Number Of Red Blood Cell Transfusions Research Articles

Effect of blood sampling management on reducing blood transfusions in very preterm infants.

Effect of blood sampling management on reducing blood transfusions in very preterm infants.

Erken Hemoglobin Değeri ve Kan Transfüzyon Sayısı Bronkopulmoner Displaziyi Öngörebilir Mi?

Background: Currently, no practical biomarker has been discovered for early recognition of the development of bronchopulmonary dysplasia(BPD). This study aimed to evaluate the predictive value of early complete blood count (CBC) indices along with red blood cell transfusion(RBCT) frequency for the development of moderate/severe BPD, and to identify a promising predictive risk model for BPD. Methods: In this cross-sectional study, one-hundred-sixty-two neonates born before the 32nd weeks of gestation were retrospectively. Predictive role of CBC parameters in the first three postnatal days(PD) and the number of RBCTs on weekly basis were evaluated by univariate/multivariate analysis as well as multivariate data mining processing. Results: Despite several factors affected BPD development in univariate analysis, gestational age, PD3 haemoglobin level and frequency of RBCT were found to be the independent predictors of BPD in multivariate analysis. The haemoglobin<155 g/L in the PD3 predicted moderate/severe BPD with 60% sensitivity and 88% specificity(AUC 0.80). Having received at least one RBCT during the first three postnatal weeks had AUC 0.81(sensitivity 0.91,and specificity 0.81). During hospitalisation, more than four RBCT predicted moderate/severe BPD with 0.83 sensitivity and 0.93 specificity(AUC0.96). A model including gestational age, PD3 haemoglobin value, and number of RBCT predicted BPD risk with 87% sensitivity and 86% precision using data mining methods. Conclusion: Results emphasise that even just one blood transfusion in the first weeks is an independent risk factor for BPD. Even though BPD is multifactorial, initial haemoglobin value and RBCT frequency may serve as non-invasive and practical parameters to estimate BPD development risk.

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study.

Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients. This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion. Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders. RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion.

Increased red blood cell alloimmunization rates in transfused aplastic anemia and myelofibrosis patients.

Red blood cell (RBC) alloimmunization (AI) is a well-known complication of RBC transfusions, which results in the formation of alloantibodies to non-self antigens on donor RBCs, putting patients at risk of transfusion-related complications. The rate of AI with RBC transfusions in the general hospitalized population is estimated to be 2%-3%. However, some patients who are deemed "transfusion-dependent" require regular transfusions of blood products due to persistently low cell counts, putting them at even greater risk of RBC AI and increased morbidity. However, few studies currently exist investigating RBC AI in some transfusion-dependent patient populations, e.g., aplastic anemia (AA) and myelofibrosis (MF). We conducted a 5-year retrospective review to investigate the prevalence of RBC AI, alloantibody incidence, and the number of RBC transfusions in AA and MF patients, who received RBC transfusions within our hospital system. During the study period, 64 AA and 93 MF patients received 1301 and 2766 RBC transfusions, respectively. Compared to the RBC AI rate in the generalized hospitalized patient population (1%-2%), patients with AA and MF had an increased rate of RBC AI incidence rate at 14.1% and 12.9%, respectively. Furthermore, patients with primary MF demonstrated an isolated increased RBC AI incidence rate of 13.3%. The most common alloantibodies produced were anti-E and anti-K. Within our institution, patients with AA and MF had increased incidence rates of RBC AI compared to the general hospitalized patient population and may benefit from an antigen-matched protocol to minimize AI-related complications.

Impact of Delayed Cord Clamping on Red Blood Cell Transfusion and Related Outcomes in Very Low Birth Weight Infants.

Delayed cord clamping (DCC) for 30 to 60 seconds after birth facilitates placental transfusion, increases blood volume, and decreases red blood cell (RBC) transfusion in preterm infants. Study objective was to determine (1) RBC transfusion burden over a 5-year period, (2) impact of DCC practice on RBC transfusions, and (3) association of RBC transfusion on outcomes in very low birthweight (VLBW) preterm infants. A retrospective medical chart review was performed in 787 VLBW infants between 2016 and 2020. Demographic factors, DCC status, number of RBC transfusions, and neonatal outcomes were determined in eligible infants. Adjusted association between DCC, RBC transfusion, and outcomes were determined using logistic and linear regression methods. Of the 538 eligible VLBW infants, 62% (N = 332) received RBC transfusions. Proportion receiving RBC transfusion were significantly higher for infants <1,000 g (N = 217, 65.4%) and gestational age (GA) <29 weeks (N = 256, 77.1%) than larger (1,001-1,250 g, N = 77, 23.2% and 1,251-1,500 g, N = 38, 11.4%) and older GA ≥ 29 weeks' infants (N = 76, 22.9%, p < 0.05). Of the 81/538 (15.1%) who received DCC, 48 (59.2%) received no RBC transfusion (p < 0.001). In multivariable logistic regression analysis, preterm infants with DCC were 55% less likely to receive RBC transfusions as compared with infants with no DCC. At any given GA, the number of RBC transfusions in preterm infants with DCC was 25% lower as compared with infants without DCC (p < 0.05). Transfusion was associated with 8-fold increased odds for bronchopulmonary dysplasia and 4-fold increased odds for medical and surgically treated patent ductus arteriosus compared with no transfusion. There was no significant association of transfusion with neonatal sepsis, laser treated retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. DCC was significantly associated with reduced RBC transfusion, but fewer preterm infants received DCC. Further research is needed to explore the feasibility of providing neonatal resuscitation during DCC in preterm infants. · Delayed cord clamping significantly reduced the need for RBC transfusions.. · Fewer very preterm infants received DCC.. · Future research is needed to explore feasibility of neonatal resuscitation during DCC..

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

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

Paediatric clinical decision support: Evaluation of a best practice alert for red blood cell transfusion.

Providing red blood cell (RBC) transfusion to paediatric patients with a haemoglobin (Hb) level of <7 g/dL is the current best practice, but it is often difficult to ensure appropriateness of RBC transfusion on a health system level. Electronic health record (EHR) clinical decision support systems have been shown to be effective in encouraging providers to transfuse at appropriate Hb thresholds. We present our experience with an interruptive best practice alert (BPA) at a paediatric healthcare system. An interruptive BPA requiring physician response was implemented in our EHR (Epic Systems Corp., Verona, WI, USA) in 2018 based on Hb thresholds for inpatients. The threshold was initially <8 g/dL and later changed to <7 g/dL in 2019. We assessed total activations, number of RBC transfusions and hospital metrics through 2022 compared to the 2 years prior to implementation. The BPA activated 6956 times over 4 years, slightly less than 5/day, and the success rate, with no RBC transfusions within 24 h of order attempt, was 14.5% (1012/6956). There was a downward trend in the number of total RBC transfusions and RBC transfusions per admission after implementation, non-significant (p = 0.41 and p = >0.99). The annual case mix index was similar over the years evaluated. The estimated cost savings based on acquisition costs for RBC units were 213,822 USD or about $51,891 per year. BPA implementation led to sustained change in RBC transfusion towards best practice, and there were long-term savings in RBC expenditure.

Effectiveness of clinical decision support in controlling inappropriate red blood cell and platelet transfusions, speciality specific responses and behavioural change

BackgroundElectronic clinical decision support (CDS) within Electronic Health Records has been used to improve patient safety, including reducing unnecessary blood product transfusions. We assessed the effectiveness of CDS in controlling inappropriate red blood cell (RBC) and platelet transfusion in a large acute hospital and how speciality specific behaviours changed in response.MethodsWe used segmented linear regression of interrupted time series models to analyse the instantaneous and long term effect of introducing blood product electronic warnings to prescribers. We studied the impact on transfusions for patients in critical care (CC), haematology/oncology (HO) and elsewhere.ResultsIn non-CC or HO, there was significant and sustained decrease in the numbers of RBC transfusions after introduction of alerts. In CC the alerts reduced transfusions but this was not sustained, and in HO there was no impact on RBC transfusion. For platelet transfusions outside of CC and HO, the introduction of alerts stopped a rising trend of administration of platelets above recommended targets. In CC, alerts reduced platelet transfusions, but in HO alerts had little impact on clinician prescribing.ConclusionThe findings suggest that CDS can result in immediate change in user behaviour which is more obvious outside specialist settings of CC and HO. It is important that this is then sustained. In CC and HO, blood transfusion practices differ. CDS thus needs to take specific circumstances into account. In this case there are acceptable reasons to transfuse outside of these crude targets and CDS should take these into account.

Efficacy and Safety of Luspatercept in Adult Patients with Transfusion-Dependent Anemia Due to Very Low, Low and Intermediate Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts, Who Had an Unsatisfactory Response to or Are Ineligible for Erythropoietin-Based Therapy: A Retrospective Multicenter Study By Fondazione Italiana Sindromi Mielodisplastiche (FiSiM ETS)

Background: Patients with lower-risk myelodysplastic syndromes (MDS) who develop red blood cells (RBC) transfusion-dependent anemia, experience worse quality of life and shorter survival. Therapeutic strategies after failure of erythropoiesis stimulating agents (ESAs) are limited. Regulatory approval of luspatercept in lower-risk MDS with ring sideroblasts (MDS-RS) offers a novel approach for the treatment of transfusion-dependent anemia in this subset of patients. However, data about luspatercept effectiveness in a real-world clinical setting are lacking. Here we report the results of a multicenter retrospective study including patients who were treated with luspatercept within the Italian compassionate use program. Methods: Eligible patients were ≥ 18 years old, had MDS-RS (2016 WHO classification), met criteria for very low, low, or intermediate IPSS-R risk; were receiving regular RBC transfusions (≥2 units/8 weeks in the 16 weeks before study entry); were refractory to or unlikely to respond to ESAs. Primary end point was transfusion independence (TI) for 8 weeks or longer during weeks 1 through 24; key secondary end point was TI for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. Other secondary end points included erythroid response (defined by the IWG 2006 criteria), progression to acute myeloid leukemia (AML) and safety analyses. Exploratory analyses were performed to identify predictive factors for treatment response. Results: 184 patients who were enrolled in the Italian luspatercept compassionate use program between December 2020 and December 2021 were analyzed in this study. Median age at enrollment was 74 years (range, 31-88), median time since diagnosis was 43 months, and median time since onset of transfusion-dependence was 23 months. Overall, 123 (66.8%) patients had at least one comorbidity requiring ongoing treatment, 39 (21.2%) had at least three. Baseline median transfusion burden was 6 RBC units every 8 weeks (range, 2-25). At the time of data analysis (June 30, 2022), 130 (73.4%) patients completed at least 24 weeks of treatment. Median time on treatment was 301.5 days, and median follow-up time was 376 days. During the first 24 weeks of the trial, 59 (32%) patients had TI for 8 weeks or longer. The percentage of patients achieving TI increased to 38.6% in the first 48 weeks of the trial. Median duration of TI was 27.9 weeks. Focusing on secondary endpoints, 36 patients (19.6%) had TI for 12 weeks or longer during the first 24 weeks, 52 (28.3%) had TI for 12 weeks or longer considering the first 48 weeks of the trial. A reduction ≥ 4 RBC units/8 weeks during weeks 1-24 was seen in 66 patients (40.2%). Four (2.2%) patients evolved to AML. Serious adverse events were recorded in 27 (15.2%) patients and led to study discontinuation in 5 (2.8%). Overall, treatment was discontinued in 72 (40.7%) patients, mainly for lack of benefit (table 1) The maximum approved dose (1.75 mg/kg) of luspatercept was administered at least once in 144 (81%) patients. Among patients who achieved TI for 8 weeks or longer in the first 48 weeks, luspatercept dose (mg/kg) at response was 1, 1.33 and 1.75 in 31 (46.3%), 18 (29.9%) and 18 (29.9%%) patients, respectively. Logistic regression analysis showed that higher baseline transfusion burden was significantly associated with a lower probability of achieving TI. We identified 3 group of patients stratified according to baseline transfusion burden (group 1, ≤4 units/8 weeks; group 2, 5 to 7 units/8 weeks, group 3, ≥8 units/8 weeks) with a significantly different probability to achieve both the primary endpoint (51.9%, 35.2% and 16.7%, respectively, P<0.01) and the key secondary endpoint (30.8%, 24.1% and 9%, respectively, P<0.01). Patients with higher transfusion burden had higher luspatercept doses at first response (table 2). In patients with low probability to achieve TI (group 2 and 3), a reduction in transfusions equal or greater than 4 units/8 weeks was achieved in 66 (46.2%). Conclusion: Luspatercept was effective for the treatment of transfusion-dependent anemia in MDS-RS in a real-life setting. The benefit extended beyond the achievement of TI and produced a significant reduction in the number of RBC transfusions. Higher baseline transfusion burden was associated with a reduced probability to achieve TI; in these patients, the reduction of transfused RBC units appears a more reliable treatment target. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Ferric Carboxymaltose and Erythropoiesis-Stimulating Agent Treatment Reduces the Rate of Blood Transfusion in Refractory Anemia.

Background: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Guidelines suggest iron supplementation for unresponsive patients, regardless of iron deficiency. The primary aim of this study was to evaluate the effect of iron supplementation with ferric carboxymaltose (FCM) on the reduction of red blood cell transfusion (RBCT) rate in transfusion-dependent RA patients. Methods: This was a prospective quasi-randomized study, wherein patients were randomly assigned into three groups: (A) ESAs alone, (B) ferric gluconate (FG) and ESAs, and (C) FCM and ESAs. Hemoglobin and ferritin levels, as well as the number of RBCTs at 4 and 28 weeks were compared. Economic evaluation was also performed. Results: A total of 113 RA patients were enrolled. In total, 43 were treated with intravenous FG and ESAs, 38 with FCM and ESAs, and 32 with ESAs alone. At both follow-ups, erythropoietic response was increased in those receiving iron as compared with those with ESAs alone (p = 0.001), regardless of the type of iron. At one month, ferritin levels were higher in the FCM and ESA groups (p = 0.001). RBCTs were lower in both iron groups. The less costly treatment strategy was FCM, followed by FG, and lastly ESAs. Conclusions: Addition of iron to ESAs in RA reduced RBCT requirement and improved hemoglobin values.

Oral Roxadustat Demonstrates Efficacy in Anemia Secondary to Lower-Risk Myelodysplastic Syndrome Irrespective of Ring Sideroblasts and Baseline Erythropoietin Levels

Background: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. In Phase 3 trials, roxadustat increased hemoglobin (Hb) levels and reduced the number of red blood cell (RBC) transfusions vs placebo in patients with anemia of non-dialysis-dependent chronic kidney disease (CKD). In anemia of dialysis-dependent CKD, roxadustat achieved greater mean Hb increase vs epoetin alfa, and reduced IV iron use and RBC transfusions (Coyne, et al. Poster SA-0228 American Society of Nephrology (ASN) 2019; Charytan, et al. Poster SA-0227 ASN 2019) Low-risk myelodysplastic syndrome (LR-MDS), characterized by symptomatic anemia, is treated with RBC transfusion, erythropoiesis-stimulation agents (ESAs), or luspatercept. Suboptimal response and response durability across MDS subpopulations demonstrates an unmet medical need in LR-MDS. We report a 52-week update of the open-label (OL) phase of a study of roxadustat in anemia in primary MDS patients that determined the starting dose of the ongoing double-blind study phase (NCT03263091). Methods: The OL phase (N=24) used 3 sequential dose cohorts (1.5, 2.0, and 2.5 mg/kg) thrice weekly (TIW). Eligible patients had very low- to intermediate-risk primary MDS patients per International Prognostic Scoring System-Revised classification, with &amp;lt; 5% bone marrow blasts; baseline Hb &amp;lt; 10.0 g/dL; had low transfusion burden, defined as receiving 1-4 RBC units within 8 weeks before randomization; endogenous EPO levels ≤ 400 mIU/mL; and no 5q(del) cytogenetic abnormality. Red blood cell transfusion was allowed per institutional criteria. Roxadustat doses were titrated every 8 weeks based on Hb response and RBC transfusions. The primary endpoint was transfusion independence (TI) for ≥ 56 consecutive days during the first 28 treatment weeks; follow-up was at 52 weeks. Secondary endpoints included TI ≥ 56 consecutive days anytime during the study, proportion of patients who achieved ≥ 50% reduction in number of RBC transfusion over any 8 weeks vs baseline (BL), cumulative number of patient-exposure-week of TI, cumulative number of pRBC packs transfused, proportion of patients who achieved TI for &amp;gt; 20 weeks. Safety was assessed via adverse events monitoring and patients (%) who progressed to acute myeloid leukemia (AML). Patients with and without ring sideroblasts (RS+/RS-) and BL EPO ≤ 200 mIU/ml and &amp;gt; 200 mIU/ml were assessed for the primary endpoint. Results: In the OL phase, 24 transfusion-dependent LR-MDS patients were enrolled in 3 starting dose cohorts (Table). Nine patients (38%) achieved TI for ≥ 56 consecutive days within the first 28 and 52 weeks, 3 in cohort 1 (1.5 mg/kg), 1 in cohort 2 (2.0 mg/kg), and 5 in cohort 3 (2.5 mg/kg). When TI was achieved, 78% were receiving 2.5 mg/kg dose, 11% were receiving 2.0 mg/kg dose (started with 1.5 mg/kg) and 11% were receiving 1.5 mg/kg. Four patients (16.7%) remained TI for &amp;gt; 20 weeks (1 at 1.5 mg/kg dose level and 3 at 2.5 mg/kg dose-level) at 52 weeks. The 50% reduction in number of transfusion compared with BL occurred in 13 patients (54.2%) at 28 weeks and 14 (58.3%) at 52 weeks. In patients with TI duration ≥ 56 days (n = 9), the mean (SD) TI duration was 182.9 (153.66) days. In patients with TI duration ≥ 140 days (n = 4), the mean (SD) TI duration was 324.5 (121.22) days. Subgroups met the primary endpoint at week 28 (23.1% and 54.5% MDS-RS+ and -RS-, respectively, and 38.9% and 33.3% BL EPO ≤ 200 mIU/ml and &amp;gt; 200 mIU/ml, respectively); all subgroups maintained TI response to week 52. The overall safety profile was consistent with this patient population. Eight patients reported 8 treatment-emergent serious AEs; none were fatal. No patient progressed to AML. Conclusion: In this 52-week update, roxadustat 2.5 mg/kg TIW was effective in LR-MDS patients, based on observed response (TI and transfusion reduction), safety profile, and durable 52-week response. The ongoing, 156-patient, double-blind study phase uses a 2.5 mg/kg starting dose. Preliminary data in OL subgroups RS-/RS + and BL EPO ≤ 200 mIU/ml and &amp;gt;200 mIU/ml suggest roxadustat may be effective in these subgroups. These data await confirmation in the ongoing double-blind, placebo-controlled study. Table 1 Disclosures Carraway: Abbvie: Other: Independent Advisory Committe (IRC); ASTEX: Other: Independent Advisory Committe (IRC); Takeda: Other: Independent Advisory Committe (IRC); Stemline: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; BMS: Consultancy, Other: Research support, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Bradley:FibroGen, Inc.: Current Employment. Saha:FibroGen, Inc.: Current Employment. Bartels:FibroGen, Inc.: Current Employment. Leong:FibroGen Inc.: Current Employment, Current equity holder in private company. Yu:FibroGen, Inc.: Current Employment.

Late erythropoiesis-stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants.

Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia. Darbepoetin (Darbe) and EPO are currently available ESAs. To assess the effectiveness and safety of late initiation of ESAs, between eight and 28 days after birth, in reducing the use of red blood cell (RBC) transfusions in preterm or low birth weight infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 5 June 2018), Embase (1980 to 5 June 2018), and CINAHL (1982 to 5 June 2018). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised or quasi-randomised controlled trials of late initiation of EPO treatment (started at ≥ eight days of age) versus placebo or no intervention in preterm (< 37 weeks) or low birth weight (< 2500 grams) neonates. We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of the evidence. We include 31 studies (32 comparisons) randomising 1651 preterm infants. Literature searches in 2018 identified one new study for inclusion. No new on-going trials were identified and no studies used darbepoetin. Most included trials were of small sample size. The meta-analysis showed a significant effect on the use of one or more RBC transfusions (21 studies (n = 1202); typical risk ratio (RR) 0.72, 95% confidence interval (CI) 0.65 to 0.79; typical risk difference (RD) -0.17, 95% CI -0.22 to -0.12; typical number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 5 to 8). There was moderate heterogeneity for this outcome (RR I² = 66%; RD I² = 58%). The quality of the evidence was very low. We obtained similar results in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. There was no significant reduction in the total volume (mL/kg) of blood transfused per infant (typical mean difference (MD) -1.6 mL/kg, 95% CI -5.8 to 2.6); 5 studies, 197 infants). There was high heterogeneity for this outcome (I² = 92%). There was a significant reduction in the number of transfusions per infant (11 studies enrolling 817 infants; typical MD -0.22, 95% CI -0.38 to -0.06). There was high heterogeneity for this outcome (I² = 94%). Three studies including 404 infants reported on retinopathy of prematurity (ROP) (all stages or stage not reported), with a typical RR 1.27 (95% CI 0.99 to 1.64) and a typical RD of 0.09 (95% CI -0.00 to 0.18). There was high heterogeneity for this outcome for both RR (I² = 83%) and RD (I² = 82%). The quality of the evidence was very low.Three trials enrolling 442 infants reported on ROP (stage ≥ 3). The typical RR was 1.73 (95% CI 0.92 to 3.24) and the typical RD was 0.05 (95% CI -0.01 to 0.10). There was no heterogeneity for this outcome for RR (I² = 18%) but high heterogeneity for RD (I² = 79%). The quality of the evidence was very low.There were no significant differences in other clinical outcomes including mortality and necrotising enterocolitis. For the outcomes of mortality and necrotising enterocolitis, the quality of the evidence was moderate. Long-term neurodevelopmental outcomes were not reported. Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant (< 1 transfusion per infant) but not the total volume (mL/kg) of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes except for a trend in increased risk for ROP. Further research of the use of late EPO treatment, to prevent donor exposure, is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment. The use of satellite packs (dividing one unit of donor blood into many smaller aliquots) may reduce donor exposure.

44 Inhalation Injury Does Not Increase Blood Transfusion Requirements Following Burn Injury in Adults

Patients with major burns receive numerous red blood cell (RBC) transfusions for many indications, but it is not known whether an accompanying inhalation injury (INHI) influences the amount of blood transfused. The purpose of this study was to examine the effect of INHI on RBC transfusion in burned adults. This was a secondary analysis of a multi-center prospective randomized controlled trial that compared a liberal and restrictive blood transfusion threshold in adults with burns ≥ 20% TBSA. We compared 25 response variables between patients with and without INHI but here focus on the total number of RBC transfusions per patient (nRBC), the number of RBC transfusions per day (RBC/day), and the number of RBC transfusions/%TBSA burn (RBC/%). Generalized estimating equations (GEE) were used to account for clustering by facility. P values for response variable tests were adjusted for multiple comparisons. Multiple regression with GEE was used to identify variables that determined RBC/day. Values are shown as mean ± SD or median [25th,75th Q] as appropriate. Of 345 patients (age 42.9 +/- 16.8 years, %TBSA burn 38.0 +/- 17.6, 20.9% female, and admission APACHE 18.4 +/- 8.1) there were 78 (23%) with INHI. The table compares patients with and without INHI. The regression found that %TBSA burn (p<0.001), age (p=0.004), and requiring at least one day of mechanical ventilation(MV) (p < 0.0001) were significant determinants of RBC/day whereas INHI (p=0.251), and presence of at least one blood stream infection (p=0.107) were not. While patients with INHI tended to get more blood transfusions, this appears to have been determined by burn extent and requiring MV rather than the INHI itself. Presence of an INHI does not independently increase the need for RBC transfusions following a major burn injury. Table a P-values were not adjusted for multiple testing. Table a P-values were not adjusted for multiple testing.

No evidence that G6PD deficiency affects the efficacy or safety of daunorubicin in acute lymphoblastic leukemia induction therapy.

Anthracyclines are used in induction therapy of pediatric acute lymphoblastic leukemia (ALL) and are known to generate oxidative stress; whether this translates into enhanced antileukemic activity or hemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency is unknown. Among 726 pediatric patients with newly diagnosed ALL treated at St. Jude Children's Research Hospital, 22 had deficient G6PD activity. We compared the prevalence of positive minimal residual disease (MRD) ≥1% at Day 15/Day 19 of induction or ≥0.01% at Day 42/Day 46 (end of induction) and the number of red blood cell (RBC) transfusions after daunorubicin in induction between patients with or without G6PD deficiency, adjusting for ALL risk group, treatment protocol, age, and gender. There was no difference in Day 15/19 (P=1) or end of induction MRD (P=0.76) nor in the number of RBC transfusions (P=0.73); the lack of association with MRD was confirmed in a dataset of 1192 newly diagnosed male patients enrolled in a Children's Oncology Group trial (P=0.78). We found no evidence that G6PD deficiency affects daunorubicin activity during induction treatment for ALL.

Late erythropoiesis-stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants.

Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia. Darbepoetin (Darbe) and EPO are currently available ESAs. To assess the effectiveness and safety of late initiation of ESAs, between eight and 28 days after birth, in reducing the use of red blood cell (RBC) transfusions in preterm or low birth weight infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 5 June 2018), Embase (1980 to 5 June 2018), and CINAHL (1982 to 5 June 2018). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised or quasi-randomised controlled trials of late initiation of EPO treatment (started at ≥ eight days of age) versus placebo or no intervention in preterm (< 37 weeks) or low birth weight (< 2500 grams) neonates. We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of the evidence. We include 31 studies (32 comparisons) randomising 1651 preterm infants. Literature searches in 2018 identified one new study for inclusion. No new on-going trials were identified and no studies used darbepoetin.Most included trials were of small sample size. The meta-analysis showed a significant effect on the use of one or more RBC transfusions (21 studies (n = 1202); typical risk ratio (RR) 0.72, 95% confidence interval (CI) 0.65 to 0.79; typical risk difference (RD) -0.17, 95% CI -0.22 to -0.12; typical number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 5 to 8). There was moderate heterogeneity for this outcome (RR I² = 66%; RD I² = 58%). The quality of the evidence was very low. We obtained similar results in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. There was no significant reduction in the total volume (mL/kg) of blood transfused per infant (typical mean difference (MD) -1.6 mL/kg, 95% CI -5.8 to 2.6); 5 studies, 197 infants). There was high heterogeneity for this outcome (I² = 92%). There was a significant reduction in the number of transfusions per infant (11 studies enrolling 817 infants; typical MD -0.22, 95% CI -0.38 to -0.06). There was high heterogeneity for this outcome (I² = 94%).Three studies including 404 infants reported on retinopathy of prematurity (ROP) (all stages or stage not reported), with a typical RR 1.27 (95% CI 0.99 to 1.64) and a typical RD of 0.09 (95% CI -0.00 to 0.18). There was high heterogeneity for this outcome for both RR (I² = 83%) and RD (I² = 82%). The quality of the evidence was very low.Three trials enrolling 442 infants reported on ROP (stage ≥ 3). The typical RR was 1.73 (95% CI 0.92 to 3.24) and the typical RD was 0.05 (95% CI -0.01 to 0.10). There was no heterogeneity for this outcome for RR (I² = 18%) but high heterogeneity for RD (I² = 79%). The quality of the evidence was very low.There were no significant differences in other clinical outcomes including mortality and necrotising enterocolitis. For the outcomes of mortality and necrotising enterocolitis, the quality of the evidence was moderate. Long-term neurodevelopmental outcomes were not reported. Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant (< 1 transfusion per infant) but not the total volume (mL/kg) of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes except for a trend in increased risk for ROP. Further research of the use of late EPO treatment, to prevent donor exposure, is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment. The use of satellite packs (dividing one unit of donor blood into many smaller aliquots) may reduce donor exposure.

Impact of Real-Time Clinical Decision Support on Blood Utilization and Outcomes in Hospitalized Patients with Solid Tumor Cancer

Patients with cancer are frequently hospitalized, and anemia is a common complication of cancer care. Transfusion is often required and commonly occurs above guideline-supported thresholds. It was hypothesized that an educational intervention, combined with real-time clinical decision support (CDS), would reduce blood utilization among hospitalized solid tumor cancer patients without adversely affecting outcomes. A retrospective, historical control analysis was conducted comparing transfusion utilization among hospitalized solid tumor cancer patients before and after implementation of the educational intervention and CDS. The primary outcome was receipt of red blood cell (RBC) transfusion. Secondary outcomes included total RBC transfusions per 100 inpatient-days, readmission, outpatient transfusion within seven days of discharge, inpatient mortality, and odds of transfer to the ICU. The odds of receiving a transfusion were significantly reduced in the postintervention cohort (odds ratio [OR] = 0.52, p = 0.005). Among patients receiving transfusion, there was no significant difference between groups in the number of RBC transfusions per 100 inpatient-days (incidence rate ratio = 0.87, p = 0.26). There were also no significant differences in readmission, outpatient transfusion within seven days of discharge, or inpatient mortality, though patients in the postintervention cohort had lower odds of ICU transfer (OR = 0.29, p = 0.04). The combined use of an educational intervention and CDS in a hospitalized solid tumor cancer patient population was associated with lower blood utilization, similar patient outcomes, and unchanged short-term outpatient transfusion requirements. Hospitals should consider similar interventions to work toward appropriate resource allocation and mitigation of transfusion-associated risk in this patient population.

Postpartum blood transfusion and hemorrhage as independent risk factors for venous thromboembolism

IntroductionProfuse postpartum hemorrhage (PPH) and red blood cell (RBC) transfusion have been suggested to be associated with venous thromboembolic events (VTE). However, it is not fully clear if they are independent major risk factors. MethodsWomen who gave birth in the Stockholm area between 1999 and 2002 were those studied, i.e., before the implementation of guidelines for thromboprophylaxis in pregnancy. In this population-based cohort study the Swedish Medical Birth Registry was linked to the National Discharge Registry and to the transfusion database. Cases with VTE were identified as well as the patient's transfusion history. The main outcome was an assessment of RBC transfusion and PPH as independent risk factors for postpartum thrombosis, analyzed in logistic regression models. ResultsOut of the 82,376 deliveries, 56 cases of postpartum VTE were identified (0.7‰). Compared to the control group, the risk of VTE increased with the number of RBC transfusions: 1 to 3 units (OR = 3.3, 95% CI 1.2–8.9) and >3 units (OR = 5.2, 95%CI 1.7–16.1), but PPH was not found to be a major risk factor (OR = 1.4, 95% CI 0.5–3.5). Surprisingly, the small group treated with plasma in addition to RBC transfusion were not at a significantly increased risk (OR = 1.8, 95% CI 0.2–14.0). Preeclampsia and placental abruption were major risk factors. ConclusionWe found RBC transfusion, but not PPH alone, to be an independent risk factor for postpartum VTE and propose that it should be included in the thromboprophylaxis algorithm for implementation during pregnancy.

Ferric carboxymaltose with or without erythropoietin in anemic patients with hip fracture: a randomized clinical trial.

The increasing incidence of osteoporotic hip fracture (HF) has raised the requirements of red blood cell (RBC) transfusions, whereas this scarce resource may cause morbidity and mortality. This study was a multicenter, randomized, double-blind, clinical trial that aimed to assess efficacy of ferric carboxymaltose (FCM) with or without erythropoietin (EPO) in reducing RBC transfusion in the perioperative period of HF. Participants (patients > 65 years admitted with HF and hemoglobin [Hb] levels of 90-120 g/L) were randomly assigned to receive a preoperative single dose of 1 g of FCM (short intravenous [IV] infusion over 15 min), plus 40,000 IU of subcutaneous EPO (EPOFE arm); versus 1 g of IV FCM plus subcutaneous placebo (FE arm); and versus IV and subcutaneous placebo (placebo arm). Primary endpoint was the percentage of patients who received RBC transfusion, and secondary endpoints were the number of RBC transfusions per patient, survival, hemoglobinemia, and health-related quality of life (HRQoL; by means of Short Form 36 Version 2 questionnaire). A total of 306 patients (85% women, mean age 83 ± 6.5 years) were included. A total of 52, 51.5, and 54% of patients required RBC transfusion in the EPOFE, FE, and placebo arms, respectively, with no significant differences in the number of RBC transfusions per patient, survival, HRQoL, and adverse events among treatment groups. A significant increase in Hb levels was achieved at discharge (102 g/L vs. 97 g/L) and 60 days after discharge (125 g/L vs. 119 g/L) in the EPOFE arm with respect to placebo arm; in addition, a higher rate of patients recovered from anemia in the EPOFE arm with respect to the placebo arm (52% vs. 39%), 60 days after discharge. Preoperative treatment with FCM alone or in combination with EPO improved recovery from postoperative anemia, but did not reduce the needs of RBC transfusion in patients with HF.

Relationship between red blood cell transfusion requirements and severity of renal disease during the acute stage of hemolytic uremic syndrome.

We performed a retrospective evaluation of patients with diarrhea-associated hemolytic uremic syndrome (D + HUS) with the aims of: (1) determining the rate of red blood cell (RBC) transfusions; (2) establishing the relationship between need for RBC transfusion and severity of renal involvement; (3) determining whether precise measurements of lactic dehydrogenase (LDH) levels can predict the rate of hemolysis and severity of renal disease. A total of 288 patients with D + HUS were retrospectively divided into three groups based on dialysis treatment: group 1, no dialysis treatment (144 patients); group 2, dialysis for 1-10 days (67 patients); group 3, dialysis for ≥11 days (77 patients). Of the patients in groups 1, 2 and 3, 73.6, 86.5 and 83.1%, respectively, required at least one RBC transfusion. The number of RBC transfusions in groups 1, 2 and 3 was 163, 107 and 162, respectively. Comparison of the groups revealed that the number of RBC transfusions was significantly higher in patients in groups 2 and 3 than in those in group 1 (p = 0.0001). Most RBC transfusions (94.2%) occurred during the first 2 weeks of the disease. The median peak LDH level was 2091 U/l in 32 patients with no RBC transfusion (group A), 3900 U/l in 73 patients with one transfusion (group B) and 6378 U/l in 62 patients with two or more transfusions (group C). Patients who received two or more RBC transfusions had a significantly higher median peak LDH level than those who did not receive RBC transfusions or received only one transfusion. This difference was also observed between patients who received only one RBC transfusion and those who did not receive any transfusions (p < 0.00001). Comparison of LDH levels on admission and peak LDH levels among patients in groups A, B and C revealed that 28/32 patients in group A, 56/73 patients in group B and 33/62 patients in group C had a stable LDH level, suggesting that patients with a stable LDH level require fewer RBC transfusions (p ≤ 0.006). Finally, we evaluated the possibility of an association between peak LDH levels and the degree of renal disease. The median peak LDH level in patients of group 1, 2 and 3 was 3538 (range 756-9373), 5165 (451-9205) and 7510 (1,145-16,340) U/l, respectively. Patients with >10 days of dialysis (group 3) had the highest LDH levels, followed by patients with 1-10 days of dialysis (group 2) and then by patients with no dialysis requirements (group 1) (p < 0.00001). The rate of RBC transfusion was higher in patients with the most severe renal injury, and most were performed during the first 2 weeks of the disease. Patients with stable LDH levels seemed to require fewer RBC transfusions. Median peak LDH levels were significantly higher in the group of patients with the most severe renal disease.

The Impact of Perioperative Iron on the Use of Red Blood Cell Transfusions in Gastrointestinal Surgery: A Systematic Review and Meta-Analysis

Perioperative anemia is common, yet detrimental, in surgical patients. However, red blood cell transfusions (RBCTs) used to treat anemia are associated with significant postoperative risks and worse oncologic outcomes. Perioperative iron has been suggested to mitigate perioperative anemia. This meta-analysis examined the impact of perioperative iron compared to no intervention on the need for RBCT in gastrointestinal surgery. We systematically searched Medline, Embase, Web of Science, Cochrane Central, and Scopus to identify relevant randomized controlled trials (RCTs) and nonrandomized studies (NRSs). We excluded studies investigating autologous RBCT or erythropoietin. Two independent reviewers selected the studies, extracted data, and assessed the risk of bias using the Cochrane tool and Newcastle-Ottawa scale. Primary outcomes were proportion of patients getting allogeneic RBCT and number of transfused patient. Secondary outcomes were hemoglobin change, 30-day postoperative morbidity and mortality, length of stay, and oncologic outcomes. A meta-analysis using random effects models was performed. The review was registered in PROSPERO (CRD42013004805). From 883 citations, we included 2 RCTs and 2 NRSs (n = 325 patients), all pertaining to colorectal cancer surgery. Randomized controlled trials were at high risk for bias and underpowered. One RCT and 1 NRS using preoperative oral iron reported a decreased proportion of patients needing RBCT. One RCT on preoperative intravenous iron and 1 NRS on postoperative PO iron did not observe a difference. Only 1 study revealed a difference in number of transfused patients. One RCT reported significantly increased postintervention hemoglobin. Among 3 studies reporting length of stay, none observed a difference. Other secondary outcomes were not reported. Meta-analysis revealed a trend toward fewer patients requiring RBCT with iron supplementation (risk ratio, 0.66 [0.42, 1.02]), but no benefit on the number of RBCT per patient (weighted mean difference, -0.91 [-1.61, -0.18]). Although preliminary evidence suggests that it may be a promising strategy, there is insufficient evidence to support the routine use of perioperative iron to decrease the need for RBCT in colorectal cancer surgery. Well-designed RCTs focusing on the need for RBCT and including long-term outcomes are warranted.