What are RBC-transfusion-dependence and -independence?
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ABSTRACT:
SUBMITTER: Gale RP
PROVIDER: S-EPMC8215731 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%; P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 109/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.
| S-EPMC5383927 | biostudies-literature
Project description:Incompatible red blood cell (RBC) transfusion can result in life-threatening transfusion complications that can be challenging to manage in patients with transfusion-dependent anemia. However, not all incompatible RBC transfusions result in significant RBC removal. One factor that may regulate the outcome of incompatible RBC transfusion is the density of the incompatible antigen. Despite the potential influence of target antigen levels during incompatible RBC transfusion, a model system capable of defining the role of antigen density in this process has not been developed. In this study, we describe a novel model system of incompatible transfusion using donor mice that express different levels of the KEL antigen and recipients with varying anti-KEL antibody concentrations. Transfusion of KEL+ RBCs that express high or moderate KEL antigen levels results in rapid antibody-mediated RBC clearance. In contrast, relatively little RBC clearance was observed following the transfusion of KEL RBCs that express low KEL antigen levels. Intriguingly, unlike RBC clearance, loss of the KEL antigen from the transfused RBCs occurred at a similar rate regardless of the KEL antigen density following an incompatible transfusion. In addition to antigen density, anti-KEL antibody levels also regulated RBC removal and KEL antigen loss, suggesting that antigen density and antibody levels dictate incompatible RBC transfusion outcomes. These results demonstrate that antibody-induced antigen loss and RBC clearance can occur at distinct antigen density thresholds, providing important insight into factors that may dictate the outcome of an incompatible RBC transfusion.
| S-EPMC7839377 | biostudies-literature
Project description:OBJECTIVES:To determine RBC transfusion practice and relationships between RBC transfusion volume and mortality in infants and children treated with extracorporeal membrane oxygenation. DESIGN:Secondary analysis of a multicenter prospective observational study. SETTING:Eight pediatric institutions within the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Collaborative Pediatric Critical Care Research Network. PATIENTS:Patients age less than 19 years old treated with extracorporeal membrane oxygenation at a participating center. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Clinical data and target hemoglobin or hematocrit values (if set) were recorded daily by trained bedside extracorporeal membrane oxygenation specialists and research coordinators. Laboratory values, including hemoglobin and hematocrit, were recorded daily using the value obtained closest to 8:00 AM. RBC transfusion was recorded as total daily volume in mL/kg. Multivariable logistic regression was used to determine the relationship between RBC transfusion volume and hospital mortality, accounting for potential confounders. Average goal hematocrits varied across the cohort with a range of 27.5-41.3%. Overall, actual average daily hematocrit was 36.8%, and average RBC transfusion volume was 29.4?mL/kg/d (17.4-49.7?mL/kg/d) on extracorporeal membrane oxygenation. On multivariable analysis, each additional 10?mL/kg/d of RBC transfusion volume was independently associated with a 9% increase in odds of hospital mortality (adjusted odds ratio, 1.09 [1.02-1.16]; p = 0.009). CONCLUSIONS:In this multicenter cohort of pediatric extracorporeal membrane oxygenation patients, daily hematocrit levels were maintained at normal or near-normal values and RBC transfusion burden was high. RBC transfusion volume was independently associated with odds of mortality. Future clinical studies to identify optimum RBC transfusion thresholds for pediatric extracorporeal membrane oxygenation are urgently needed.
| S-EPMC6085106 | biostudies-literature
Project description:OBJECTIVES:Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values. DESIGN:Prospective study measuring cerebral blood flow and oxygen extraction fraction using O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5?mL/100?g/min. SETTING:PET facility located within the Neurology/Neurosurgery ICU. PATIENTS:Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7-13?g/dL. INTERVENTIONS:Transfusion of one unit of RBCs over 1 hour. MEASUREMENTS AND MAIN RESULTS:Baseline hemoglobin was 9.7?g/dL (range, 6.9-12.9), and cerebral blood flow was 43?±?11?mL/100?g/min. After transfusion, hemoglobin rose from 9.6?±?1.4 to 10.8?±?1.4?g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4-6.6) to 5.5?mL/100?g/min (interquartile range, 4.8-7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions). CONCLUSIONS:This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that restrictive transfusion practices may not be appropriate in this population. Large prospective trials are necessary to determine if these physiologic benefits translate into clinical improvement and outweigh the risk of transfusion.
| S-EPMC5350019 | biostudies-literature
Project description:BACKGROUND:Exchange transfusion is a mainstay in the treatment of sickle cell anemia. Transfusion recipients with sickle cell disease (SCD) can be transfused over 10 units per therapy, an intervention that replaces circulating sickle red blood cells (RBCs) with donor RBCs. Storage of RBCs makes the intervention logistically feasible. The average storage duration for units transfused at the Duke University Medical Center is approximately 2 weeks, a time window that should anticipate the accumulation of irreversible storage lesion to the RBCs. However, no metabolomics study has been performed to date to investigate the impact of exchange transfusion on recipients' plasma and RBC phenotypes. STUDY DESIGN AND METHODS:Plasma and RBCs were collected from patients with sickle cell anemia before transfusion and within 5 hours after exchange transfusion with up to 11 units, prior to metabolomics analyses. RESULTS:Exchange transfusion significantly decreased plasma levels of markers of systemic hypoxemia like lactate, succinate, sphingosine 1-phosphate, and 2-hydroxyglutarate. These metabolites accumulated in transfused RBCs, suggesting that RBCs may act as scavenger/reservoirs. Transfused RBCs displayed higher glycolysis, total adenylate pools, and 2,3-diphosphoglycerate, consistent with increased capacity to deliver oxygen. Plasma levels of acyl-carnitines and amino acids decreased, while fatty acids and potentially harmful phthalates increased upon exchange transfusion. CONCLUSION:Metabolic phenotypes confirm the benefits of the transfusion therapy in transfusion recipients with SCD and the reversibility of some of the metabolic storage lesion upon transfusion in vivo in 2-week-old RBCs. However, results also suggest that potentially harmful plasticizers are transfused.
| S-EPMC6283695 | biostudies-literature
Project description:Red blood cell (RBC) alloimmunization represents a significant immunological challenge for some patients. While a variety of immune constituents likely contribute to the initiation and orchestration of alloantibodies to RBC antigens, identification of key immune factors that initiate alloantibody formation may aid in the development of a therapeutic modality to minimize or prevent this process. To define the immune factors that may be important in driving alloimmunization to an RBC antigen, we determined the specific immune compartment and distinct cells that may initially engage transfused RBCs and facilitate subsequent alloimmunization. Our findings demonstrate that the splenic compartment is essential for formation of anti-KEL antibodies following KEL RBC transfusion. Within the spleen, transfused KEL RBCs are found within the marginal sinus, where they appear to specifically co-localize with marginal zone (MZ) B cells. Consistent with this, removal of MZ B cells completely prevented alloantibody formation following KEL RBC transfusion. While MZ B cells can mediate a variety of key downstream immune pathways, depletion of follicular B cells or CD4 T cells failed to similarly impact the anti-KEL antibody response, suggesting that MZ B cells may play a key role in the development of anti-KEL IgM and IgG following KEL RBC transfusion. These findings highlight a key contributor to KEL RBC-induced antibody formation, wherein MZ B cells facilitate antibody formation following RBC transfusion.
| S-EPMC6250814 | biostudies-literature
Project description:Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular injury in the distal lung plays a central role in the development of lung injury following blood transfusion. Here we present a novel microengineering strategy to model and investigate this key disease process. Specifically, we created a microdevice for culturing primary human lung endothelial cells under physiological flow conditions to recapitulate the morphology and hemodynamic environment of the pulmonary microvascular endothelium in vivo. Perfusion of the microengineered vessel with human RBCs resulted in abnormal cytoskeletal rearrangement and release of intracellular molecules associated with regulated necrotic cell death, replicating the characteristics of acute endothelial injury in transfused lungs in vivo. Our data also revealed the significant effect of hemodynamic shear stress on RBC-induced microvascular injury. Furthermore, we integrated the microfluidic endothelium with a computer-controlled mechanical stretching system to show that breathing-induced physiological deformation of the pulmonary microvasculature may exacerbate vascular injury during RBC transfusion. Our biomimetic microsystem provides an enabling platform to mechanistically study transfusion-associated pulmonary vascular complications in susceptible patient populations.
| S-EPMC5469736 | biostudies-literature
Project description:The transfusion of stored RBCs decreases nitric oxide bioavailability, which may have an adverse effect on vascular function. We assessed the effects of RBC transfusion on coronary vascular function by evaluating the relationship between myocardial oxygen delivery and demand as evidenced by ST segment variability.DesignRetrospective case-control study.SettingNine-hundred seventy-three-bed pediatric hospital with a 54-bed cardiovascular ICU.PatientsSeventy-three neonates with hypoplastic left heart syndrome following the Norwood procedure, 38 with a Blalock-Taussig shunt and 35 with a right ventricle to pulmonary artery shunt.InterventionsRBC transfusion.Materials and main resultsHigh-frequency physiologic data were captured 30 minutes prior to the initiation of (baseline) and during the 120 minutes of the transfusion. A rate pressure product was calculated for each subject and used as an indicator of myocardial oxygen demand. Electrocardiogram leads (aVL, V1, II) were used to construct a 3D ST segment vector to assess ST segment variability and functioned as a surrogate indicator of myocardial ischemia. One-hundred thirty-eight transfusions occurred in the Blalock-Taussig shunt group and 139 in the right ventricle to pulmonary artery shunt group. There was no significant change in the rate pressure product for either group; however, ST segment variability progressively increased for the entire cohort during the transfusion, becoming statistically significant by the end of the transfusion. Upon subgroup analysis, this finding was noted with statistical significance in the Blalock-Taussig shunt group and trending toward significance in the right ventricle to pulmonary artery shunt group.ConclusionsWe found a significant increase in the ST segment variability and evidence of myocardial ischemia temporally associated with RBC transfusions in neonates following the Norwood procedure, specifically among those in the Blalock-Taussig shunt group, which may impact immediate and long-term outcomes.
| S-EPMC8140762 | biostudies-literature
Project description:Research supports the efficacy and safety of restrictive transfusion protocols to reduce avoidable RBC transfusions, but evidence of their effectiveness in practice is limited. This study assessed whether admission to an ICU with an restrictive transfusion protocol reduces the likelihood of transfusion for adult patients.Observational study using data from the multicenter, cohort Critical Illness Outcomes Study. Patient-level analyses were conducted with RBC transfusion on day of enrollment as the outcome and admission to an ICU with a restrictive transfusion protocol as the exposure of interest. Covariates included demographics, hospital course (e.g., lowest hematocrit, blood loss), severity of illness (e.g., Sequential Organ Failure Assessment score), interventions (e.g., sedation/analgesia), and ICU characteristics (e.g., size). Multivariable logistic regression modeling assessed the independent effects of restrictive transfusion protocols on transfusions.Fifty-nine U.S. ICUs.A total of 6,027 adult ICU patients.None.Of the 59 study ICUs, 24 had an restrictive transfusion protocol; 2,510 patients (41.6%) were in an ICU with an restrictive transfusion protocol. The frequency of RBC transfusion among patients with severe (hematocrit, < 21%), moderate (hematocrit, 21-30%), and mild (hematocrit, > 30%) anemia in restrictive transfusion protocol ICUs was 67%, 19%, and 4%, respectively, compared with 60%, 14%, and 2% for those in ICUs without an restrictive transfusion protocol. Only 27% of transfusions were associated with a hematocrit less than 21%. Adjusting for confounding factors, restrictive transfusion protocols independently reduced the odds of transfusion in moderate anemia with an odds ratio of 0.59 (95% CI, 0.36-0.96) while demonstrating no effect in mild (p = 0.93) or severe (p = 0.52) anemia.In this sample of ICU patients, transfusions often occurred outside evidence-based guidelines, but admission to an ICU with an restrictive transfusion protocol did reduce the risk of transfusion in moderately anemic patients controlling for patient and ICU factors. This study supports the effectiveness of restrictive transfusion protocols for influencing transfusions in clinical practice.
| S-EPMC5547397 | biostudies-literature
Project description:Identifying dependency in multivariate data is a common inference task that arises in numerous applications. However, existing nonparametric independence tests typically require computation that scales at least quadratically with the sample size, making it difficult to apply them in the presence of massive sample sizes. Moreover, resampling is usually necessary to evaluate the statistical significance of the resulting test statistics at finite sample sizes, further worsening the computational burden. We introduce a scalable, resampling-free approach to testing the independence between two random vectors by breaking down the task into simple univariate tests of independence on a collection of 2 × 2 contingency tables constructed through sequential coarse-to-fine discretization of the sample space, transforming the inference task into a multiple testing problem that can be completed with almost linear complexity with respect to the sample size. To address increasing dimensionality, we introduce a coarse-to-fine sequential adaptive procedure that exploits the spatial features of dependency structures. We derive a finite-sample theory that guarantees the inferential validity of our adaptive procedure at any given sample size. We show that our approach can achieve strong control of the level of the testing procedure at any sample size without resampling or asymptotic approximation and establish its large-sample consistency. We demonstrate through an extensive simulation study its substantial computational advantage in comparison to existing approaches while achieving robust statistical power under various dependency scenarios, and illustrate how its divide-and-conquer nature can be exploited to not just test independence, but to learn the nature of the underlying dependency. Finally, we demonstrate the use of our method through analysing a dataset from a flow cytometry experiment.
| S-EPMC9648765 | biostudies-literature