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Annals of Internal Medicine Jul 2012Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American... (Review)
Review
DESCRIPTION
Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.
METHODS
These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).
Topics: Acute Coronary Syndrome; Adult; Blood Banks; Child; Decision Support Techniques; Erythrocyte Transfusion; Guideline Adherence; Hemoglobin A; Hospitalization; Humans; Randomized Controlled Trials as Topic; United States
PubMed: 22751760
DOI: 10.7326/0003-4819-157-1-201206190-00429 -
The Cochrane Database of Systematic... Oct 2016There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients.
OBJECTIVES
The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL).
SEARCH METHODS
We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials.
SELECTION CRITERIA
We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered.
DATA COLLECTION AND ANALYSIS
We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'.
MAIN RESULTS
A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia).
AUTHORS' CONCLUSIONS
Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.
Topics: Anemia; Erythrocyte Transfusion; Hematocrit; Hemoglobin A; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Reference Values; Transplantation, Autologous; Transplantation, Homologous
PubMed: 27731885
DOI: 10.1002/14651858.CD002042.pub4 -
The Lancet. Healthy Longevity Jul 2023Metformin, a first-line medication for type 2 diabetes, might also have a protective effect against ageing-related diseases, but so far little experimental evidence is...
BACKGROUND
Metformin, a first-line medication for type 2 diabetes, might also have a protective effect against ageing-related diseases, but so far little experimental evidence is available. We sought to assess the target-specific effect of metformin on biomarkers of ageing in the UK Biobank.
METHODS
In this drug target mendelian randomisation study, we assessed the target-specific effect of four putative targets of metformin (AMPK, ETFDH, GPD1, and PEN2), involving ten genes. Genetic variants with evidence of causation of gene expression, glycated haemoglobin A (HbA), and colocalisation were used as instruments mimicking the target-specific effect of metformin via HbA lowering. The biomarkers of ageing considered were phenotypic age (PhenoAge) and leukocyte telomere length. To triangulate the evidence, we also assessed the effect of HbA on the outcomes using a polygenic mendelian randomisation design and assessed the effect of metformin use on these outcomes using a cross-sectional observational design.
FINDINGS
GPD1-induced HbA lowering was associated with younger PhenoAge (β -5·26, 95% CI -6·69 to -3·83) and longer leukocyte telomere length (β 0·28, 0·03 to 0·53), and AMPKγ2 (PRKAG2)-induced HbA lowering was associated with younger PhenoAge (β -4·88, -7·14 to -2·62) but not with longer leukocyte telomere length. Genetically predicted HbA lowering was associated with younger PhenoAge (β -0·96 per SD lowering of HbA, 95% CI -1·19 to -0·74) but not associated with leukocyte telomere length. In the propensity score matched analysis, metformin use was associated with younger PhenoAge (β -0·36, 95% CI -0·59 to -0·13) but not with leukocyte telomere length.
INTERPRETATION
This study provides genetic validation evidence that metformin might promote healthy ageing via targets GPD1 and AMPKγ2 (PRKAG2), and the effect could be in part due to its glycaemic property. Our findings support further clinical research into metformin and longevity.
FUNDING
Healthy Longevity Catalyst Award, National Academy of Medicine, and Seed Fund for Basic Research, The University of Hong Kong.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Biological Specimen Banks; Cross-Sectional Studies; Biomarkers; Hemoglobin A; Transcription Factors; Telomere; United Kingdom
PubMed: 37421961
DOI: 10.1016/S2666-7568(23)00085-5 -
The New England Journal of Medicine Mar 2017Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this...
Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).
Topics: Adolescent; Anemia, Sickle Cell; Clinical Trials as Topic; Gene Expression; Genetic Therapy; Genetic Vectors; Hemoglobin A; Humans; Lentivirus; Male; beta-Globins
PubMed: 28249145
DOI: 10.1056/NEJMoa1609677 -
JAMA Jun 2017Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.
IMPORTANCE
Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated.
OBJECTIVE
To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA.
DESIGN, SETTING, AND PARTICIPANTS
Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016.
INTERVENTIONS
Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks.
MAIN OUTCOMES AND MEASURES
Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 μg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects.
RESULTS
Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P < .001) with ferrous sulfate. Mean total iron-binding capacity decreased from 501 to 389 μg/dL (ferrous sulfate) vs 506 to 417 μg/dL (iron complex) (a greater difference of -50 μg/dL [95% CI, -86 to -14 μg/dL] with ferrous sulfate; P < .001). There were more reports of diarrhea in the iron complex group than in the ferrous sulfate group (58% vs 35%, respectively; P = .04).
CONCLUSIONS AND RELEVANCE
Among infants and children aged 9 to 48 months with nutritional iron-deficiency anemia, ferrous sulfate compared with iron polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01904864.
Topics: Anemia, Iron-Deficiency; Child Nutrition Disorders; Child, Preschool; Double-Blind Method; Female; Ferritins; Ferrous Compounds; Hemoglobin A; Humans; Infant; Iron; Iron Compounds; Lost to Follow-Up; Male; Medication Adherence; Polysaccharides; Treatment Outcome
PubMed: 28609534
DOI: 10.1001/jama.2017.6846 -
Bioscience Reports Jan 2019: Hemoglobin (Hb) A, a biochemical marker widely used in monitoring diabetes mellitus, can be quantitatively measured by various examining systems. However, significant...
: Hemoglobin (Hb) A, a biochemical marker widely used in monitoring diabetes mellitus, can be quantitatively measured by various examining systems. However, significant errors still exist. In the present study, we evaluated the HbA level in five patients with compound heterozygotes by five different examining systems and our goal is to identify the existence of erroneous HbA measurement. Blood samples collected from normal (no hemoglobin variants) and abnormal (compound heterozygotes) patients were analyzed by capillary electrophoresis technique and sequence analysis. The samples without HbA expression via above methods were further analyzed for HbA by ion exchange HPLC Variant II/ Variant II Turbo 2.0 (VII and VII-T 2.0), boronate affinity HPLC, capillary electrophoresis, and Tinaquant immunoassay. HbA expression were unexpectedly detected in the compound heterozygous samples by using additional examining systems: The HPLC VII and VII-T 2.0 detected HbA expression in two of five samples and failed to detect the abnormal HbA expression; the CE system detected HbA expression in one of five samples with abnormal HbA expression; the Ultra2 and PPI system detected the HbA expression of all samples without abnormal HbA Five human samples without HbA expression were additionally detected with HbA expression with or without abnormal HbA expression by five analysis systems and the different examining assay potentially affected the test results. These results demonstrated that the limitations of current examining systems for monitoring patients with hemoglobin disorders highlighting the further improvement in the method of clinical HbA examination.
Topics: Blood Chemical Analysis; Electrophoresis, Capillary; Glycated Hemoglobin; Hemoglobin A; Heterozygote; Humans
PubMed: 29720428
DOI: 10.1042/BSR20180128 -
Magnetic Resonance in Medicine Jun 2021Sickle cell anemia is a blood disorder that alters the morphology and the oxygen affinity of the red blood cells. Cerebral oxygen extraction fraction measurements using...
PURPOSE
Sickle cell anemia is a blood disorder that alters the morphology and the oxygen affinity of the red blood cells. Cerebral oxygen extraction fraction measurements using quantitative BOLD contrast have been used for assessing inadequate oxygen delivery and the subsequent risk of ischemic stroke in sickle cell anemia. The BOLD signal in MRI studies relies on , the bulk volume susceptibility difference between fully oxygenated and fully deoxygenated blood. Several studies have measured for normal hemoglobin A (HbA). However, it is not known whether the value is different for sickle hemoglobin. In this study, was measured for both HbA and sickle hemoglobin.
METHODS
Six sickle cell anemia patients and 6 controls were recruited. Various blood oxygenation levels were achieved through in vivo manipulations to keep the blood close to its natural state. To account for the differences in oxygen affinity, Hill's equations were used to translate partial pressure of oxygen to oxygen saturation for HbA, sickle hemoglobin, and fetal hemoglobin (HbF) separately. The pH and PCO corrections were performed. Temperature and magnetic field drift were controlled for. A multivariate generalized linear mixed model with random participant effect was used.
RESULTS
Assuming that is similar for HbA and HbF and that is 5/4 of for HbA, it was found that the values for HbA and sickle hemoglobin were not statistically significantly different from each other.
CONCLUSION
The same value can be used for both types of hemoglobin in quantitative BOLD analysis.
Topics: Hemoglobin A; Hemoglobin, Sickle; Hemoglobins; Humans; Oxygen; Oxyhemoglobins
PubMed: 33475200
DOI: 10.1002/mrm.28668 -
The Cochrane Database of Systematic... Jan 2015Anaemia is a global public health problem. Children under five years of age living in developing countries (mostly Africa and South-East Asia) are highly affected.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anaemia is a global public health problem. Children under five years of age living in developing countries (mostly Africa and South-East Asia) are highly affected. Although the causes for anaemia are multifactorial, malaria has been linked to anaemia in children living in malaria-endemic areas. Administering intermittent preventive antimalarial treatment (IPT) to children might reduce anaemia, since it could protect children from new Plasmodium parasite infection (the parasites that cause malaria) and allow their haemoglobin levels to recover.
OBJECTIVES
To assess the effect of IPT for children with anaemia living in malaria-endemic areas.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Central of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; and LILACS. We also searched the World Health Organization (WHO) International Clinical Trial Registry Platform and metaRegister of Controlled Trials (mRCT) for ongoing trials up to 4 December 2014.
SELECTION CRITERIA
Randomized controlled trials (RCTs) evaluating the effect of IPT on children with anaemia.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias. We analysed data by conducting meta-analyses, stratifying data according to whether participants received iron supplements or not. We used GRADE to assess the quality of evidence.
MAIN RESULTS
Six trials with 3847 participants met our inclusion criteria. Trials were conducted in areas of low malaria endemicity (three trials), and moderate to high endemicity (three trials). Four trials were in areas of seasonal malaria transmission. Iron was given to all children in two trials, and evaluated in a factorial design in a further two trials.IPT for children with anaemia probably has little or no effect on the proportion anaemic at 12 weeks follow-up (four trials, 2237 participants, (moderate quality evidence).IPT in anaemic children probably increases the mean change in haemoglobin levels from baseline to follow-up at 12 weeks on average by 0.32 g/dL (MD 0.32, 95% CI 0.19 to 0.45; four trials, 1672 participants, moderate quality evidence); and may improve haemoglobin levels at 12 weeks (MD 0.35, 95% CI 0.06 to 0.64; four trials, 1672 participants, low quality evidence). For both of these outcomes, subgroup analysis did not demonstrate a difference between children receiving iron and those that did not.IPT for children with anaemia probably has little or no effect on mortality or hospital admissions at six months (three trials, 3160 participants moderate quality evidence). Subgroup analysis did not show a difference between those children receiving iron supplements and those that did not.
AUTHORS' CONCLUSIONS
Trials did show a small effect on average haemoglobin levels but this did not appear to translate into an effect on mortality and hospital admissions. Three of the six trials were conducted in low endemicity areas where transmission is low and thus any protective effect is likely to be modest.
Topics: Anemia; Antimalarials; Child, Preschool; Endemic Diseases; Hemoglobin A; Humans; Infant; Infant, Newborn; Iron Compounds; Malaria; Randomized Controlled Trials as Topic
PubMed: 25582096
DOI: 10.1002/14651858.CD010767.pub2 -
Hematology/oncology Clinics of North... Dec 2010Erythrocytes must regulate hemoglobin synthesis to limit the toxicities of unstable free globin chain subunits. This regulation is particularly relevant in... (Review)
Review
Erythrocytes must regulate hemoglobin synthesis to limit the toxicities of unstable free globin chain subunits. This regulation is particularly relevant in β-thalassemia, in which β-globin deficiency causes accumulation of free α-globin, which forms intracellular precipitates that destroy erythroid precursors. Experimental evidence accumulated over more than 40 years indicates that erythroid cells can neutralize moderate amounts of free α-globin through generalized protein quality control mechanisms, including molecular chaperones, the ubiquitin-proteasome system, and autophagy. In many ways, β-thalassemia resembles protein aggregation disorders of the nervous system, liver, and other tissues, which occur when levels of unstable proteins overwhelm cellular compensatory mechanisms. Information gained from studies of nonerythroid protein aggregation disorders may be exploited to further understand and perhaps treat β-thalassemia.
Topics: Erythrocytes; Erythropoiesis; Hemoglobin A; Humans; Models, Biological; Proteasome Endopeptidase Complex; Ubiquitination; alpha-Globins; beta-Globins; beta-Thalassemia
PubMed: 21075281
DOI: 10.1016/j.hoc.2010.08.013 -
High Altitude Medicine & Biology Jun 2015Simonson, Tatum S. Altitude adaptation: A glimpse through various lenses. High Alt Med Biol 16:125-137, 2015.--Recent availability of genome-wide data from highland... (Review)
Review
Simonson, Tatum S. Altitude adaptation: A glimpse through various lenses. High Alt Med Biol 16:125-137, 2015.--Recent availability of genome-wide data from highland populations has enabled the identification of adaptive genomic signals. Some of the genomic signals reported thus far among Tibetan, Andean, and Ethiopian are the same, while others appear unique to each population. These genomic findings parallel observations conveyed by decades of physiological research: different continental populations, resident at high altitude for hundreds of generations, exhibit a distinct composite of traits at altitude. The most commonly reported signatures of selection emanate from genomic segments containing hypoxia-inducible factor (HIF) pathway genes. Corroborative evidence for adaptive significance stems from associations between putatively adaptive gene copies and sea-level ranges of hemoglobin concentration in Tibetan and Amhara Ethiopians, birth weights and metabolic factors in Andeans and Tibetans, maternal uterine artery diameter in Andeans, and protection from chronic mountain sickness in Andean males at altitude. While limited reports provide mechanistic insights thus far, efforts to identify and link precise genetic variants to molecular, physiological, and developmental functions are underway, and progress on the genomics front continues to provide unprecedented movement towards these goals. This combination of multiple perspectives is necessary to maximize our understanding of orchestrated biological and evolutionary processes in native highland populations, which will advance our understanding of both adaptive and non-adaptive responses to hypoxia.
Topics: Adaptation, Biological; Altitude; Altitude Sickness; Biological Evolution; Ethiopia; Female; Hemoglobin A; Humans; Hypoxia-Inducible Factor 1; Male; South America; Tibet
PubMed: 26070057
DOI: 10.1089/ham.2015.0033