may extend to RCTs in other settings that ignore if and how frequently an investigated therapy is administered outside the trial window.

Clinical burden and healthcare resource utilization associated with managing transfusion-dependent ß-thalassemia in France.

OBJECTIVE: To describe the clinical burden and healthcare resource utilization associated with managing transfusion-dependent ß-thalassemia (TDT) in France. METHODS: We used the French National Health Data System (système national des données de santé) to identify eligible patients from January 1, 2012, to March 1, 2019. Inclusion criteria were a diagnosis of ß-thalassemia, ≥8 red blood cell (RBC) transfusion episodes per year in ≥2 consecutive years following the diagnosis, and ≥1 year of follow-up data. Patients were excluded if medical records showed evidence of sickle cell disease, α-thalassemia, hereditary persistence of fetal hemoglobin, or hematopoietic stem cell transplant. Clinical complications, mortality, treatment use, and healthcare resource utilization were evaluated. RESULTS: Overall, 331 eligible patients with TDT were identified. Mean age was 26.1 (standard deviation [SD]: 18.0) years, and 50.5% were male. Common clinical complications were endocrine (26.0%), hepatobiliary (22.7%), and cardiopulmonary (18.7%). Fifteen (4.5%) patients died during follow-up, with a mortality rate of 1.16 deaths per 100 person-years (mean age of death: 52.5 years [SD: 22]). Patients had a mean of 13.5 (SD: 5.2) RBC transfusion episodes and 11.2 (SD: 5.3) iron chelation therapy treatments per year. Healthcare resource utilization was substantial, with a mean of 14.8 inpatient hospitalizations (including 13.8 mean inpatient day cases) and 16.9 outpatient prescriptions per patient per year. CONCLUSIONS: Patients with TDT in France experience significant clinical complications, elevated mortality, and substantial healthcare resource utilization driven by frequent RBC transfusion episodes and inpatient hospitalizations. These results reinforce the need for disease-modifying therapies for this patient population.

Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI.

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5-9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as "restrictive" or "liberal" based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5-9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7-8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70-0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15-3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07-2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76-1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59-6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022-11-07.

Reduction of red blood cell transfusion with a patient blood management protocol in urological and visceral surgery: a before-after study.

BACKGROUND: Although Patient Blood Management (PBM) is recommended by international guidelines, little evidence of its effectiveness exists in abdominal surgery. The aim of this study was to evaluate the benefits of the implementation of a PBM protocol on transfusion incidence and anaemia-related outcomes in major urological and visceral surgery. METHODS: In this before-after study, a three-pillar PBM protocol was implemented in 2020-2021 in a tertiary care centre, including preoperative correction of iron-deficiency anaemia, intraoperative tranexamic acid administration, and postoperative restrictive transfusion. A historical cohort (2019) was compared to a prospective cohort (2022) after the implementation of the PBM protocol. The primary outcome was the incidence of red blood cell transfusion intraoperatively or within 7 days after surgery. RESULTS: Data from 488 patients in the historical cohort were compared to 499 patients in the prospective cohort. Between 2019 and 2022, screening for iron deficiency increased from 13.9% to 69.8% (p < 0.01), tranexamic acid administration increased from 9.5% to 84.6% (p < 0.01), and median haemoglobin concentration before transfusion decreased from 77 g.L-1 to 71 g.L-1 (p = 0.02). The incidence of red blood cell transfusion decreased from 11.5% in 2019 to 6.6% in 2022 (relative risk 0.58, 95% CI 0.38-0.87, p = 0.01). The incidence of haemoglobin concentration lower than 100 g.L-1 at discharge was 24.2% in 2019 and 21.8% in 2022 (p = 0.41). The incidence of medical complications was comparable between the groups. CONCLUSION: The implementation of a PBM protocol over a two-year period was associated with a reduction of transfusion in major urological and visceral surgery.

Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support.

BACKGROUND: An estimated one-quarter to one-half of people diagnosed with haematological malignancies experience anaemia. There are different strategies for red blood cell (RBC) transfusions to treat anaemia. A restrictive transfusion strategy permits a lower haemoglobin (Hb) level whereas a liberal transfusion strategy aims to maintain a higher Hb. The most effective and safest strategy is unknown. OBJECTIVES: To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS: We searched for randomised controlled trials (RCTs) and non-randomised studies (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2023, Issue 2), and eight other databases (including three trial registries) to 21 March 2023. We also searched grey literature and contacted experts in transfusion for additional trials. There were no language, date or publication status restrictions. SELECTION CRITERIA: We included RCTs and prospective NRS that evaluated restrictive versus liberal RBC transfusion strategies in children or adults with malignant haematological disorders receiving intensive chemotherapy or radiotherapy, or both, with or without HSCT. DATA COLLECTION AND ANALYSIS: Two authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed the risk of bias. Any disagreement was discussed and resolved with a third review author. Dichotomous outcomes were presented as a risk ratio (RR) with a 95% confidence interval (CI). Narrative syntheses were used for heterogeneous outcome measures. Review Manager Web was used to meta-analyse the data. Main outcomes of interest included: all-cause mortality at 31 to 100 days, quality of life, number of participants with any bleeding, number of participants with clinically significant bleeding, serious infections, length of hospital admission (days) and hospital readmission at 0 to 3 months. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: Nine studies met eligibility; eight RCTs and one NRS. Six hundred and forty-four participants were included from six completed RCTs (n = 560) and one completed NRS (n = 84), with two ongoing RCTs consisting of 294 participants (260 adult and 34 paediatric) pending inclusion. Only one completed RCT included children receiving HSCT (n = 6); the other five RCTs only included adults: 239 with acute leukaemia receiving chemotherapy and 315 receiving HSCT (166 allogeneic and 149 autologous). The transfusion threshold ranged from 70 g/L to 80 g/L for restrictive and from 80 g/L to 120 g/L for liberal strategies. Effects were reported in the summary of findings tables only for the trials that included adults to reduce indirectness due to the limited evidence contributed by the prematurely terminated paediatric trial. Evidence from RCTs Overall, there may be little to no difference in the number of participants who die within 31 to 100 days using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 451 participants; RR 1.00, 95% CI 0.27 to 3.70, P=0.99; very low-certainty evidence). There may be little to no difference in quality of life at 0 to 3 months using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 431 participants; analysis unable to be completed due to heterogeneity; very low-certainty evidence). There may be little to no difference in the number of participants who suffer from any bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies; 448 participants; RR 0.91, 95% CI 0.78 to 1.06, P = 0.22; low-certainty evidence). There may be little to no difference in the number of participants who suffer from clinically significant bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (four studies; 511 participants; RR: 0.94, 95% CI 0.74 to 1.19, P = 0.60; low-certainty evidence). There may be little to no difference in the number of participants who experience serious infections at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies, 451 participants; RR: 1.20, 95% CI 0.93 to 1.55, P = 0.17; low-certainty evidence). A restrictive transfusion strategy likely results in little to no difference in the length of hospital admission at 0 to 3 months compared to a liberal strategy (two studies; 388 participants; analysis unable to be completed due to heterogeneity in reporting; moderate-certainty evidence). There may be little to no difference between hospital readmission using a restrictive transfusion strategy compared to a liberal transfusion strategy (one study, 299 participants; RR: 0.89, 95% CI 0.52 to 1.50; P = 0.65; low-certainty evidence). Evidence from NRS The evidence is very uncertain whether a restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-certainty evidence); or decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-certainty evidence). No NRS reported on the other eligible outcomes. AUTHORS' CONCLUSIONS: Findings from this review were based on seven studies and 644 participants. Definite conclusions are challenging given the relatively few included studies, low number of included participants, heterogeneity of intervention and outcome reporting, and overall certainty of evidence. To increase the certainty of the true effect of a restrictive RBC transfusion strategy on clinical outcomes, there is a need for rigorously designed and executed studies. The evidence is largely based on two populations: adults with acute leukaemia receiving intensive chemotherapy and adults with haematologic malignancy requiring HSCT. Despite the addition of 405 participants from three RCTs to the previous review's results, there is still insufficient evidence to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days, we would need a total of 1492 participants to have an 80% chance of detecting, at a 5% level of significance, an increase in all-cause mortality from 3% to 6%. Further RCTs are needed overall, particularly in children.

Discordance Rate and Risk Factor of Other Diagnostic Modalities for Small Bowel Tumors Detected by Device-Assisted Enteroscopy: A Korean Association for the Study of Intestinal Disease (KASID) Multicenter Study.

Background/Aims: Despite advances in imaging and endoscopic technology, diagnostic modalities for small bowel tumors are simultaneously performed. We investigated the discrepancy rate between each modality and predictive factors of discrepancy in patients with definite small bowel tumors. Methods: Data of patients with definite small bowel tumors who underwent both device-assisted enteroscopy (DAE) and computed tomography (CT) were retrieved from web-based enteroscopy registry database in Korea. Predictive risk factors associated with discrepancy were analyzed using logistic regression analysis. Results: Among 998 patients, 210 (21.0%) were diagnosed with small bowel tumor using DAE, in 193 patients with definite small bowel tumor, DAE and CT were performed. Of these patients, 12 (6.2%) showed discrepancy between examinations. Among 49 patients who underwent DAE and video capsule endoscopy (VCE) examination, 13 (26.5%) showed discrepancy between examinations. No significant independent risk factors were associated with concordance between DAE and CT in multivariate logistic regression analysis among the patients. In a multivariate logistic regression analysis, red blood cell transfusion was negatively associated with concordance between DAE and VCE in patients with small bowel tumor (odds ratio, 0.163; 95% confidence interval, 0.026 to 1.004; p=0.050). Conclusions: For small bowel tumors, the discrepancy rate between DAE and CT was 6.2%, and 26.5% between DAE and VCE. Despite developments in cross-sectional imaging (VCE and DAE modalities), discrepancies still exist. For small bowel bleeding that require significant transfusion while showing insignificant VCE findings, DAE should be considered as the next diagnostic approach, considering the possibility of missed small bowel tumor.

Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants. Objective: To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds. Design, Setting, and Participants: This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023. Exposures: First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group). Main Outcomes and Measures: The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk. Results: Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group. Conclusions and Relevance: The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01702805.

Four-factor prothrombin complex concentrate is not inferior to andexanet alfa for the reversal or oral factor Xa inhibitors: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC. METHODS: We performed a retrospective, noninferiority multicenter study of adult patients admitted from July 1, 2018, to December 31, 2019, who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with intensive care unit length of stay. MICE imputation was used to account for missing data and zero-inflated Poisson regression was used to account for an excess of zero units of RBC transfused. Two units difference in RBC transfusion was selected as noninferior. RESULTS: Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs. 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% confidence interval, 0.79-1.33) compared with AA after adjusting for other covariates. The average amount of RBC transfusion (nonzero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% confidence interval, 0.53-2.02) units compared with AA. CONCLUSION: PCC appears noninferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Peripheral perfusion index stratifies risk in patients with intraoperative anemia: A multicentre cohort study.

STUDY OBJECTIVE: Evidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality. DESIGN: Multicenter cohort study. SETTING: Bispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark. PATIENTS: We included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery. INTERVENTIONS: No interventions were carried out. MEASUREMENTS: Principal values collected included measurements of peripheral perfusion index and hemoglobin values. METHODS: The study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days. MAIN RESULTS: We included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231). Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62-5.45]) and 90-day mortality (3.13, [1.45-7.11]). A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57-162.10]). CONCLUSION: High PPI in acute surgical patients who also presents with anemia was associated with a significantly better outcome when compared with patients with both low PPI and anemia. PPI should therefore be further investigated as a potential parameter to guide intraoperative RBC transfusion therapy.

Process Mining Uncovers Actionable Patterns of Red Blood Cell Unit Wastage in a Health Care Network.

Packed red blood cell transfusions are integral to the care of the critically and chronically ill patient, but require careful storage and a large, coordinated network to ensure their integrity during distribution and administration. Auditing a Transfusion Medicine service can be challenging due to the complexity of this network. Process mining is an analytical technique that allows for the identification of high-efficiency pathways through a network, as well as areas of challenge for targeted innovation. Here, we detail a case study of an efficiency audit of the Transfusion Medicine service of the Nova Scotia Health Administration Central Zone using process mining, across a period encompassing years prior to, during, and after the acute COVID-19 pandemic. Service efficiency from a product wastage perspective was consistently demonstrated at benchmarks near globally published optima. Furthermore, we detail key areas of continued challenge in product wastage, and suggest potential strategies for further targeted optimization.

A survey on perioperative red blood cell transfusion trigger strategies for pediatric patients in the Nordic countries.

BACKGROUND: Transfusion of red blood cells (RBC) to rapidly increase hemoglobin levels have been associated with increased risks and worse outcomes in critically ill children. The international TAXI consensus from 2018 (pediatric critical care transfusion and anemia expertise initiative) recommended restrictive RBC transfusion strategies in pediatric patients. OBJECTIVE: To elucidate physicians perioperative RBC transfusion trigger strategies for pediatric patients in the Nordic countries and to investigate what factors influence the decision to transfuse this group of patients. METHODS: An electronic web-based survey designed by the TransfUsion triggers in Pediatric perioperAtive Care (TUPAC) initiative including six different clinical scenarios was sent to anesthesiologist treating pediatric patients at university hospitals in the Nordic countries on February 1, 2023 and closed May 1, 2023. RESULTS: The study had a response rate of 67.7% (180 responders out of 266 contacted). Median hemoglobin thresholds triggering RBC transfusions were 7.0 [IQR, 7.0-7.3] g/dL in a stable young child (1-year-old), 7.0 [IQR, 7.0-7.0] g/dL in the stable older child (5-year-old), 8.5 [IQR, 8.0-9.0] g/dL in the older child with cardiac disease, 9.0 [IQR, 8.0-10.0] g/dL the older child with traumatic brain injury, 8.0 [IQR, 7.3-9.0] g/dL in stabilized older child with septic shock and 8.0 [IQR, 7.0-9.0] g/dL in the older child with active but non-life-threatening bleeding. Apart from specific hemoglobin level, RBC transfusions were mostly triggered by high lactate level (74.2%), increasing heart rate (68.0%), prolonged capillary refill time (48.3%), and lowered blood pressure (47.8%). No statistical difference was found between the Nordic countries, work experience, or enrollment in a pediatric anesthesia fellowship program regarding RBC transfusion strategies. CONCLUSIONS: Anesthesiologists in the Nordic countries report restrictive perioperative RBC transfusion strategies for children that are mostly in agreement with the international TAXI recommendations. However, RBC transfusions strategies were modified to be guided by more liberal trigger levels when pediatric patients presented with severe comorbidity such as severe sepsis, septic shock, and non-life-threatening bleeding.

Clinical and biological factors associated with red blood cell transfusion during severe postpartum haemorrhage - A single-center retrospective cohort study.

INTRODUCTION: Red blood cell (RBC) transfusions are of utmost importance in the management of severe post-partum haemorrhage. Although the recommendations for blood transfusion protocols are regularly issued, there are significant differences in management depending on the context and the medical teams involved. OBJECTIVE: To determine during the first 24 h, the clinical and biological factors associated with the decision for RBC transfusion during severe PPH (≥1000 mL) for vaginal and caesarean deliveries. STUDY DESIGN: Monocentric retrospective study conducted in a tertiary care university maternity unit (CHI-Creteil) including all parturients from November 23th 2018 to 31th December 2020 with severe PPH (≥1000 mL). RESULTS: Over the study period, we reported 7103 deliveries, out of which 682 were complicated by PPH (9.6 %) with 200 cases of PPH ≥1000 mL (2.8 %). In our study, 40 % of patients (80/200) required a RBC transfusion". After multivariate analysis, severe PPH caused by placental abruption, uterine rupture or placental implantation disorders (aOR = 3.48 IC95 [1.27-9.52], p < 0.001), estimated blood loss ≥1500 mL (aOR = 9.60 IC95 [3.69-24.95], p < 0. 001), invasive measures such as uterine balloon tamponade, arterial ligation and uterine packing (aOR = 4.15 IC95 [1.80-9.61], p < 0.001), pre-labor hemoglobin <10 g/dL (aOR =4.88 IC95 [1.57-15.15], p < 0.001) or abnormal biological results in the acute phase (including hemoglobin <7.0 g/dL and/or fibrinogen <2 g/L and/or platelets <100 G/L) (aOR =356 IC95 [1,05-12,10], p < 0.001) were significantly and independently associated with the decision to initiate RBC transfusions. CONCLUSIONS: In a monocentric retrospective study including 200 consecutive cases of severe PPH (≥1000 mL) we identified groups of clinical and biological factors directly accessible to clinicians, significantly and independently associated with RBC transfusion in the first 24 h of management.

Adjusting Current Hemoglobin Thresholds: A Way to Improve Outcome in Women Undergoing Major Surgery.

Background/Objective: In the perioperative setting, a suboptimal total hemoglobin (Hb) mass puts women and men at an unreasonable disadvantage. Anemia is an independent risk factor for transfusion, postoperative complications, and mortality. The Hb cut-off value for women was set at <12.0 g/dL by the World Health Organization (WHO) and has been rigorously debated for decades. The aim of this study was to elucidate the risk for postoperative complications in female patients with Hb levels < 12.0, 12.0-12.9, and ≥13.0 g/dL. Material and Methods: Single-center retrospective analysis of female patients undergoing major surgery. Results: In total, 6,516 patients ≥18 years of age had major surgery between 2018 and 2019 and 2,446 female patients were included in analysis. Mean age was 67.4 ± 16.6, 66.4 ± 15.6, and 64.5 ± 15.5 years in female patients with preoperative Hb levels <12.0, 12.0-12.9 and ≥13.0 g/dL, respectively. The transfusion rate of red blood cells (RBCs) was significantly higher in female patients with Hb <12.0 g/dL (53%) and with Hb 12.0-12.9 g/dL (31%) compared to female patients ≥13.0 g/dL (22%). Rates of pneumonia, acute kidney injury, and sepsis were significantly higher in patients with Hb <12.0 and 12.0-12.9 g/dL compared to patients with Hb ≥13.0 g/dL. Total length of hospital stay was significantly longer in female patients with Hb <12.0 g/dL than patients with Hb 12.0-12.9 g/dL and Hb ≥13.0 g/dL (10 days vs. 8 days). Conclusion: Taken together, our data show that Hb values below 12.9 g/dL are associated with increased probability of RBC transfusions and increased risk of postoperative complications. In addition, our results indicate that postoperative outcomes for women might be optimized by increasing cut-off values for anemia. The call to revise the anemia threshold for women by the WHO can no longer be disregarded.