Hemoglobin Threshold For Transfusion Research Articles

An international survey of patient blood management practices.

The Association for the Advancement of Blood and Biotherapies (AABB) conducted a global survey of patient blood management (PBM) practices. It determined changes in PBM practices since the last survey. A working group of AABB's PBM Subsection and AABB staff designed the survey using the Qualtrics™ platform. The survey collected data from January 1, 2021, through December 31, 2021, and data analysis was conducted. Responses were received from 274 facilities across five World Health Organization (WHO) regions, from which 205 (74.8%) were from North America (NA), and 25.2% (69/274) were from outside of NA or the rest of the world (RoW). Of all respondents, 46.0% (126/274) had a PBM program. NA at 50.2% (103/205) was significantly higher than RoW at 33.3% (23/69) (p = .0049). In NA AABB transfusion guidelines, 36.8% (179/486) were the most followed versus RoW, with the Ministry of Health at 23.2% (29/125). The hemoglobin transfusion threshold of ≤7.0 g/dL (inpatients and outpatients) and platelet transfusion threshold of 5000/μL -10,000/μL (prophylaxis for inpatients and outpatients) were most commonly followed. Areas of improvement since the last AABB 2013 survey included providing PBM training increased to 61.7% (103/167) from 36.5% (219/600) and evaluation of patients undergoing elective surgical procedures for factors predictive of anemia to 46.0% (125/272) from 28% (144/507). While gains have been made in certain areas of PBM, there remains room for improvement, as more than half of respondents did not have a PBM program.

Effect of four hemoglobin transfusion threshold strategies in patients with acute myocardial infarction and anemia: a target trial emulation using MINT trial data

Abstract Background The hemoglobin (Hgb) threshold at which red blood cell transfusion affords greatest benefit, without increasing transfusion-associated risks, is uncertain for patients with acute myocardial infarction (MI). The Myocardial Ischemia and Transfusion (MINT) trial recently showed a restrictive transfusion strategy (Hgb threshold <7-8g/dL) resulted in a 15% increased risk of 30-day all-cause death or recurrent MI (death/MI) compared with a liberal strategy (Hgb threshold <10g/dL) in 3,504 adults with acute MI and anemia. However, the transfusion effect at different Hgb thresholds remains uncertain. Purpose To better understand the gradient of effects from Hgb threshold transfusion triggers between 7g/dL and 10g/dL. We estimated the effects of four Hgb transfusion thresholds on 30-day death/MI and death in patients with acute MI and anemia. Methods We used data from the MINT trial and applied an innovative causal inference method, target trial emulation, to assess four Hgb thresholds. We emulated a hypothetical, 4-arm target trial of <10g/dL, <9g/dL, <8g/dL, and <7g/dL transfusion strategies in adults with acute MI and Hgb <10g/dL using a "cloning" procedure. The target trial protocol closely mirrored that of the MINT trial. We conducted a per-protocol analysis of the emulated target trial using censoring and inverse probability (IP) weighting; we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by fitting pooled logistic regression models with a time-dependent intercept for time free of the outcomes. We estimated IP weighted Kaplan-Meier cumulative incidence curves under each strategy for 30-day outcomes. Results Of the MINT trial participants, 3,492 (99.7%) met eligibility criteria for the hypothetical target trial of four transfusion strategies. The unadjusted rate of 30-day death/MI was lowest in the <10g/dL strategy and highest in the <9g/dL strategy, and the rate of transfusions decreased monotonically as Hgb thresholds decreased. Relative to the <10g/dL strategy, the estimated HRs (95% CI) from the IP weighted model of 30-day death/MI were 1.07 (0.77-1.50) for the <9g/dL strategy, 1.14 (0.84-1.55) for the <8g/dL strategy, and 1.44 (0.99-2.09) for the <7g/dL strategy (Figure). A log-linear estimate over strategy thresholds between 7-10g/dL estimated a 1.12 (95% CI 1.00-1.27) times greater average risk of death/MI and a 1.12 (95% CI 0.92, 1.37) times greater average risk of death over 30 days for each 1g/dL decrease in the Hgb threshold. The IP weighted cumulative incidence curves showed similar increase in risk of death/MI as transfusion thresholds decreased throughout 30 days post-randomization. Conclusions Relative to a <10g/dL transfusion strategy, we estimated a progressively greater risk of 30-day death/MI as transfusion Hgb thresholds decreased within the range of 7-10g/dL. Targeting a Hgb concentration of 10g/dL in patients with a recent acute MI may avoid serious risks associated with anemia.Hazard ratios for 30-day death/MI

Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury

Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population. To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury. Multicenter, phase 3, parallel-group, investigator-initiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023. Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period. The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization. Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, -10.0% [95% CI, -16.5% to -3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P = .002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97]). Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy. ClinicalTrials.gov Identifier: NCT02968654.

Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis

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. 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. 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. 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). 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. 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. 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. ClinicalTrials.gov Identifier: NCT01702805.

Haemoglobin thresholds for transfusion: how are we doing in the era of Choosing Wisely? A retrospective cohort study.

Clinical practice guidelines and the Choosing Wisely initiative launched in 2012 recommend a haemoglobin (Hb) threshold of 70-80 g/lfor red blood cell (RBC) transfusions in stable hospitalised patients. Data on transfusion practices and their trends in medical inpatients are limited. To address this gap, we investigated transfusion practices and their trends in general internal medicine and other clinics. This retrospective cohort study analysed data from all hospitalisations with RBC transfusions at a Swiss university hospital between 2012 and 2019. We included all first transfusion episodes if pretransfusion Hb was available. The primary endpoint was mean pretransfusion Hb; secondary endpoints included potentially inadequate transfusions (i.e., transfusions at Hb ≥80 g/l) and receipt of a single RBC unit. Trends in mean pretransfusion Hb over time were estimated using generalised estimating equations, and risk factors for potentially inadequate transfusions were identified using multivariable adjusted generalised estimating equations models. Of 14,598 hospitalisations with RBC transfusions, 1980 (13.6%) were discharged from general internal medicine. From 2012 to 2019, mean pretransfusion Hb decreased from 74.0 g/l to 68.8 g/l in general internal medicine (mean annual decrease -0.76 g/l, 95% confidence interval [CI] -0.51 to -1.02) and from 78.2 g/l to 72.7 g/l in other clinics (mean annual decrease -0.69, 95% CI -0.62 to -0.77; p for interaction 0.53). The overall proportion of potentially inadequate transfusions was 17.8% in general internal medicine and 24.1% in other clinics (p <0.001) and decreased over the study period from 26.9% to 5.5% in general internal medicine and from 37.0% to 15.2% in other clinics. In contrast, the proportion of cases receiving a single RBC unit increased (39.5% to 81.4% in general internal medicine, 42.7% to 66.1% in other clinics). Older age (adjusted odds ratio [aOR] 1.45, 95% CI 1.32-1.58 for ≥65 vs <65 years), having surgery (aOR 1.24, 95% CI 1.14-1.36), acute haemorrhage (aOR 1.16, 95% CI 1.02-1.33), chronic heart failure (aOR 1.17, 95% CI 1.04-1.32), ischaemic heart diseases (aOR 1.27, 95% CI 1.15-1.41), chronic pulmonary diseases (aOR 1.24, 95% CI 1.08-1.42), malignancy (aOR 1.11, 95% CI 1.01-1.21), and rheumatic disease (aOR 1.27, 95% CI 1.01-1.59) were risk factors for potentially inadequate transfusions. More restrictive transfusion practices were adopted in general internal medicine and other clinics over time, suggesting that guideline recommendations and the Choosing Wisely initiative may have been increasingly followed. Interventions to reduce potentially inadequate transfusions should target providers who care for older patients and those with surgery or chronic cardiac and pulmonary diseases.

Red Blood Cell Conservation and Use in the Cardiovascular Operating Rooms at Ben Taub General Hospital

A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries. This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019. The data involved a single community hospital. A total of 417 patients were included in the study. The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation. Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663). The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL.

Lessons learned from patient outcomes when lowering hemoglobin transfusion thresholds during COVID-19 blood shortages.

This study examines whether patient outcomes were affected when the hemoglobin (Hb) transfusion threshold was lowered by 1 g/dL during COVID-19-related blood shortages. Outcomes of lowered Hb thresholds (from <7 to <6 g/dL) were defined by 14-month intervals in 2 patient groups (prepandemic [January 2019-February 2020] and pandemic [April 2020-May 2021]). We evaluated patient admissions, pretransfusion (if transfused) or nadir admission (if not transfused) Hb levels between 5.0 and 8.0 g/dL, and total red blood cell (RBC) transfusions during admission (if transfused). Baseline variables and outcomes were selected from electronic health records. Primary COVID-19-related admissions were excluded. Regression analysis was conducted to determine outcomes. Those in the prepandemic group (1976) and pandemic group (1547) were transfused. Fewer RBCs (2186, vs 3337) were used in the prepandemic group than in the pandemic group, respectively. Those in the prepandemic group had significantly higher rates of hypertension and diabetes as well as more smokers. Significant differences were observed when comparing the number of procedures and incidence of sepsis between the patient groups. Similar patterns were observed for the not transfused and transfused subgroups. Patient outcomes were not affected after implementing lower Hb pretransfusion thresholds. Although confounding factors were mitigated, some may have been associated with procedures or sepsis. Proactive patient blood management strategies during COVID-19-related blood shortages may include adopting lower Hb thresholds.

Hemoglobin modulation affects physiology and patient reported outcomes in anemic and non-anemic subjects: An umbrella review.

Background: An abnormal hemoglobin concentration has a substantial effect on a person's quality of life and physiology. Lack of tools that effectively evaluate hemoglobin-related outcomes leads to uncertainty regarding optimal hemoglobin levels, transfusion thresholds and treatment targets. We therefore aim to summarize reviews that assess the effects of hemoglobin modulation on the human physiology at various baseline hemoglobin levels, and identify gaps in existing evidence. Methods: We conducted an umbrella review of systematic reviews. PubMed, MEDLINE (OVID), Embase, Web of Science, Cochrane Library and Emcare were searched from inception to the 15th of April 2022 for studies that reported on physiological and patient reported outcomes following a hemoglobin change. Results: Thirty-three reviews were included of which 7 were scored as of high quality and 24 of critically low quality using the AMSTAR-2 tool. The reported data generally show that an increase in hemoglobin leads to improvement of patient reported and physical outcomes in anaemic and non-anaemic subjects. At lower hemoglobin levels, the effect of a hemoglobin modulation on quality of life measures appears more pronounced. Conclusion: This overview has revealed many knowledge gaps due to a lack of high-quality evidence. For chronic kidney disease patients, a clinically relevant benefit of increasing the hemoglobin levels up until 12g/dL was found. However, a personalized approach remains necessary due to the many patient-specific factors that affect outcomes. We strongly encourage future trials to incorporate physiological outcomes as objective parameters together with subjective, but still very important, patient reported outcome measures.

BLOOD TRANSFUSION IN THE EMERGENCY ROOM: EXPERIENCE OF IBN TOFAIL HOSPITAL IN MARRAKECH

Blood transfusion is frequently performed in intensive care. We carried out a prospective study with the objective of evaluating transfusion practices in the emergency room, transfusion thresholds, mortality, prognostic factors and transfusion deviations of labile blood products (LBP) compared to the recommendations of learned societies.This prospective survey was conducted in the vital emergency department of the Ibn Tofail hospital in Marrakech over a period of 6 months, and made it possible to collect data from 50 patients transfused in the emergency room. The mean age was 38±17 years. Patients with no particular pathological history accounted for 10% of cases. The mean SOFA score was 6.34 and the mean APACHE II score was 19.5. Indications for blood transfusion were dominated by hemodynamic instability (71.9%), acute hemorrhage (23.1%) and clinical intolerance of anemia (3.8%). Packed red blood cells (GC) were the most transfused blood product (76.9% of the total amount of transfused LBPs) followed by fresh frozen plasma (FFP) (8.1%) and platelet packs (CP) (1. 3%). The average consumption of CG was 2.3 ± 0.7 units per patient. His transfusion threshold responded to a restrictive strategy. The prescriptions complied with the recommendations of the Afsaps. The average consumption of PFC was 5.27±1.22 units per patient. Five transfusion episodes were deemed inappropriate. CPs were only transfused in 9 study patients. The average consumption was 4.4± 1.3 CP per patient. A single transfusion discrepancy was observed in a single patient. The mean hospital stay was 4±2.5 days. The mean hemoglobin transfusion threshold was 8.3±1.6 g/dl versus 10.3±1.6 g/dl post-transfusion.The mortality rate in the study was 36.9%. Transfusion was not a risk factor for mortality. Six patients developed post-transfusion accidents. Hyperthermia, the initial severity of the disease (high APACHE II and SOFA scores), coagulopathy and renal insufficiency were considered to be poor prognostic factors.

Multi‐national survey of transfusion experiences and preferences of patients with myelodysplastic syndrome

Transfusion dependence on red blood cells (RBCs) is common for patients with myelodysplastic syndromes (MDS) but transfusion practice and experience for outpatients with MDS are largely unknown. We conducted a web-based cross-sectional multi-national survey to audit real-world transfusion practices and understand the experiences and preferences of patients with MDS requiring RBC transfusion. The survey comprised 57 questions and was distributed to patients in the United States of America, Canada, and the United Kingdom. 447 respondents (45% female) with a median age of 72 years (IQR 66-77) were eligible on the basis of receiving an RBC transfusion in the last 8 weeks. There was wide variability in the hemoglobin thresholds for transfusion with the most common being <80 g/L. 40% of patients were transfused at a lower threshold (<70-75 g/L), with the largest proportion of these patients from the United States. Patients experienced significant symptoms prior to receiving a transfusion with fatigue and dyspnea having the most negative impacts on quality of life. Finally, patients endorsed two potential alterations to transfusion care that could improve their quality of life, including self-administered point of care testing of hemoglobin and higher hemoglobin transfusion thresholds. Of these patients, 62% preferred a threshold of at least 85 g/L, and 20% preferred a threshold of at least 100 g/L. In summary, this multi-national survey of patients with MDS requiring RBC transfusions demonstrated substantial variation in patients' experiences and preferences that differed also by country, supporting the need for further comparative clinical trials of transfusion practice interventions.

Effect of Initial Anticoagulation Targets on Bleeding and Thrombotic Complications for Patients With Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation

ObjectiveTo evaluate the effect of anticoagulation targets and intensity on bleeding events, thrombotic events, and transfusion requirements in patients with acute respiratory distress syndrome (ARDS) receiving venovenous extracorporeal membrane oxygenation (ECMO) and continuous-infusion heparin.DesignA retrospective cohort study.SettingAt a single-center, large academic medical center.ParticipantsOne hundred thirty-six critically ill patients.InterventionsThe following three therapeutic targets were implemented over time and evaluated: (1) no protocol (September 2013-August 2016): no standardized anticoagulation protocol or transfusion thresholds; (2) <50 seconds (September 2016-January 2018): standardized activated partial thromboplastin time (aPTT) goal of <50 seconds, maximum heparin infusion rate of 1,200 units/h, transfusion threshold of hemoglobin (Hgb) <8 g/dL; and (3) 40-to-50 seconds (February 2018-December 2019): aPTT goal of 40-to-50 sec, no maximum heparin infusion rate, transfusion threshold of Hgb <7 g/dL.Measurements and Main ResultsContinuous variables were compared using the Kruskal-Wallis test, and categorical variables were compared using Fisher exact tests. The primary endpoint, an incidence of at least 1 bleeding event, was highest in the no-protocol group though not statistically different among groups (39.3% v 26.7% v 34%, p = 0.5). Thrombotic complications were similar. The median units of packed red blood cells transfused were highest in the no-protocol group (3 v 2 v 0.5, p < 0.001).ConclusionAnticoagulation protocols standardizing aPTT goals to <50 or 40-to-50 seconds may be a reasonable strategy for patients receiving venovenous ECMO for ARDS. More restrictive hemoglobin transfusion thresholds, in combination with lower aPTT targets, may be associated with a reduction in transfusion requirements.

Is a higher hemoglobin transfusion threshold better for extremely low birthweight infants?

Is a higher hemoglobin transfusion threshold better for extremely low birthweight infants?

Red Blood Cell Transfusion at a Hemoglobin Threshold of 7 g/dl in Critically Ill Patients: A Regression Discontinuity Study.

Rationale: In critically ill patients, a hemoglobin transfusion threshold of <7.0 g/dl compared with <10.0 g/dl improves organ dysfunction. However, it is unclear if transfusion at a hemoglobin of <7.0 g/dl is superior to no transfusion. Objectives: To compare degrees of organ dysfunction between transfusion and no transfusion at a hemoglobin threshold of <7.0 g/dl among critically ill patients using quasiexperimental regression discontinuity methods. Methods: We performed regression discontinuity analysis using hemoglobin measurements from patients admitted to intensive care units in three cohorts (Medical Information Mart for Intensive Care IV, eICU, and Premier Inc.), estimating the change in organ dysfunction (modified sequential organ failure assessment score) in the 24- to 72-hour window following each hemoglobin measurement. We compared hemoglobin concentrations just above and below 7.0 g/dl using a "fuzzy" discontinuity approach, based on the concept that measurement noise pseudorandomizes similar hemoglobin concentrations on either side of the transfusion threshold. Results: A total of 11,181, 13,664, and 167,142 patients were included in the Medical Information Mart for Intensive Care IV (MIMIC-IV), eICU, and Premier Inc. cohorts, respectively. Patient characteristics below the threshold did not differ from those above the threshold, except that crossing below the threshold resulted in a >20% absolute increase in transfusion rates in all three cohorts. Transfusion was associated with increases in hemoglobin concentration in the subsequent 24-72 hours (MIMIC-IV, 2.4 [95% confidence interval (CI), 1.1 to 3.6] g/dl; eICU, 0.7 [95% CI, 0.3 to 1.2] g/dl; Premier Inc., 1.9 [95% CI, 1.5 to 2.2] g/dl) but not with improvement in organ dysfunction (MIMIC-IV, 4.6 [95% CI, -1.2 to 10] points; eICU, 4.4 [95% CI, 0.9 to 7.8] points; Premier Inc., 1.1 [95% CI, -0.2 to 2.3] points) compared with no transfusion. Conclusions: Transfusion was not associated with improved organ dysfunction compared with no transfusion at a hemoglobin threshold of 7.0 g/dl, suggesting that evaluation of transfusion targets other than a hemoglobin threshold of 7.0 g/dl may be warranted.

Abstract 9115: Determining Optimal Hemoglobin Transfusion Threshold for Patients With Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Introduction: Multiple randomized controlled trials have found that a conservative approach to transfusing critically ill patients reduces mortality, with current guidelines recommending a hemoglobin (HgB) transfusion threshold of 7 g/dL. However, little work has examined whether this transfusion threshold reduces mortality in patients with severe traumatic brain injury (TBI). Here, we present a systematic review and meta-analysis of the literature. Methods: A systematic search was conducted on PubMed, Ovid, and Web of Science. Full-text articles were eligible if patients with TBI, defined as Glasgow Coma Score &lt;= 8, were divided into multiple groups with varying hemoglobin transfusion thresholds and reported any outcome of interest including mortality, number of packed red blood cell (PRBC) units transfused, length of stay in ICU, and length of stay in the hospital. Eight studies were eligible (n = 3663). We compared mortality rates at HgB transfusion thresholds of &lt; 7 g/dL, &lt; 8 g/dL, &lt; 9 g/dL, and &lt; 10 g/dL. Results: We found that traditionally ‘conservative’ approaches to anemia management (HgB &lt; 7 g/dL, &lt; 8 g/dL, and &lt; 9 g/dL) were associated with decreased mortality when compared to traditionally ‘liberal’ approaches (HgB &lt; 10 g/dL), with p &lt; 0.05. Results were robust across both frequentist and Bayesian analysis. As a surrogate for cost of care and use of hospital resources, the total number of PRBC units transfused to patients, length of stay in ICU, and length of stay in hospital were analyzed. We found that using a transfusion threshold &lt; 7 g/dL compared to &lt; 10 g/dL substantially decreased the number of PRBC units transfused. In three of five cohorts, the cohort with the lower HgB transfusion threshold or no transfusion had a significantly shorter length of stay in the ICU and in the hospital. The remaining two cohorts found no significant difference in the length of stays in ICU or hospital. Conclusion: This study demonstrates that conservative approaches to transfusions ( &lt; 7 g/dL, &lt; 8 g/dL, or &lt; 9 g/dL) significantly reduce mortality and the number of PRBC units transfused when compared to more liberal approaches ( &lt; 10 g/dL). Current evidence is unclear on the benefits of conservative approaches in reduction of ICU or hospital length of stay.

S657 Hemoglobin Transfusion Threshold of 6 g/dL for Acute Gastrointestinal Bleeding in the Setting of Blood Shortage Due to COVID-19 Pandemic in a Tertiary Community Hospital

Introduction: Gastrointestinal bleed (GIB) is a common emergency condition associated with high mortality and morbidity. Current international guidelines recommend a hemoglobin (Hgb) transfusion threshold of 7 g/dL in patients with GIB. There was an initial blood shortage due to COVID-19 pandemic which prompted the need to lower hemoglobin. Primary outcome: rate of death from any cause within the first 30 days. Secondary outcome: rate of 30-day readmission and in-hospital complications. Methods: Retrospective single-center, IRB approved cohort. All adults (≥ 18 years old) who were admitted for GIB requiring blood transfusion prior to COVID-19 (10/1/2019-12-31/2019) and during the blood shortage period (4/1/2019-6/30/2020) due to COVID-19. Results: A total of 20 patients were admitted for GIB whose Hgb transfusion threshold at 7 g/dL prior to COVID-19, as compared with 17 patients with Hgb transfusion threshold at 6 g/dL during COVID-19 blood shortage period. There was no statistical significance in all cause mortality within the first 30 days (P=0.61), or rate of readmission within 30 days (P=0.42) when comparing the examined time period prior to versus during the time period with blood shortage due to COVID-19 pandemic. Also, there was no statistical difference between the two time periods when comparing in-hospital complications as a result of acute GIB (sepsis (P=1), acute kidney injury (P=0.58), hypoxia (P=1), unstable angina (P=1), NSTEMI (P=0.72), STEMI (P=0.42)). Conclusion: The rate of all-cause mortality within 30 days, 30-days readmission, and in-hospital complications from acute GIB did not differ when the hemoglobin transfusion threshold was lowered to 6 g/dL as compared to international guideline recommendation of 7 g/dL. The study is limited by small sample size; however, it reflects the patient population from a community hospital. If another pandemic is to occur, there may be less concern when there is a need to lower the Hgb transfusion threshold in the setting of blood loss anemia. The study helps to raise stronger awareness for blood donation to avoid blood shortage in the setting of an emergency, a pandemic in our case.Table 1.: Comparison of Inpatient Outcomes of NVUGIB Patients.

Anemia in septic shock: which transfusion thresholds?

Anemia is a frequent condition in intensive care units (ICU), most especially in septic patients. The hemoglobin level is a major determinant of oxygen transport. Red blood cell transfusion represents the main therapeutic of anemia in the ICU, and the only one able to rapidly increase the hemoglobin level in critical care. Overall, about half of septic patients will require red blood cell transfusion in the ICU and after discharge. Interventional randomized studies have demonstrated the safety and possibly a benefit of restrictive transfusion strategies in the ICU. Hence national and international guidelines consistently recommend such restrictive transfusion strategy by using a hemoglobin transfusion threshold of 7 g/dL to maintain a hemoglobin level between 7 and 9 g/dL in critically ill patients including septic patients. However, septic shock exhibits several features likely to modulate the transfusion indications, including the high prevalence of cardiovascular and onco-hematological comorbid conditions, as well as the defining tissue dysoxia. Transfusion indications in septic shock should certainly be based on the current guidelines, but most importantly should urge a personalized decision-making process taking into account an individual assessment of expected benefits and risks of transfusion.

Use of a Hemoglobin Substitute (HBOC-201) to Treat Acute Anemia in a Leukemic Patient with Anti-Vel Antibodies

BackgroundThe Vel-negative blood type is a rare autosomal recessive trait, occurring in 1 in 4000 persons. It is extremely difficult to supply blood to patients with anti-Vel antibodies, and the situation is even more challenging for Vel-negative patients with leukemia who may have high transfusion needs. There are case reports of treatment with hemoglobin substitutes in Jehovah's Witnesses and surgical patients. To the best of our knowledge, we report the first use of a hemoglobin substitute, HBOC-1201 (HemoPure) to treat a patient with refractory acute myeloid leukemia (AML) and anti-Vel antibodies.Case ReportOur patient is a 67-year-old Caucasian man with a one-year history of acute myeloid leukemia, refractory to multiple hypomethylator- and chemotherapy-based regimens. History is also significant for coronary artery disease with type 2 NSTEMI due to severe anemia. He has experienced prolonged pancytopenia due to leukemia and chemotherapy and required blood transfusions approximately weekly. Anti-Vel antibodies make transfusion of compatible blood challenging, and we utilized a hemoglobin transfusion threshold of 5 g/dL. Working with the American Red Cross and the American Rare Donor Program (ARDP), we transfused 44 units of Vel-negative blood over a one-year period, depleting the available Vel-negative units in North America. He presented to the hospital with productive cough and dyspnea. Initial labs revealed acute on chronic anemia with hemoglobin 3.5 g/dL. CT of the chest revealed right lower lobe pneumonia. Given critical anemia in the setting of pneumonia and possible sepsis, the patient needed immediate blood transfusion. Compatible Vel-negative blood was not available in North America. While awaiting availability of international blood units through the Red Cross and ARDP, we considered the choices of 1) transfusing incompatible blood or 2) administering a blood substitute. Because individuals with anti-Vel antibodies may develop severe acute hemolytic transfusion reactions when transfused incompatible blood, we chose to treat with HBOC-1201 (Biopure Corporation, Cambridge, MA), a bovine hemoglobin polymer that lacks a red blood cell membrane and thus red cell antigens such as Vel. We obtained an emergency IND from the FDA and local IRB approval. Three 32-gram units of HBOC-1201 were successfully transfused, with hemoglobin rise from 3.5 to 4.5 g/dL. Common adverse effects associated with the use of acellular hemoglobin substitutes include increase in concentration of methemoglobin and vasopressor effects leading to elevated blood pressure, fluid overload, and myocardial infarction. Our patient was monitored closely and tolerated the transfusion without any apparent adverse events.ConclusionDuring a challenging clinical situation, we successfully treated severe acute anemia in a patient with refractory AML and anti-Vel antibodies, using the acellular bovine hemoglobin-based blood substitute HBOC-1201, when compatible blood was not available. The infusion was tolerated without complications. Hemoglobin substitutes may be considered as bridging treatments in critically anemic patients such as those with hematologic malignancies when red blood cell transfusion is not an option. DisclosuresNo relevant conflicts of interest to declare.

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

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. To develop consensus statements to guide PRBC transfusion practices in patients with cervical cancer receiving curative-intent RT with EBRT and brachytherapy. 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. The preplanned primary outcome of this study was to assess hemoglobin transfusion thresholds and targets for both EBRT and brachytherapy by expert consensus. 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. 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.

Hemoglobin Transfusion Thresholds Outcomes for Preterm Infants

Hemoglobin Transfusion Thresholds Outcomes for Preterm Infants

The effect of blood transfusion on outcomes among African children admitted to hospital with Plasmodium falciparum malaria: a prospective, multicentre observational study

Infection with Plasmodium falciparum leads to severe malaria and death in approximately 400 000 children each year in sub-Saharan Africa. Blood transfusion might benefit some patients with malaria but could potentially harm others. The aim of this study was to estimate the association between transfusion and death among children admitted to hospital with P falciparum malaria. In this prospective, multicentre observational study, we analysed admissions to six tertiary care hospitals in The Gambia, Malawi, Gabon, Kenya, and Ghana that participated in the Severe Malaria in African Children network. Patients were enrolled if they were younger than 180 months and had a Giemsa-stained thick blood smear that was positive for P falciparum. Blood transfusion (whole blood at a target volume of 20 mL per kg) was administered at the discretion of the responsible physicians who were aware of local and international transfusion guidelines. The primary endpoint was death associated with transfusion, which was estimated using models adjusted for site and disease severity. We also aimed to identify factors associated with the decision to transfuse. The exploratory objective was to estimate optimal haemoglobin transfusion thresholds using generalised additive models. Between Dec 19, 2000, and March 8, 2005, 26 106 patients were enrolled in the study, 25 893 of whom had their transfusion status recorded and were included in the primary analysis. 8513 (32·8%) patients received a blood transfusion. Patients were followed-up until discharge from hospital for a median of 2 days (IQR 1-4). 405 (4·8%) of 8513 patients who received a transfusion died compared with 689 (4·0%) of 17 380 patients who did not receive a transfusion. Transfusion was associated with decreased odds of death in site-adjusted analysis (odds ratio [OR] 0·82 [95% CI 0·71-0·94]) and after adjusting for the increased disease severity of patients who received a transfusion (0·50 [0·42-0·60]). Severe anaemia, elevated lactate concentration, respiratory distress, and parasite density were associated with greater odds of receiving a transfusion. Among all study participants, transfusion was associated with improved survival when the admission haemoglobin concentration was up to 77 g/L (95% CI 65-110). Among those with impaired consciousness (Blantyre Coma Score ≤4), transfusion was associated with improved survival at haemoglobin concentrations up to 105 g/L (95% CI 71-115). Among those with hyperlactataemia (blood lactate ≥5·0 mmol/L), transfusion was not significantly associated with harm at any haemoglobin concentration-ie, the OR of death comparing transfused versus not transfused was less than 1 at all haemoglobin concentrations (lower bound of the 95% CI for the haemoglobin concentration at which the OR of death equals 1: 90 g/L; no upper bound). Our findings suggest that whole blood transfusion was associated with improved survival among children hospitalised with P falciparum malaria. Among those with impaired consciousness or hyperlactataemia, transfusion was associated with improved survival at haemoglobin concentrations above the currently recommended transfusion threshold. These findings highlight the need to do randomised controlled trials to test higher transfusion thresholds among African children with severe malaria complicated by these factors. US National Institute of Allergy and Infectious Diseases.