Transfusion Of Red Blood Cell Units Research Articles

ASCENT1: A Phase 2 Trial to Evaluate the Efficacy and Safety of Oral Decitabine-Tetrahydrouridine (NDec) in Patients with Sickle Cell Disease

Background: Sickle cell disease (SCD) is driven by the polymerization of mutated hemoglobin (HbS) in red blood cells (RBCs). Fetal hemoglobin (HbF) mitigates the effects of HbS polymerization, but the HbF gene expression is silenced in infancy by DNA methyltransferase 1 (DNMT1). Decitabine induces HbF expression by direct inhibition of DNMT1. NDec is an innovative combination treatment with decitabine, the active component, and the pharmacokinetic enhancer tetrahydrouridine (THU). Hydroxyurea (HU), the current standard of SCD care, indirectly induces HbF by inducing bone marrow stress. As the indirect effect of HU on HbF is clinically variable, the direct HbF induction of NDec is hypothesized to provide a sustainable treatment option for patients with SCD. In a previous trial in high-risk patients with SCD by Molokie R et al. (2017), oral decitabine (0.16 mg/kg) and THU vs placebo significantly increased total Hb, HbF, proportion of HbF-enriched RBCs (%F-cells) and improved RBC health markers, without triggering grade ≥3 non-hematologic toxicity. NDec formulations were further investigated in 2 phase 1 trials in healthy people. The ASCENT1 trial (NCT05405114) aims to study the efficacy and safety of once- or twice-weekly NDec vs placebo in patients with SCD. This study will provide proof of concept and determine the optimal dose for future trials. Study design: ASCENT1 is a randomized, placebo-controlled phase 2 trial with an additional exploratory open-label HU block (Figure). To ease the operational aspects for patients and sites, trial design, visit schedule and trial materials were developed together with patient groups, study nurses and coordinators. The HU non-eligible block will include those who are HU-naïve or who cannot be treated with HU for any reason. Participants randomized to NDec in the HU active block will discontinue HU during a 4-week washout period. Study population: All SCD genotypes are eligible for inclusion; other criteria are ≥18 years of age, 2-10 documented vaso-occlusive crises (VOCs) ≤12 months before screening, Hb ≥5.0-≤10.5 g/dL and reticulocyte count >1.5x upper limit of normal at screening. HU active participants are eligible only if deemed inadequately controlled by investigators despite being prescribed HU in the preceding 6 months and being on a stable dose >3 months. Exclusion criteria include chronic transfusion therapy or treatment 28 days before screening/during trial with hematopoietic growth factors and treatment with voxelotor, crizanlizumab or L-glutamine 12 weeks before signing informed consent. Study treatment and endpoints: HU non-eligible (n=60) and HU active (n=24) participants will be randomized 1:1:1 to NDec once weekly, NDec twice weekly (2 consecutive days) or placebo/open-label HU. The trial consists of a main and extension phase (24 weeks each). NDec will be administered orally, with a meal, according to body weight intervals to attain a decitabine dose level of 0.16−0.25 mg/kg and THU dose level of 8−12.5 mg/kg. The primary endpoint is change in total Hb (g/dL) from baseline (BL) to Week 24. Secondary efficacy endpoints include change in HbF (g/dL and %HbF of total Hb), change in %F-cells of total RBCs, and change in hemolysis markers from BL to Week 24. Secondary efficacy endpoints also include numbers of VOCs, acute chest syndrome and transfused RBC units from BL to Week 48. The secondary safety endpoint is the number of adverse events (grade ≥3) from BL to Week 52. Changes in patient-reported outcomes from BL to Week 48 will be assessed using 5 validated questionnaires for SCD. Statistical analysis: The primary endpoint will be analyzed using an ANCOVA model with treatment, historical VOC rate and sex as fixed factors, and BL Hb as covariate. Treatment policy estimand will be used to handle intercurrent events. Considerations: In this trial, VOCs are defined as ≥1 predefined clinical events requiring a medical visit, including home and telemedicine visits, for those with limited regular access to medical management at a clinic/hospital. NDec and HU both induce HbF and will not be given together due to a theoretical potentiation of hematologic toxicity. The exploratory HU active block enables preliminary comparisons of the efficacy and safety between NDec and HU. The extension phase allows for analyses that may require longer follow-up to show clinical benefits and sustainability of NDec in SCD. The recruitment to ASCENT1 started in summer 2022. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Red Blood Cell Utilization Among Patients with Sickle Cell Disease: A Single Center Experience

Introduction: Red blood cell (RBC) transfusion remains a mainstay of treatment for both acute and chronic complications of sickle cell disease (SCD). RBC transfusions improve oxygen-carrying capacity of blood, decrease hemoglobin S levels, and are indicated for the treatment of complications such as stroke, acute chest syndrome, sickle cell hepatopathy and multiorgan failure syndrome. RBC transfusions may also be considered to reduce the frequency of pain crises for those intolerant or non-responsive to hydroxyurea. Prior practice surveys havedemonstrated significant practice variation in the management of patients with SCD with respect to RBC transfusions. The utilization of both simple RBC transfusions and red cell exchange (RCE) is poorly described, and unknown in the Canadian context, including at our center. The objective of this study is to describe RBC utilization at our center in a cohort of patients with SCD. Methods: All adult patients with SCD who have received care [inpatient, outpatient, or emergency department (ED)] at the Ottawa Hospital, from January 2006 to May 2019 were identified for study inclusion. Transfusion and health care utilization data was obtained through to December 2021 from clinical, administrative and laboratory databases at the Ottawa Hospital. Results: A total of 273 patients with SCD were identified. The median age for the cohort was 25 years (IQR 19,33) at first visit, with females comprising 53.9% of the cohort. The median duration of follow-up was 8.1 years (IQR 5,12.4). O-positive was the most frequent blood type (41.8%), and 8 (2.9%) individuals were O-negative. The annual RBC and health care utilization for the study cohort is depicted in Figure 1. The total number of hospital visits during the study period was 23127, with a median of 45 visits (IQR 18,100) per patient. 165 patients (60.4%) received 22538 RBC units with a median of 2 units (IQR 1,19) per patient, per year. 86.5% of the RBC units were infused in the outpatient setting, 12.1% in the inpatient setting and 0.8% in the ED. 40.3% of inpatient hospital visits were associated with an RBC transfusion event, compared to 2.4% of ED encounters. The proportion of RBC units transfused that were O-negative was 29.1% (6557 units). 147 patients received 2205 (9.7%) as simple RBC transfusions. The median number of simple RBC units transfused per patient, per year was 1 unit (IQR 1,2). 88 patients received 20333 RBC units during 2702 RCE sessions (median of 14.5 RCE sessions per patient), with 91.5% occurring in the outpatient setting. Of the 88 patients who received RCE, 64 patients (72.7%) had more than one RCE session, 54 patients (61.4%) had more than 5 RCE sessions and 48 patients (54.5%) had more than 10 RCE sessions. The median number of RBC units transfused per RCE session was 7 (IQR 6,9), with a median duration of 30 days (IQR 28,40) between RCE sessions. Conclusions: RBC transfusion was common in our cohort, with the majority of patients having received at least one RBC transfusion. The largest proportion of transfused RBC units stem from RCE use, which represents a small proportion of on our SCD cohort. O-negative units represented a large proportion of units transfused, despite the predominance of non-group O patients, likely due to both differences in donor and patient blood group phenotypes, and recommendations for extended phenotype matching. With pressure on transfusion medicine to provide appropriately matched units and the scarcity of O-negative units, further data accrual on RBC utilization, particularly assessment of indications, requirements for matching, and review of RCE procedures will define further quality improvement interventions to ensure optimal utilization of RBCs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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

A Retrospective Review of Red Blood Cell Transfusion Practices in a Rural Community Hospital System

Introduction: Anemia is associated with increased length of stay and mortality in hospitalized patients. Red blood cell (RBC) transfusions could be lifesaving intervention and are generally used as a stabilizing measure until underlying etiology of anemia is identified and corrected. However, RBC transfusions have several adverse effects which occasionally could be life-threatening, including transfusion associated infections, immunologic reactions, volume overload, electrolyte imbalances, and iron overload. The decision on RBC transfusions should be based on patient's clinical status and physician's judgment, supported by data from randomized trials. Methods: In efforts to improve RBC transfusion practices in Northern Arizona Healthcare (NAH) facilities, all RBC transfusions between 01/01/2021 and 03/31/2022 were evaluated. Based on randomized clinical trial data, the following RBC transfusion thresholds were considered: Hemoglobin (Hgb) <8 g/dL for hospitalized anemic patients with established cardiovascular disease (CVD) or undergoing surgery, and Hgb <7 g/dL in hemodynamically stable hospitalized patients. Transfusions in pediatric patients, active/suspected blood loss, anemia with hemodynamic instability and massive or recurrent transfusions were excluded from the analysis. For the purpose of this study, RBC transfusion was deemed to be unjustified in cases where only 1 unit of RBC could have been sufficient to raise Hgb level above the specified threshold, however >1 unit was used with no clear justification. Results: A total of 2756 units of RBC transfusions were analyzed in hospitalized patients ages 18-102 years. Three patient groups were identified based on the documented provider justification for RBC transfusions: 1) Hgb <7 g/dL, 2) Hgb <8 g/dL with established CVD or undergoing surgery, 3) "other" who did not meet criteria for the previous groups. In the "other" group, the justification was manually entered by the provider. In the Hgb <7 group, 2004 RBC units were transfused in 1019 patients. Of those, 1440 units were transfused for Hgb level of 6.0-6.9 g/dL in 837 patients, with 273 patients receiving 2-4 units of RBCs when 1 unit could have been sufficient to raise the Hgb level >7 g/dL. Therefore, 303 RBC units were considered unjustified. Also, 83 units were deemed unjustified as they were transfused in 72 patients with pre-transfusion Hgb of ≥7.0 g/dL. In the Hgb <8 group, a total of 711 units were transfused in 500 patients. In the CVD group, 401 units were transfused in 287 patients, of which 260 patients had a Hgb of 7.0-7.9 g/dL. Thirty-four of these patients received 2-3 units when 1 unit was deemed sufficient to increase Hgb >8 (35 unjustified units). Additionally, 5 patients received at least 1 unit of RBC when Hgb was ≥8.0 g/dL (6 unjustified units). In patients undergoing surgery, 213 patients received 310 units. Of those, 150 patients had a Hgb 7.0-7.9 g/dL, 23 of which received >1 units (23 unjustified units). In the group classified as "other", 41 units were transfused in 39 patients. Hgb levels in this group were between 6.7 to 13.3 g/dL. After further evaluation, 18 units transfused in 17 patients were deemed to be unjustified. Discussion: RBC transfusion practices were evaluated in two hospitals in a rural setting in Arizona. From a total of 2756 units, 468 (16.9%) were deemed to be unjustified. The majority of these cases were seen in the Hgb <7 group. This is the first evaluation of RBC transfusion practices at this institution and a stepping stone to implement measures to improve these practices in the future. The next step includes creating an order set module that would not only require providing justification for blood transfusion, but also confirmation of pre-transfusion and desired target Hgb levels. Additionally, it would implement a notification encouraging single unit transfusions when feasible to decrease transfusion associated adverse reactions and cost burden on patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Measurement of post-transfusion red blood cell survival kinetics in sickle cell disease and β-Thalassemia: A biotin label approach.

Red blood cell (RBC) transfusions are an important treatment modality for patients with sickle cell disease (SCD) and β-thalassemia. A subgroup of these patients relies on a chronic RBC transfusion regimen. Little is known about RBC survival (RCS) of the transfused allogeneic RBCs. In this study, we aimed to study the RCS kinetics of transfused RBCs in SCD and β-thalassemia and to investigate factors that determine RCS. We performed a prospective cohort study on fourteen adults with SCD and β-thalassemia disease receiving a chronic transfusion regimen. RCS and the influence of donor and patient characteristics on RCS were assessed by simultaneous transfusion of two allogeneic RBCs using RBC biotinylation. Phenotyping of well-known RBC markers over time was performed using flow cytometry. RCS of the two transfused RBC units was similar in most patients. Although intra-individual variation was small, inter-individual variation in RCS kinetics was observed. Most patients demonstrated a non-linear trend in RCS that was different from the observed linear RCS kinetics in healthy volunteers. After an initial slight increase in the proportion of biotinylated RBCs during the first 24 h, a rapid decrease within the first 10-12 days was followed by a slower clearance rate. These are the first data to demonstrate that patient-related factors largely determine post-transfusion RCS behavior of donor RBC in SCD and β-thalassemia, while donor factors exert a negligible effect. Further assessment and modeling of RCS kinetics and its determinants in SCD and β-thalassemia patients may ultimately improve transfusion therapy.

Real-World Outcomes of Ruxolitinib in Patients With Myelofibrosis Focusing on Red Blood Cell Transfusion: A Multicenter Study From the MPN Working Party of the Korean Society of Hematology

Introduction/BackgroundRuxolitinib is an established treatment for myelofibrosis (MF) that has demonstrated clinical benefit by reducing spleen size and debilitating MF-related symptoms. However, despite the efficacy of ruxolitinib, anemia remains a major adverse event that causes dose modification or discontinuation in real-world practice. Additionally, dependence on red blood cell (RBC) transfusion (TF) is common during treatment; therefore, we explored the outcome of ruxolitinib therapy with a primary focus on RBC TF. Patients/MethodsWe retrospectively reviewed the medical records of 123 MF patients treated with ruxolitinib between January 2012 and April 2020 at eight academic centers in Korea. ResultsAt ruxolitinib initiation, 38 patients (30.9%) underwent ≥ 2 units of RBC TF over 8 weeks. The most common reason for permanent discontinuation was intolerant anemia (10/63, 15.9%). The most common reasons for temporary interruption were nonhematologic toxicity (26/55, 21.1%), anemia (23/55, 18.7%) and thrombocytopenia (13/55, 10.6%). Among the 123 patients in the study, 57 (46.3%), 42 (34.1%), and 40 patients (32.5%) who were receiving or stopped ruxolitinib therapy had a status of RBC TF dependence, long-term RBC TF dependence, or severe RBC TF dependence, respectively. The presence of ≥ 2 units of RBC transfusion over 8 weeks at ruxolitinib initiation was an independent risk factor for persistent RBC TF dependence. ConclusionThe requirement for RBC TF is commonly encountered during treatment of MF with ruxolitinib, particularly among those with pre-existing ≥ 2 units of RBC TF over 8 weeks. For those patients, overcoming the barrier of maintenance TF is demanding.

Palliative Radiotherapy for Bleeding from Unresectable Gastric Cancer Using Three-Dimensional Conformal Technique.

Optimal regimens using recent radiotherapy (RT) equipment for bleeding gastric cancer (GC) have not been fully investigated yet. We retrospectively reviewed the clinical data of 20 patients who received RT for bleeding GC in our institution between 2016 and 2021. Three-dimensional conformal RT was performed. The effectiveness of RT was evaluated by the mean serum hemoglobin (Hb) level and the number of transfused red blood cell (RBC) units 1 month before and after RT. The median first radiation dose was a BED of 39.9 Gy. The treatment success rate was 95% and the rebleeding rate was 10.5%. There was a significant increase in the mean Hb level (8.0 ± 1.1 vs. 9.8 ± 1.3 g/dL, p = 0.01), and a significant decrease in the mean number of transfused RBC units (6.8 ± 3.3 vs. 0.6 ± 1.5 units, p < 0.01). Severe toxicity was observed in two patients (anorexia [n = 1] and gastrointestinal [GI] perforation [n = 1]). Reirradiation was attempted in three patients (for hemostasis [n = 2] and for mass reduction [n = 1]). The retreatment success rate for rebleeding was 100%. GI perforation occurred in two patients who had received hemostatic reirradiation. Palliative RT for bleeding GC using recent technology had excellent efficacy. However, it may be associated with a risk of GI perforation.

Perioperative Bleeding Requiring Blood Transfusions is Associated With Increased Risk of Stroke After Transcatheter and Surgical Aortic Valve Replacement

The authors aimed to investigate the impact of severe bleeding and use of red blood cell (RBC) transfusion on the development of postoperative stroke after surgical (SAVR) and transcatheter aortic valve replacement (TAVR), taken from the FinnValve registry. Nationwide, retrospective observational study. Five Finnish university hospitals participated in the registry. A total of 6,463 patients who underwent SAVR (n=4,333) or TAVR (n=2,130). Patients who underwent TAVR or SAVR with a bioprosthesis with or without coronary revascularization. The incidence of postoperative stroke after SAVR was 3.8%. In multivariate analysis, the number of transfused RBC units (odds ratio [OR], 1.098; 95% confidence interval [CI], 1.064-1.133) was one of the independent predictors of postoperative stroke. The incidence of stroke increased, along with the severity of perioperative bleeding, according to the European Coronary Artery Bypass Grafting (E-CABG) bleeding grades were as follows: grade 0, 2.2% (reference group); grade 1, 3.4% (adjusted OR, 1.841; 95% CI, 1.105-3.066); grade 2, 5.5% (adjusted OR, 3.282; 95% CI, 1.948-5.529); and grade 3, 14.8% (adjusted OR, 7.103; 95% CI, 3.612-13.966). The incidence of postoperative stroke after TAVR was 2.5%. The number of transfused RBC units was an independent predictor of stroke after TAVR (adjusted OR, 1.155; 95% CI, 1.058-1.261). The incidence of postoperative stroke increased, along with the severity of perioperative bleeding, as stratified by the E-CABG bleeding grades: E-CABG grade 0, 1.7%; grade 1, 5.3% (adjusted OR, 1.270; 95% CI, 0.532-3.035); grade 2, 10.0% (adjusted OR, 2.898; 95% CI, 1.101-7.627); and grade 3, 30.0% (adjusted OR, 10.706; 95% CI, 2.389-47.987). Perioperative bleeding requiring RBC transfusion and/or reoperation for intrathoracic bleeding is associated with an increased risk of postoperative stroke after SAVR and TAVR. Patient blood management and meticulous preprocedural planning and operative technique aiming to avoid significant perioperative bleeding may reduce the risk of cerebrovascular complications.

P112: ENERGIZE AND ENERGIZE-T: TWO PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES OF MITAPIVAT IN ADULTS WITH NON--TRANSFUSION-DEPENDENT OR TRANSFUSION-DEPENDENT ALPHA- OR BETA-THALASSEMIA

Background: Thalassemias are characterized by imbalanced globin-chain production resulting in excess α- or β-globin precipitation, hemolytic anemia, and ineffective erythropoiesis.1,2 ATP levels are reduced in thalassemic red blood cells (RBCs), despite increased energy demands.3,4 Mitapivat is an oral activator of RBC pyruvate kinase (PKR), a glycolytic enzyme that regulates ATP production.5 In a phase 2 study of patients with α- or β-non–transfusion-dependent thalassemia (NTDT), twice-daily (BID) dosing with mitapivat increased hemoglobin (Hb) levels by ≥1.0 g/dL in 80% of patients,6 supporting the broadening of mitapivat’s development in thalassemia. Aims: To report the study designs of ENERGIZE (2021-000211-23) and ENERGIZE-T (2021-000212-34), two phase 3 trials to assess the efficacy and safety of mitapivat in adults with α- or β-NTDT or transfusion-dependent thalassemia (TDT), respectively. Methods: Both studies are phase 3, multicenter, randomized, double-blind, placebo-controlled trials (Figure). In ENERGIZE, approximately 171 eligible adults with NTDT will be randomized (2:1) to receive 100 mg mitapivat BID or placebo for 24 weeks. Upon completion, eligible patients can transition to a 5-year, open-label extension. Key inclusion criteria: documented diagnosis of thalassemia (β-thalassemia ± α-globin mutations, Hb E β-thalassemia, or α-thalassemia [Hb H disease]), Hb concentration ≤10.0 g/dL, and NTDT defined as ≤5 RBC units during the 24-week period before randomization and no RBC transfusion ≤8 weeks prior. The primary endpoint is an Hb response defined as a ≥1.0 g/dL increase in average Hb concentration from Week 12 through 24 compared with baseline. Secondary endpoints include patient-reported outcomes, changes in Hb, markers of hemolysis and erythropoiesis, and safety. In ENERGIZE-T, approximately 240 eligible adults with TDT will be randomized (2:1) to receive 100 mg mitapivat BID or placebo for 48 weeks. Upon completion, eligible patients can transition to a 5-year, open-label extension. Key inclusion criteria: documented diagnosis of thalassemia (same genotypes as detailed for the ENERGIZE study), and TDT defined as 6–20 RBC units transfused and no transfusion-free period ≥6 weeks during the 24 weeks before randomization. The primary endpoint is a transfusion reduction response, defined as a ≥50% reduction in transfused RBC units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline. Secondary endpoints include additional measures of transfusion burden, changes in iron markers, and safety. Results: Not yet available. Conclusions: ENERGIZE and ENERGIZE-T are the first pivotal studies to assess a potential treatment across a broad spectrum of patients with thalassemia (ie, patients with TDT and NTDT; α- and β-thalassemias). ENERGIZE and ENERGIZE-T will evaluate the efficacy and safety of mitapivat, a novel, first-in-class oral activator of PKR. Both studies are actively recruiting.

Transfusion-related acute lung injury: A rare case after single packed red blood cell unit transfusion

Transfusion-related acute lung injury: A rare case after single packed red blood cell unit transfusion

Single-Unit Transfusion Is Non Inferior to Double Unit Transfusion in Patients with Hematological Disorders Receiving Allogeneic or Autologous Bone Marrow Transplant or Induction Chemotherapy for Acute Leukemia: The 1versus2 Prospective Multicentric Randomized Clinical Trial

IntroductionAnemia is a common complication of hematological chemotherapy for acute leukemia and following hematopoietic stem cell transplantation (HSCT). Exposure to allogeneic blood transfusions has been associated with unfavorable outcome in several studies in a non-surgical settings. Retrospective studies in hematological intensive unit have suggested that single red blood cell (RBC) unit transfusion policy may reduce the number of RBC used in comparison with a classical double RBC unit transfusion policy, without clinical impact. The aim of the study was to demonstrate that single RBC transfusion was non inferior to the standard double RBC transfusion arm in terms of severe complication or mortality for inpatient with hematological malignancies. Key secondary endpoint, was the comparison of the numbers of RBC units transfused in each arm.MethodIn a phase 3 multicenter randomized trial, 245 adults' patients with acute leukemia requiring intensive chemotherapy or patients receiving autologous or allogeneic HSCT were randomly assigned (1:1) to receive either single RBC unit (1 RBC arm, n=125) per transfusion or double RBC (2 RBC arm, n=120) per transfusion when hemoglobin level was below 8g/dL.The primary composite endpoint was the percentage of patients who developed a grade ≥3 complications defined as stroke, transient ischemic attack, acute coronary syndrome, heart failure, elevated troponin level, intensive care unit transfer, death, new pulmonary infiltrates, and/or transfusion-related infections during hospital stays. The secondary endpoint was the number of red cell units transfused per patient per hospital stay. The primary endpoint was compared between groups by non-inferiority analysis for the proportion risk difference using Farrington-Manning method with a non-inferiority margin of 0.1, in ITT dataset.ResultsHematological disease were as followed: AML (59%), ALL (13.1%), Lymphoma (16.4%), others (11.5%). The median age was 55 years. Baseline characteristics were well balanced between the 2 arms (Figure 1A). A total of 981 and 592 transfusions have been necessary in the 1 RBC arm and 2 RBC arm, respectively. The median of RBC unit per transfusion was 1(1-1) and 2(2-2) in the 1 RBC and 2 RBC arm, respectively. The mean pre transfusion hemoglobin level was 7.49 +/- 0.83 g/dL in the 1 RBC arm and 7.46 +/- 0.67 g/dL in the 2 RBC arm (p=0.275). Hemoglobin level at discharge was 9.35 +/-1.14 g/dL in the 1 RBC arm and 9.58 +/-1.13 g/dL in the 2 RBC arm (p=0.118).The median (IQR) of red-cell units transfused per patient was 7 (4-12) in the single arm and 8 (4-12) in the double arm (p=0.65). The median number of platelet transfusion event was 7 (3.5-11.5) in the 1 RBC arm and 7 (3-13) in the 2 RBC arm (p=0.69). The median (IQR) number of red cell unit transfused per cycle and per day was 7 (3-9) and 0.28 (0.17-0.37) in the 1RBC arm and 6 (4-10) and 0.27 (0.20-0.38) in the 2 RBC arm (p=0.61 and p=0.47).The predefined non-inferiority criteria was achieved with 28 patients developing a serious complication in the 1 CGR arm (22.4%) and 28 patients in the 2 RBC arm (23.3%) (Risk difference 0.009; 95% Confidence interval [-0.0791- 0.0978] (Figure 1B).Conclusion: Single RBC transfusion policy is non inferior to double RBC transfusion policy in hematological intensive care unit for patient receiving a bone marrow transplant or intensive chemotherapy. Single RBC unit transfusion can be used safely in daily clinical practice. The single RBC transfusion policy does not reduce the number of RBC transfusion. [Display omitted] DisclosuresJardin: Genexpath: Patents & Royalties: The author is a potential inventor on a patent application for the LymphoSign, which has been licensed for by Genexpath Patents & Royalties. .

ENERGIZE AND ENERGIZE-T: TWO PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES OF MITAPIVAT IN ADULTS WITH NON–TRANSFUSION-DEPENDENT OR TRANSFUSION-DEPENDENT ALPHA- OR BETA-THALASSEMIA

Thalassemias are characterized by imbalanced globin-chain production resulting in excess α- or β-globin precipitation, hemolytic anemia, and ineffective erythropoiesis. Adenosine triphosphate (ATP) levels are reduced in thalassemic red blood cells (RBCs), despite increased energy demands. Mitapivat is an oral activator of RBC pyruvate kinase (PKR), a glycolytic enzyme that regulates ATP production. In a phase 2 study of patients (pts) with α- or β-non–transfusion-dependent thalassemia (NTDT), twice-daily (BID) dosing with mitapivat increased hemoglobin (Hb) levels by ≥1.0 g/dL in 80% of pts, supporting the broadening of mitapivat's development in thalassemia. The study designs of ENERGIZE (2021-000211-23) and ENERGIZE-T (2021-000212-34), two phase 3 trials to assess the efficacy and safety of mitapivat in adults with α- or β-NTDT or transfusion-dependent thalassemia (TDT), respectively, are reported here. Both studies are phase 3, multicenter, randomized, double-blind, placebo-controlled trials. In ENERGIZE, approximately 171 eligible adults with NTDT will be randomized (2:1) to receive 100 mg mitapivat BID or placebo for 24 weeks (wks). Upon completion, eligible pts can transition to a 5-year, open-label extension. Key inclusion criteria: documented diagnosis of thalassemia (β-thalassemia ±α-globin mutations, Hb E β-thalassemia, or α-thalassemia [Hb H disease]), Hb concentration ≤10.0 g/dL, and NTDT defined as ≤5 RBC units during the 24-wk period before randomization and no RBC transfusion ≤8 wks prior. The primary endpoint is an Hb response defined as a ≥1.0 g/dL increase in average Hb concentration from Wk 12 through 24 compared with baseline (BL). Secondary endpoints include pt-reported outcomes, changes in Hb, markers of hemolysis and erythropoiesis, and safety. In ENERGIZE-T, approximately 240 eligible adults with TDT will be randomized (2:1) to receive 100 mg mitapivat BID or placebo for 48 wks. Upon completion, eligible pts can transition to a 5-year, open-label extension. Key inclusion criteria: documented diagnosis of thalassemia (same genotypes as detailed for the ENERGIZE study), and TDT defined as 6–20 RBC units transfused and no transfusion-free period ≥6 wks during the 24 wks before randomization. The primary endpoint is a transfusion reduction response, defined as a ≥50% reduction in transfused RBC units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-wk period through Wk 48 compared with BL. Secondary endpoints include additional measures of transfusion burden, changes in iron markers, and safety. Not yet available. ENERGIZE and ENERGIZE-T are the first pivotal studies to assess a potential treatment across a broad spectrum of pts with thalassemia (ie, pts with TDT and NTDT; α- and β-thalassemias). ENERGIZE and ENERGIZE-T will evaluate the efficacy and safety of mitapivat, a novel, first-in-class oral activator of PKR. Both studies will start enrollment in 2021.

Association between the length of storage of transfused leukoreduced red blood cell units and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital-acquired infection (HAI) incidence rate in critically ill children. RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion-related immunomodulation due to bioactive substances' release as transfused blood ages. In this secondary analysis of the 'Transfusion Requirement in Paediatric Intensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre-storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21-34 days), and 3) transfusion of 'long-stored' RBCs (≥35 days). All were compared to a 'golden' period (11-20 days), representing the time between 'fresh' and 'stored'. We used quasi-Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI). We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'long-stored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children.

Red Blood Cell Transfusion Volumes According to AIMS65 Scores in Patients with Peptic Ulcer Bleeding.

Fluid supplementation and red blood cell (RBC) transfusions form first-line management strategies to maintain circulating blood volumes in patients with upper gastrointestinal bleeding (UGIB). In this study, we aimed to analyze the utility of the AIMS65 score in predicting the volume of RBC transfusion required in patients with bleeding peptic ulcers. In this single-center, retrospective study, the data of patients admitted between January 2019 and December 2019 with suspected UGIB were retrospectively reviewed. The RBC volume transfused during pre- and postendoscopic hemostasis was measured in relation to various patient factors including the AIMS65 scores. Transfusion rates, the mean number of transfused RBC units, and the duration of hospital stay differed significantly between patients with low AIMS65 scores and those with high AIMS65 scores. Patients with an AIMS65 score of 3 were transfused with more RBC units in the postendoscopic hemostasis period, compared with those with an AIMS65 score of 0, 1, or 2 (with a mean of 4.33 ± 2.07 and 2.67 ± 4.1 units transfused during the pre-endoscopic and postendoscopic hemostasis periods, respectively). Patients with UGIB and with an AIMS65 score of 3 were more likely to require transfusions of RBCs.

Relationship between transfusion burden, healthcare resource utilization, and complications in patients with beta-thalassemia in Taiwan: A real-world analysis.

BackgroundThis study utilized a population‐based claims database to identify patients with beta‐thalassemia and evaluate associations between transfusion burden, healthcare resource utilization (HCRU), and complications.Study design and methodsTaiwan's National Health Insurance Research Database was used to identify patients with beta‐thalassemia (ICD‐10 D56.1) in 2016. Patients with a beta‐thalassemia claim in 2016 were indexed into the study at their first claim on or after January 1, 2001 in the dataset through to December 31, 2016 and followed until the end of study. During the follow‐up period, red blood cell transfusion (RBCT) units, HCRU, iron chelation therapy use, and beta‐thalassemia‐related complications incidence were recorded. Patients were grouped into transfusion burden severity cohorts based on average number of RBCT units per 12 weeks during follow‐up: 0 RBCT units, >0 to <6 RBCT units (mild), ≥6 to <12 RBCT units (moderate), and ≥12 RBCT units (severe).ResultsA total of 2984 patients were included with mean follow‐up of 6.95 years. Of these, 1616 (54.2%) patients had no claims for RBCT units, 1112 (37.3%) had claims for >0 to <6 RBCT units, 112 (3.8%) for ≥6 to <12 RBCT units, and 144 (4.8%) for ≥12 RBCT units per 12 weeks. Transfused patients had significantly more all‐cause HCRU and iron chelation therapy compared with non‐transfused patients during follow‐up. Thalassemia‐related HCRU and risk of liver, endocrine, cardiac, and renal complications were significantly and positively correlated with increases of RBCT units.DiscussionClinical and healthcare resource burden of patients with beta‐thalassemia is closely related to transfusion burden.

Minimally invasive surgery versus sternotomy in native mitral valve endocarditis: a matched comparison.

The present study compared the clinical outcomes between minimally invasive surgery (MIS) and median sternotomy (MS) in patients with native mitral valve infective endocarditis. From 2009 to 2019, a total of 154 patients with acute (n = 131, 85%) or subacute (n = 23, 15%) native mitral valve infective endocarditis were included in the study. One-to-one nearest neighbour propensity score matching considering endocarditis severity using the dedicated De Feo score and 19 other clinically relevant baseline variables resulted in a population of 39 matched pairs. The matched cohort was investigated regarding operative and postoperative outcomes. Both groups showed similar results regarding cardiopulmonary bypass time [MIS: 96 min (77-138), MS: 99 min (88-127); P = 0.780] and aortic cross-clamp time [MIS: 64 min (54-90), MS: 65 min (59-83); P = 0.563], whereas overall operative time was shorter through minimally invasive access [MIS: 138 min (112-196), MS: 187 min (175-230); P = 0.005]. Although the rate of revision for bleeding was similar in both groups [MIS: 12.8% (n = 5), MS: 10.3% (n = 4); P = 1.000], MIS was associated with fewer red blood cell unit transfusions [MIS: 1 unit (0-4), MS: 4 units (2-10); P = 0.001] and fewer fresh frozen plasma unit transfusions [MIS: 0 units (0-0), MS: 1 unit (0-5); P = 0.002]. MIS was associated with a shorter ventilation time [MIS: 708 min (429-1236), MS: 1440 min (659-4411); P = 0.024] and a lower rate of reintubation after extubation [MIS: 5.1% (n = 2), MS: 25.6% (n = 10); P = 0.021]. In patients suffering from native mitral valve infective endocarditis, MIS provides significant clinical benefits over sternotomy in selected patients. 117, 121.

No Association between Age of Transfused Red Cells and 30-Day Mortality in Massively Transfused Patients: Results from the Australian and New Zealand Massive Transfusion Registry

BackgroundClinical trials studying age of transfused red blood cells (RBCs) have found no evidence of benefit from transfusion of fresher RBCs. However, these studies have not included patients requiring massive transfusion for major bleeding, a patient population that may be more susceptible to adverse effects of the RBC storage lesion. Further, no clinical trials have specifically evaluated the safety of transfusing RBCs approaching expiry (30-42 days). We investigated the association between RBC storage time and 30-day mortality in a large cohort of massively transfused patients (5 RBCs within 4 hours, from any bleeding context).MethodsUsing 2007-2015 Australian/NZ Massive Transfusion Registry data from 25 hospitals linked with Australian and New Zealand National Death Index data, we modelled the association between storage time and 30-day mortality in massively transfused patients. Our logistic regression model adjusted for Charlson co-morbidity score, patient age, patient sex, number of RBC units transfused, and bleeding category (cardiothoracic, gastrointestinal, obstetric, surgical, trauma, vascular surgery, or other) with treating hospital as a random-effects grouping variable. Storage time was quantified as the mean storage time of all units each patient received for our primary analysis, and as a binary predictor indicating patients receiving only RBCs older than 30 days for our secondary analysis. As sensitivity analyses, we stratified patients by number of RBC units received and ran our model individually on each stratum containing more than 50 patients receiving equivalent numbers of RBCs in order to eliminate any confounding introduced by comparing patients receiving differing numbers of RBCs. In our stratified sensitivity analyses, in addition to mean storage time of RBC units received by each patient, we tested minimum and maximum storage times of transfused RBC units as predictors.Results4127 patients meeting the massive transfusion definition during the study period had RBC age available. Stratifying on number of RBC units transfused resulted in 19 strata containing more than 50 patients (those receiving 5,6,7,...23 RBC units), comprising 3641 patients (88% of study population). In the analysis of the entire cohort together, we found no significant association between mean storage duration and 30-day mortality (ORST=0.99 [95%CI: 0.98 to 1.01]; p=0.42) or patients transfused with only RBCs >30days old and 30-day mortality (ORST>30d=0.85 [95%CI: 0.52 to 1.37]; p=0.49). In our stratified sensitivity analyses, we found no association between mean storage time and 30-day mortality (OR for a 1-day increase in mean storage time [ORmeanST] range = 0.95 to 1.08 with p>0.05 for entire range). We likewise found no associations between maximum and minimum storage times and 30-day mortality (ORmaxST range = 0.93 to 1.05 with p>0.05 for all but one stratum; ORminST range = 0.94 to 1.04 with p>0.05 for all strata). For all three stratified sensitivity analyses, we observed no trend in ORST across the strata of patients receiving equivalent numbers of RBCs (figure 1 shows the stratified analysis with mean storage time as the predictor).ConclusionsWe found no association between storage time of transfused RBCs and 30-day mortality in a large cohort of massively transfused patients. Our findings were consistent both for the cohort as a whole and within strata of patients receiving equivalent numbers of RBC transfusions. Additionally, we observed no association when we modelled storage duration as maximum RBC age, minimum RBC age, or when we considered patients receiving only RBCs >30 days old. Our conclusions are consistent with recent large randomised trials which have not demonstrated mortality benefit from transfusing fresher RBCs. Differences in our findings and those of previous observational studies reporting correlations between storage time and mortality may be due to methodological differences: specifically, our stratified analysis eliminated the potential confounding effect of number of RBCs transfused, and we more accurately modelled the storage lesion as a continuous function by using mean storage age rather than comparing patients who received only RBCs above or below arbitrary storage time thresholds. In conclusion, we find no evidence that fresher blood leads to better clinical outcomes in massively transfused patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of Red Blood Cell Transfusion Intensity on Progression-Free Survival in Lower-Risk MDS Patients Included in the European Leukemianet MDS Registry

Abstract Background Progression-free survival (PFS) of lower-risk (LR) MDS patients treated with red blood cell transfusions (RBCT) is usually reduced, but whether the RBCT intensity is important for prognosis is unknown. The EUMDS Registry contains data on 2,192 newly diagnosed LR-MDS patients from 16 European countries and Israel, collected at diagnosis and at 6 months intervals.The aim of this analysis is to assess the effect of RBCT intensity on PFS of patients with LR-MDS in a prospective, observational setting. MethodsData on the number of RBCT units received during each visit-interval were analyzed using proportional hazards regression with time-varying co-variates. The cumulative dose received at the end of each interval was divided by the time since the beginning of the interval in which the first RBCT was received rather than for each visit-interval, to give an overall dose density. Dose density rises over time when RBCT intensity increases over time, but declines when patient becomes RBCT independent after treatment. In Cox regression with time-varying covariates, PFS was adjusted by relevant confounders, including age, gender, patient condition (proxied by EQ-5D index), and number of cytopenias at diagnosis. We analyzed a cohort of 1,509 patients with at least 3 visit reports available. Within this group 476 patients have died and 118 patients have progressed to higher-risk MDS or AML, which were defined as events. ResultsPatients with ring sideroblastic MDS (RS-MDS) received more frequently RBCT after diagnosis compared to non-RS-MDS (60% vs 54%). Very low-risk patients according to IPSS-R received RBCT less often compared to intermediate risk patients (35% vs 69%). Age, gender, presence of co-morbidities, and countries influenced RBCT dependency and RBCT rate. The transfused patients were subdivided in 3 groups according to the maximum RBCT rate over time: low rate ( 2 units/month) in order to analyse the impact of the RBCT rate in more detail (figure A). Unadjusted overall PFS stratified this way, is shown in figure B. Univariate analysis of the 404 patients transfused at a high rate showed a strong association of age (p ConclusionThe negative effect of RBCT treatment on PFS already occurs at low RBCT densities below 2 units/month and before 25 units of RBCT have been transfused. This indicates that the RBCT dependency, even at relatively low intensities, may be considered as an indicator of poor prognosis for survival. Download : Download high-res image (93KB) Download : Download full-size image Figure . Disclosures Fenaux: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Sanz: Gamida Cell: Research Funding. Germing: Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Almeida: Servier: Consultancy; Alexion: Honoraria; Novartis: Consultancy; Celgene: Consultancy; Bristol Meyer Squibb: Honoraria. Itzykson: Janssen: Research Funding; Novartis: Research Funding. Park: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hospira/Pfizer: Research Funding; Celgene: Research Funding. de Witte: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Cilag: Research Funding.

Rapid Blood Transfusion: The Importance of Hemodilution and Needleless Connectors.

Introduction: Large-bore cannulas are critical to administering IV fluids and blood products during resuscitation and treatment of hemorrhage. Although catheter flow rates for crystalloid solutions are well defined, rapid administration of blood products is poorly characterized. In this in vitro study, we examined the effects of hemodilution and needleless connectors on red blood cell (RBC) flow rates.Methods: To determine RBC flow rates through large-bore cannulae, a crystalloid solution (Normosol®, Hospira, Lake Forest, IL) or RBC units were warmed and delivered under pressure (360 mmHg) using a Level 1 H-1200 Fast Flow Fluid Warmer (Smiths Medical, St. Paul, MN). Flow rates for crystalloid, packed RBCs and diluted RBCs were determined using a stopwatch. Additionally, the effect of the MaxPlus® clear needleless connector (CareFusion, San Diego, CA) was measured in all three infusion groups.Results: Flow rates for undiluted RBC units were 53% slower than crystalloid solution (220 mL/min vs. 463 mL/min; p=0.0003), however, when RBC units were diluted to a hematocrit of ~30% flow rate improved to 369 mL/min (p=0.005). The addition of the MaxPlus® needleless connector reduced flow of crystalloid solution by 47% (245 mL/min; p=0.0001), undiluted RBCs by 64% (78 mL/min; p=0.01), and diluted RBCs by 51% (180 mL/min; p=0.00003). Compared to undiluted RBC units, hemodilution increased RBC delivery rate through a MaxPlus® connector by 130% (p=0.004) and by 68% (p=0.02) when the catheter was directly connected to the Level 1 tubing (MaxPlus® excluded).Conclusion: In settings requiring rapid transfusion of RBC units, needleless connectors should not be used and hemodilution should be considered in order to decrease the time required to deliver an equivalent red cell mass.

Mortality and Transfusion Requirements in COVID-19 Hospitalized Italian Patients According to Severity of the Disease

There is paucity of data on the transfusion need and its impact on the overall mortality in patients with COVID-19. We explored mortality in hospitalized patients with COVID-19 who required transfusions. Information on clinical variables and in-hospital mortality were obtained from medical records of 422 patients admitted to medical wards or the Intensive Care Unit (ICU). In-hospital mortality occurred in 147 (34.8%) patients, 94 (63.9%) of whom were admitted to the ICU. The median fatalities age was 77 years (IQR 14). Overall, 100 patients (60 males) received transfusion during hospitalization. The overall mortality was significantly and independently associated with age, ICU admission, Chronic Kidney Disease (CKD), and the number of transfused Red Blood Cell (RBC) units. Specifically, CKD was associated with mortality in patients admitted to medical wards, whereas the number of transfused RBC units predicted mortality in those admitted to the ICU. Transfusion strongly interacted with the admission to ICU (OR: 9.9; 95% CI: 2.5–40.0). In patients with COVID-19, age is one of the strongest risk factors in predicting mortality independently of the disease’s severity. CKD confers a higher risk of mortality in patients admitted to medical wards. In those admitted to the ICU, the more RBC units are transfused, the more mortality increases.