Received Red Blood Cell Transfusion Research Articles

Red Blood Cell Transfusions in Patients with Advanced Cancer Receiving Home Palliative Care.

Background: Red blood cell (RBC) transfusion is the standard treatment for anemia in advanced cancer. Nevertheless, guidelines for managing this condition are still not exhaustive. Objective: To investigate frequency, timing, and clinical characteristics associated with RBC transfusions in patients with advanced cancer assisted by at-home oncological care service and to evaluate the association between parameters at the entry and the possibility of receiving RBC transfusions during homecare. Design: Retrospective observational study without medication. Setting/Subjects: Patients with advanced cancer entered in homecare during 2021 living in Bologna (Italy). Measurements: Gender, tumor primary site, oncological therapy, and symptoms at the entry were considered as possible factors in a binary logistic regression for the possibility of receiving at least one RBC transfusion during assistance. Data about transfusions were analyzed, and the transfusion history for each patient from the entry to death was traced. Results: Among the 1108 patients admitted, 179 (16.2%) were given at least one RBC transfusion during homecare. Genitourinary, hematological malignancies, and being still in therapy for advanced cancer are associated with a higher probability of receiving RBC transfusion during assistance (p = 0.017, p < 0.001, and p = 0.032, respectively). Half of the patients (52%) underwent RBC transfusions less than a month before death. Duration of the assistance was correlated with the period from last transfusion to death (p < 0.001). Conclusion: Hematological and genitourinary cancer and being in simultaneous care at the entry were associated with transfusion. Although the appropriateness of this treatment remains to be defined in this population, transfused patients frequently received "late in life" transfusions.

The incidence of donor white blood cell survival (transfusion-associated microchimerism) in Australian pediatric patients.

Donor leucocyte survival following red blood cell (RBC) transfusion, known as transfusion-associated microchimerism (TAM), can occur in some patients. In Australia, despite the introduction of leucocyte filtration (leucodepletion) during RBC manufacture, TAM has been detected in adult trauma patients. However, the incidence of TAM in Australian pediatric patients has not been analyzed. Patients aged 0-16 years were recruited across two cohorts. Retrospective participants had RBC transfusion between January 1, 2002 and November 15, 2017 and prospective participants received RBC transfusion between December 1, 2016 and November 25, 2020. Twelve bi-allelic insertion/deletion (InDel) polymorphisms were used to detect microchimerism amplification patterns using real-time PCR (RT-PCR) and droplet digital PCR (ddPCR). Of the retrospective cohort (n = 40), six patients showed amplification of InDel sequences indicating potential microchimerism. For three patients, minor InDel sequences were detected using RT-PCR only, two patients had minor InDel amplification using ddPCR only, and one patient had minor InDel amplification that was confirmed using both techniques. Amplification of minor sequences occurred in three patients who had received a bone marrow transplant in addition to RBC transfusion. In the prospective cohort (n = 25), no InDel amplification indicating potential microchimerism was detected using RT-PCR. Cell-based therapies had been administered in three patients where microchimerism amplification patterns were detected. Three patients have microchimerism that may be attributed to RBC transfusion. In prospective patients, who received leucodepleted and gamma-irradiated RBC units, no potential microchimerism amplification were detected. ddPCR may be a suitable technique for TAM analysis but requires further evaluation.

Risk factors associated with anemia of prematurity requiring red blood cell transfusion in very low birth weight infants: a retrospective study

BackgroundAnemia of prematurity (AOP) is prevalent among very low birth weight infants (VLBWIs). Red blood cell (RBC) transfusions, while necessary for managing AOP, have been linked to adverse neonatal outcomes.MethodsThis retrospective study analyzed the medical records of 98 VLBWIs (24–31 weeks gestation) admitted to the Chungbuk National University Hospital neonatal intensive care unit. Infants were categorized based on RBC transfusion status and birth weight (< 1000 g and 1000–1499 g). Clinical outcomes between the groups were compared.ResultsOf the 98 infants, 35 (35.7%) received RBC transfusions. The RBC transfusion group exhibited significantly higher incidence of bronchopulmonary dysplasia (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\ge\\:\\:$$\\end{document}moderate), prolonged invasive mechanical ventilation, intraventricular hemorrhage (grades 1–2), extended time to full enteral feeding, and extended total parenteral nutrition (TPN) compared to the non-RBC transfusion group. Birth weight was inversely correlated with the number of RBC transfusions (p = 0.004). The duration of invasive mechanical ventilation and TPN administration were positively associated with the number of RBC transfusions (p < 0.001 and p = 0.025, respectively).ConclusionsThe RBC transfusion group experienced more comorbidities than the non-transfusion group. Birth weight, duration of invasive ventilation, and duration of TPN were associated with the number of RBC transfusions. Strategies to reduce the duration of invasive ventilation and early discontinuation of TPN may mitigate the need for RBC transfusions in AOP.

Racial and ethnic differences in transfusion rates in adolescent scoliosis surgery: Preoperative anemia as a mediator of disparity

AbstractBackgroundPediatric patients from minoritized racial and ethnic groups receive red blood cell (RBC) transfusions more frequently while undergoing major surgical procedures. Our objective was to identify the contribution of preoperative anemia to racial and ethnic differences in RBC transfusion rates in adolescent spine surgery.Study Design and MethodsThis is a multicenter, retrospective cohort study of the National Surgical Quality Improvement Program Pediatric database, 2016 to 2021 for patients in the United States and Canada.ResultsAdolescents identifying as non‐Hispanic Black, Hispanic, and other race/ethnicity presented with higher rates of preoperative anemia than non‐Hispanic White adolescents (16.3%, 10.6%, and 9.9%, vs. 7.8%, respectively; p &lt; .0001) and were transfused at higher rates (14.4%, 11.9%, 16.5%, vs. 10.0%, respectively; p &lt; .0001). Minoritized groups demonstrated higher adjusted odds of RBC transfusion compared with non‐Hispanic Whites (non‐Hispanic Black: aOR 1.45 95% CI 1.26–1.65, Hispanic: aOR 1.17 95% CI 0.96–1.41, other race/ethnicity: aOR 1.63 95% CI 1.26–2.09). Of the total effect of minoritized race and/or ethnicity on RBC transfusion, 13.9% was attributed to the indirect effect through preoperative anemia.DiscussionIn this cohort study, patients from minoritized racial and ethnic groups received RBC transfusions at a higher rate than non‐Hispanic White patients, and the difference was partially mediated by preoperative anemia. Future efforts to minimize transfusions and improve health equity should target this modifiable risk factor alongside other sources of disparity and discrimination.

Role of red blood cell (RBC) transfusions in patients with prolonged mechanical ventilation during weaning process

Patients undergoing long-term ventilation often show anemia. The aim of the study was to investigate the duration and success of weaning from mechanical ventilation in patients with RBC transfusion. A retrospective analysis of patient data from a weaning unit was performed. Transfused and non-transfused patients were matched using a propensity score. Of the 249 patients in the database, 31 transfused and the same number of non-transfused cases with similar disease severity as measured by the Simplified Acute Physiology Score (SAPS) could be analyzed. Additional sensitivity analyses were performed. In the group of transfused patients, the difference in weaning duration was longer than in non-transfused patients (1.35 days and 3.26 days, respectively). Weaning success also varied. The risk of weaning failure was twice as high in the group of transfused patients. The groups also differed in terms of mortality, 25.8% of the transfused patients died, while in the non-transfused patients the mortality rate was 6.5%. The risk of death was increased in patients who received RBC transfusion. The differences were not statistically significant. A high proportion of patients with prolonged mechanical ventilation have anemia. RBC transfusion does not improve their prognosis. The need for transfusion is associated with higher mortality and longer duration of weaning in this population. The indication for RBC transfusion should therefore be restrictive.

Red blood cell transfusion and mortality after transcatheter aortic valve implantation via transapical approach: A propensity-matched comparison from the TRITAVI registry

ObjectiveBleeding is frequent during transcatheter aortic valve implantation (TAVI), especially when performed through a transapical approach (TA), and is associated with a worse prognosis. The present study aims to test the implication of red blood cell (RBC) transfusion and the optimal transfusion strategy in this context. MethodsAmong 11,265 participants in the multicenter TRITAVI (Transfusion Requirements in Transcatheter Aortic Valve Implantation) registry, 548 patients (4.9%) who received TA-TAVI at 19 European centers were included. One-to-one propensity score matching was performed to reduce treatment selection bias and potential confounding among transfused versus non-transfused patients. The primary endpoint of the study was the 30-day occurrence of all-cause mortality. Results209 patients (38 %) received RBC transfusions. The primary endpoint occurred in 47 (8.6 %) patients. Propensity score matching identified 188 pairs of patients with and without RBC transfusion. In the propensity score-matched analysis, RBC transfusion was associated with increased 30-day mortality (HR 3.35, 95 % CI 1.51 – 7.39; p = 0.002). At multivariable cox regression analysis, RBC transfusion was an independent predictor of 30-day mortality (HR 3.07, 95 % CI 1.01–9.41, p = 0.048), as well as baseline ejection fraction (HR 0.96, 95 % CI 0.92–0.99, p = 0.043), and acute kidney injury (HR 3.95, 95 % CI 1.11–14.05, p = 0.034). ConclusionsRBC transfusion is an independent predictor of short-term mortality in patients undergoing TA-TAVI, regardless of major bleeding.Clinical trial registration: https://www.clinicaltrials.gov Unique identifier: NCT03740425.

Paradigm shift in transfusion practices during early COVID-19 pandemic: A single center retrospective study

BACKGROUND The advent of coronavirus disease 2019 (COVID-19) unveiled the worst national blood crisis that the United States had witnessed in over a decade. With the pandemic influencing the different stages of the acquisition of blood products outside the hospital setting, we aimed to explore the possible barriers contributing to the shortage of blood products within the medical community. AIM To assess the adherence to restrictive blood transfusion practices for patients in the COVID era and pre-COVID era. METHODS We conducted a retrospective cross-sectional study on hospitalized patients distinguishing the pattern of blood transfusion during the COVID and pre-COVID era in a community hospital. Data was tabulated to include the number of red blood cell (RBC) transfusions and if transfusions met restrictive blood transfusion criteria as per institutional guidelines. Chi-square was applied to test the statistical association between qualitative variables. Unpaired t test and Mann Whitney U test were applied respectively to test the mean difference of quantitative variables. RESULTS A total of 208 patients were included in the study, of which 108 were during COVID era and 100 were during pre-COVID era. The leading reason for admission in both the COVID era and pre-COVID era transfused patients was shortness of breath (53.7% and 36% P = 0.001), followed by gastrointestinal bleeding (25.9% and 21% P = 0.001). There was a higher percentage of RBC transfusions in the intensive care unit in the COVID-era group than in the pre-COVID era group (38.9% vs 22%, P = 0.008). The restrictive transfusion criteria were met in 62% vs 79% in the COVID and pre-COVID eras, respectively (P = 0.008). CONCLUSION The COVID-era group received RBC transfusions with less stringent adherence to restrictive blood transfusion practices in comparison to pre-COVID era group.

RBC transfusion and necrotizing enterocolitis in very preterm infants: a multicenter observational study

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro–Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.

Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial

BackgroundMinimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. MethodsThis is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. ResultsThe primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. ConclusionThe trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. Study registrationThis trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Impact of Red Blood Cell Transfusion on Subsequent Cardiovascular Events in Patients with Acute Heart Failure and Anemia.

Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.

Anaemia and red blood cell transfusion in women with placenta accreta spectrum: an analysis of 38,060 cases

Placenta accreta spectrum (PAS) has become a significant life-threatening issue due to its increased incidence and associated morbidity and mortality. Pregnancy is often associated with states of anaemia, and severe maternal haemorrhage represents a major risk factor for red blood cell (RBC) transfusion. The present study retrospectively analyzed the prevalence of anaemia, transfusion requirements and outcome in women with PAS. Using data from the German Statistical Office pregnant patients with deliveries hospitalized between January 2012 and December 2021 were included. Primary outcome was the prevalence of anemia and administration of RBCs. Secondary outcome were complications in women with PAS who received RBC transfusion. In total 6,493,606 pregnant women were analyzed, of which 38,060 (0.59%) were diagnosed with PAS. The rate of anaemia during pregnancy (60.36 vs. 23.25%; p < 0.0001), postpartum haemorrhage (47.08 vs. 4.41%; p < 0.0001) and RBC transfusion rate (14.68% vs. 0.72%; p < 0.0001) were higher in women with PAS compared to women without PAS. Women with PAS who had bleeding and transfusion experienced significantly more peripartum complications than those who did not. A multiple logistic regression revealed that the probability for RBC transfusion in all pregnant women was positively associated with anaemia (OR 21.96 (95% CI 21.36–22.58)). In women with PAS, RBC transfusion was positively associated with the presence of renal failure (OR 11.27 (95% CI 9.35–13.57)) and congestive heart failure (OR 6.02 (95% CI (5.2–7.07)). Early anaemia management prior to delivery as well as blood conservation strategies are crucial in women diagnosed with PAS.

Red blood cell transfusion in patients undergoing elective primary glioblastoma resection.

Red blood cell (RBC) transfusion in patients undergoing major elective cranial surgery is associated with increased postoperative morbidity and mortality. This study aims to identify the clinical outcome of transfused glioblastoma patients undergoing primary surgical tumor resection and identify risk factors for RBC transfusion. Between 2009 and 2019, 406 patients underwent elective primary glioblastoma resection. For multivariate analysis to assess risk factors for RBC transfusion, logistic regression was conducted. The impact of RBC transfusion on overall survival was assessed using Kaplan-Meier analysis. In total, 36 (8.9%) patients received RBC transfusion. Preoperative anemia rate was significantly higher in transfused patients compared to patients without RBC transfusion (33.3 vs 6.5%; p<0.0001). Postoperative complications as well as hospital length of stay (LOS) (p<0.0001) were significantly increased in transfused patients compared to non-transfused patients. After multivariate analysis, risk factors for RBC transfusion were preoperative anemia (p<0.0001), intraoperative blood loss (p<0.0001), female gender (p=0.0056) and radiation (p=0.0064). Kaplan-Meier curves revealed that RBC transfusion and being elderly (age ≥75 years) were relevant for overall survival. RBC transfusion is associated with increased postoperative morbidity and mortality in patients undergoing elective primary glioblastoma resection. Preoperative anemia and intraoperative blood loss are major risk factors for RBC transfusion. Preoperative anemia management and blood conservation strategies are crucial in patients undergoing elective primary glioblastoma resection.

Anemia, red blood cell transfusion and administration of blood products in obstetrics: a nationwide analysis of more than 6 million cases from 2011-2020.

The prevalence of anemia is high, especially in obstetrics. There is large evidence, that anemia during pregnancy is associated with increased maternal morbidity and mortality. Anemia and peripartum hemorrhage remain the main causes for transfusion of red blood cells (RBC). Patient Blood Management (PBM) reduces the need for RBC transfusion significantly. The present study retrospectively analyzed the impact and prevalence of anemia and RBC transfusion on pregnant women. Data were retrieved from the German Statistical Office on pregnant women who delivered in hospital between January 1st 2011 and December 31st 2020. The prevalence of anemia, peripartum hemorrhage, comorbidities, administration of blood products and complications were analyzed. A total of 6,356,046 pregnant women were analyzed of whom 78,257 (1.23%) received RBC transfusion (RBC transfusion group) and 6,277,789 (98.77%) did not receive RBC transfusion (non-RBC transfusion group). In all women analyzed anemia rate was 23.74%. The rates of anemia during pregnancy (70.39 vs 23.15%; p<0.0001), postpartum hemorrhage (41.42 vs 4.35%; p<0.0001), hospital length of stay (127.5 vs 87.08 hours; p<0.0001) and single complications were higher in women with RBC transfusion compared to women without RBC transfusion. The prevalence of anemia and the increased risk for RBC transfusion show that there is great potential for effective implementation of PBM in obstetrics. The treatment of anemia during pregnancy and reduction of RBC transfusions will decrease maternal morbidity and mortality.

Sex Differences in Red Blood Cell Transfusions and 30-Day Mortality in Cardiac Surgery: A Single Center Observational Study.

In cardiac surgery, women have higher short-term mortality and a higher risk of receiving red blood cell (RBC) transfusions than men. This study's aim was to evaluate possible sex differences in RBC transfusions in cardiac surgery and their association with preoperative hemoglobin levels, body mass index, and 30-day mortality. A single-center retrospective study was conducted with 1583 patients (1181 men and 402 women) undergoing cardiac surgery. A total of 64.4% of the women and 33.0% of the men received an RBC transfusion. In a multivariable analysis, female sex was an independent predictor of RBC transfusion (OR 3.88, 95% CI 2.95-5.11, p < 0.001). Other independent predictors of RBC transfusion were age, preoperative hemoglobin level, and body mass index. The women were more likely to receive RBC transfusions than the men, regardless of the type of cardiac surgery. Decreased transfusion risk was found in all higher-than-normal weight categories in the women, but only in the severe obesity category in the men. Preoperative hemoglobin was similarly associated with RBC transfusion in the men and women. The crude 30-day mortality rate was higher in the women than in the men (2.5% vs. 0.9%, p = 0.018). In both sexes, RBC transfusion was associated with an increased probability of death within 30 days.

Transfusion practices in intensive care units: An Australian and New Zealand point prevalence study

ObjectiveTo describe current transfusion practices in intensive care units (ICUs) in Australia and New Zealand, compare them against national guidelines, and describe how viscoelastic haemostatic assays (VHAs) are used in guiding transfusion decisions. Design, setting and participantsProspective, multicentre, binational point-prevalence study. All adult patients admitted to participating ICUs on a single day in 2021. Main outcome measuresTransfusion types, amounts, clinical reasons, and triggers; use of anti-platelet medications, anti-coagulation, and VHA. ResultsOf 712 adult patients in 51 ICUs, 71 (10%) patients received a transfusion during the 24hr period of observation. Compared to patients not transfused, these patients had higher Acute Physiology and Chronic Health Evaluation II scores (19 versus 17, p = 0.02), a greater proportion were mechanically ventilated (49.3% versus 37.3%, p < 0.05), and more had systemic inflammatory response syndrome (70.4% versus 51.3%, p < 0.01). Overall, 63 (8.8%) patients received red blood cell (RBC) transfusions, 10 (1.4%) patients received platelet transfusions, 6 (0.8%) patients received fresh frozen plasma (FFP), and 5 (0.7%) patients received cryoprecipitate. VHA was available in 42 (82.4%) sites but only used in 6.6% of transfusion episodes when available. Alignment with guidelines was found for 98.6% of RBC transfusions, but only 61.6% for platelet, 28.6% for FFP, and 20% for cryoprecipitate transfusions. ConclusionsNon-RBC transfusion decisions are often not aligned with guidelines and VHA is commonly available but rarely used to guide transfusions. Better evidence to guide transfusions in ICUs is needed.

OMS906, a Novel Alternative Pathway MASP-3 Inhibitor, Normalizes Hemoglobin Levels and Increases Clone Size in Treatment-Naïve PNH Patients

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disorder characterized by hemolytic anemia in combination with various degrees of marrow failure. PNH is driven by dysregulation of the complement system where the absence of CD55 and CD59 cell surface proteins leads to red blood cell (RBC) lysis. Untreated PNH can lead to debilitating anemia, thrombosis, fatigue, and increased mortality. Terminal complement inhibition attenuates intravascular hemolysis (IVH) but inevitably leads to extravascular hemolysis (EVH). Proximal and alternative pathway (AP) inhibition block both IVH and EVH, as demonstrated with C3, Factor B, and Factor D inhibitors. Mannan-binding lectin-associated serine protease-3 (MASP-3) activates pro-Factor D, thus activating the AP upstream of Factor D. OMS906 is a highly selective humanized mAb that binds to and inhibits MASP-3. In a Phase 1 study in healthy subjects, OMS906 was well tolerated and provided substantial MASP-3 inhibition. In the present study, safety and efficacy of OMS906 were evaluated in complement-inhibitor treatment-naïve patients with PNH. Methods: This is an ongoing, single-arm, open-label, Phase 1b proof-of-concept clinical trial (NCT05889299; EudraCT 2022-002450-22) evaluating safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of OMS906 in adults with PNH. Eligibility criteria include: confirmed PNH diagnosis by flow cytometry (RBC clone size &amp;gt;10%); complement-inhibitor treatment-naïve or inadequate response to C5 inhibitors; and baseline hemoglobin (Hgb) &amp;lt;10.5 g/dL. Patients received 5 mg/kg subcutaneous (SC) OMS906 every 4 weeks, the lowest exposure cohort in this study. Primary endpoints are safety and tolerability. Secondary endpoints include changes from baseline in Hgb and lactate dehydrogenase (LDH) levels, RBC clone size, and absolute reticulocyte count; achievement of Hgb ≥12 g/dL or an increase of ≥2 g/dL; and transfusion independence. Planned enrollment was approximately 10 patients. Results: This pre-specified interim analysis included data available as of July 20, 2023. All patients (N=11) included in this analysis were complement-inhibitor treatment-naïve (55% female; mean age 41 years [range 27-72]). The majority of patients (64%) received RBC transfusions in the 12 months prior to OMS906 treatment. Co-existing conditions included iron deficiency (n=6), chronic renal failure (n=3), aplastic anemia (n=2), and myelodysplastic syndrome (MDS; n=2). At baseline (N=11), mean Hgb was 7.0 g/dL (median 6.4 g/dL, range 3.9-10.4 g/dL) and LDH was 1835 U/L (median 1831 U/L, range 905-3480). To date, all patients have received ≥2 doses of OMS906 with 4 patients having received ≥6 doses. OMS906 was well tolerated. The most common adverse events (AEs) in ≥20% of patients were increased thrombocytopenia (36%), neutropenia (27%), and itching (27%). No patients experienced clinical breakthrough hemolysis. There were no major adverse vascular events, treatment-related serious AEs, discontinuations, or deaths. Following initiation of OMS906, mean Hgb increased from baseline by 3.1 g/dL ( P&amp;lt;0.001) at 4 weeks (N=11), and by 9.5 g/dL ( P=0.016) at the latest timepoint of 24 weeks (n=3) [Figure 1]. Among patients receiving ≥2 doses, all but 3 experienced gender-specific normalization of Hgb levels. The remaining patients had MDS (n=2) or marrow failure (n=1). No patients required transfusions following OMS906 treatment. Mean LDH levels decreased from baseline by 1483 U/L (&amp;gt;80%; P&amp;lt;0.001) at 4 weeks (N=11) and by 1939 U/L ( P=0.004) at 24 weeks (n=3). Three patients had increases in LDH, suggesting initiation of hemolysis at the end of a dosing period. Mean absolute reticulocyte counts decreased from baseline by 87,000-122,000 ×10 9/L at all timepoints. Mean PNH RBC clone size increased by up to 38.6% (n=6; P=0.016) versus baseline. Conclusion: In this interim analysis, MASP-3 inhibitor OMS906 was well tolerated with no safety signals of concern. Once-monthly SC OMS906 resulted in clinically meaningful, beneficial effects on Hgb, LDH, and RBC clone size in treatment-naïve PNH patients. OMS906 dose escalation guided by occurrence of subclinical hemolysis is being evaluated with the goal of achieving quarterly dosing.

Safety and efficacy of least incompatible red cell units in autoimmune hemolytic anemia: A prospective analysis of hemoglobin increment and hemolysis after transfusion

Abstract BACKGROUND: Red blood cell (RBC) transfusion is a challenge in autoimmune hemolytic anemia (AIHA) patients due to pan reactivity and crossmatch incompatibility. Apprehensions about the safety and efficacy of least incompatible (best-matched) red cells are common among treatment providers. AIM: A primary objective was to study the effect of RBC transfusion on hemolysis parameters (hemoglobin [Hb], serum bilirubin, serum lactate dehydrogenase [LDH], and reticulocyte count) in AIHA patients. SETTINGS AND DESIGN: This was a hospital-based prospective observational study conducted on 40 AIHA patients attending the department of internal medicine from January 2020 to July 2021 who received RBC Transfusions. METHODOLOGY: Blood samples were collected for evaluating hemolysis parameters: Hb, reticulocyte count, serum bilirubin, and serum LDH before transfusion and compared with the same parameters within 12 h after transfusion. STATISTICAL ANALYSIS: Analysis was done by SPSS software Version 16. Paired t-test was used to find the effect of RBC transfusion on hemolysis parameters and independent t-test was used to compare the effect of compatible and incompatible RBC transfusions. RESULTS: The median age at presentation was 42 years with a female preponderance (67.5%). Majority of the patients belong to warm AIHA (73%) and Secondary AIHA (60%). Compatible RBC units could be provided to 57% of cases and 43% were transfused with the least incompatible units. The mean pretransfusion Hb in AIHA was 4.3 mg/dl and showed a statistically significant increase after transfusion (P &lt; 0.001). A significant difference between reticulocyte levels of compatible and incompatible transfusions was noted with a P = 0.025. No statistically significant difference noticed in Hb, serum LDH, serum bilirubin levels between compatible and incompatible RBC transfusions. CONCLUSION: RBC transfusions in AIHA patients provide Hb increment similar to other anemic patients. RBC transfusions should not be denied in AIHA patients in view of hemolysis and best-matched units also may be transfused in indicated cases.

Myelodysplastic Syndrome Red Blood Cell Physiology Abnormalities and Their Correlation with Disease Risk and Therapeutic Interventions

PV and KT as well as VP and MA contributed equally Introduction: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, different degree of cytopenias, and increased risk of transformation to AML. Anemia constitutes a main clinical manifestation contributing to increased morbidity and mortality. It is currently managed with red blood cell (RBC) transfusions, erythropoiesis stimulating agents (EPO), and recently,with luspatercept. The latter enhances late stage erythropoiesis and is indicated for Ring Sideroblasts (RS) MDS resistant to EPO. Several lines of evidence suggest that MDS pathophysiology is associated with structural and functional distortions of mature red cell (RBCs), such as hemolysis that in rare instances include acquired lesions like hemoglobinopathies and membranopathies.These abnormalities add variability to the clinical MDS phenotypes and could serve as biomarkers for early diagnosis or monitoring. However, they have been scarcely investigated. Patients and methods: We examined 40 MDS patients and 12 healthy sex- and age-matched controls. According to the IPSS-Rrisk stratification system, 8 patients were High Risk (HR) and 32 patients Low Risk (LR)MDS, of whom 8 under EPO (EPO-LR) and 4 under luspatercept (luspatercept-LR) treatment. None of them had received RBC transfusions in the past three months. Following full blood count analyses and RBC fractionations, we measured hemolysis (basal, osmotic, mechanical, and oxidative), eryptosis and oxidative stress, as well as the antioxidant capacity of the plasma through spectrophotometry,fluorometry and flow cytometry. Results: Compared to controls, the cohort of MDS patients was characterized by anemia (Hb 10.7 vs 13.6g/dL) and significantly higher HDWand RDW (17.5 vs. 13.4%) indexes. RBCs exhibited signs of eryptosis (RBC calcium concentration 7063±1443 vs. 6027±1541 RFU/mg; PS surface exposure 0.61±0.45 vs. 0.33±0.17%) and oxidative stress (higher metHb/oxyHb ratio; membrane-bound hemichromes 45.0±15.3 vs. 30.2±13.3). About 18% of the patients presented spontaneous hemolysis. Clinical severity correlated with the levels of cytopenias, and oxidative hemolysis. Anemia correlated positively with the age, and the levels of membrane-bound hemichromes, eryptosis and intracellular reactive oxygen species (ROS). According to ROC analysis, the combination of RDW, metHb/oxyHb ratio, and total Hb concentration is predictive of MDS, across all IPSS-R categories(area under the curve: 0.908; Figure 1). We then examined the subgroups of MDS patients. Apart from the RDW, the LR-MDS subgroup exhibited on average normal RBC features, in opposite to the more anemic and thrombocytopenicHR-MDS subgroup that showed pathologically increasedresistance to osmotic hemolysis, intracellular calcium (7946±1917 vs. 6026±1541RFU), and metHb/oxyHb ratio (18.5±7.3 vs. 10.4±3.9%), when compared to controls. Of note, similar abnormalities were observed in the EPO subgroup that further showed reticulocytosis, PS externalization, and membrane-bound hemichromes(p&amp;lt;0.05) Compared to the non-treated subgroup, the EPO-LR had lower WBC counts, but higher RDW, PS exposure (0.75±0.44 vs. 0.41±0.26%) and resistance to osmotic stress, aspreviously reported in other EPO-treated patients.Luspatercept-LR had higher WBC and PLT counts but exhibited EPO-like effects on RBCs, including pathological resistance to osmotic/mechanical lysis, ROS concentration (1347±453 vs. 960±160 RFU), Hb oxidation, and PS exposure (1.05±0.60 vs. 0.41±0.26%), compared to the non-treated LR subgroup. Conclusion: MDS RBCs are highly heterogeneous in terms of volume and Hb concentration and present signs of oxidative stress and eryptosis. Consequently, these easily accessible markers could be an accessory tool to the MDS diagnosis.In the context of ineffective hematopoiesis and increased apoptosis of precursor erythroid cells,the LR-MDS patients exhibit minimal RBC abnormalities. On the other hand, the expansion of BM blasts and the lower level of apoptosis in HR-MDS seem to affect RBCs in a hemoglobinopathy-like manner in terms of Hb oxidation, eryptosis signaling, and membrane ion channels. EPO and luspatercept treated LR patients exhibit improved cytopenias but worse RBC physiology most probably attributed to clinical factors like RS phenotype.

Trends and predictions of perioperative transfusion and venous thromboembolism in hepatectomy using a North American Registry.

Studies indicate a link between allogeneic blood transfusion and venous thromboembolism (VTE) post-major surgery. Analyzing trends and predictors of these outcomes after hepatectomy can inform risk management. The American College of Surgeons National Surgical Quality Improvement Program database was used for a retrospective analysis. Primary outcomes were perioperative red blood cell (RBC) transfusion and VTE events within 30 days of hepatectomy. Seven-year trends and predictors were evaluated. Among 29,131 hepatectomy patients, transfusion rates showed no statistically significant decreasing trends (p = .122) from 2014 to 2020 (18.13%-16.71%), while VTE rates showed a downward trend over the 7 years (p = .021); 17.2% received RBC transfusion, with higher rates in surgeries lasting ≥282 min (median: 220 min). Calculated RBC mass [hematocrit (%) × body weight (kg) × 10-5 × 70/ (body mass index/22)] at or below 1.5 L substantially increased transfusion odds. VTE was reported postoperatively in 2.6% of cases more frequently in longer cases involving transfusions. The adjusted odds ratio (aOR) of VTE escalated from the shortest operative time to the longest (3.17; 95% confidence interval [CI], 2.37-4.22). The adjusted odds of VTE doubled for transfused patients compared to non-transfused patients (aOR, 2.19; 95% CI, 1.86-2.57). Rates of RBC transfusion and VTE rates hepatectomy have minimally changed in the recent years. VTE prevention is challenging in extended surgeries at increased risk of bleeding and RBC transfusions. Patient-level data on coagulation and thromboprophylaxis can potentially refine risk assessment for postoperative VTE.

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.