Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although it is almost certain that alpha(+)-thalassemia protects against malaria, the mechanisms for that are still unknown. It has been suggested that an increased number of young circulating red blood cells in alpha(+)-thalassemic children, as a result of some degree of ineffective erythropoiesis, could be related to the high frequencies of the alpha(+)-thalassemic allele in malaria endemic areas. Reticulocyte evaluation in this condition, however, has been poorly performed so far. Our objective was to determine the reticulocyte number and maturation degree, in addition to the soluble transferrin receptor and serum erythropoietin levels, in alpha(+)-thalassemia heterozygotes, comparing them with normal alpha-genotype controls. One hundred twenty-one alpha(+)-thalassemia carriers (-alpha(3.7)/alphaalpha) and 249 controls (alphaalpha/alphaalpha), all of them with normal serum ferritin levels, were subclassified according to age (1-5, 6-10, 11-15, 16-20, and over 20 years old). Reticulocyte analyzes were carried out by flow cytometry and sTfR and s-Epo levels determined by immunonephelometry and chemiluminescence, respectively. The comparisons did not show any significant difference between thalassemics and controls regarding the reticulocyte parameters [percentages and absolute values, P = 0.2643 and 0.5421; high, medium, and low maturation degree, P = 0.2579, 0.2196, and 0.4192; RET maturity index (RMI), P = 0.2471, respectively], as well as the s-Epo levels (P = 0.5711). The sTfR concentrations were higher in the thalassemic group (P = 0.0001), but statistical significance was due only to the 1-5 and over 20 subgroups (P = 0.0082 and 0.0436, respectively). The results found here are compatible with a compensated erythropoiesis and do not confirm the hypothesis mentioned above.
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PMID:Reticulocyte evaluation in alpha(+)-thalassemia. 1636 54

Increased marrow erythropoiesis in patients with thalassemia syndromes results in the expansion of bone marrow cavities and consequently decreases bone tissues, leading to osteoporosis. Whether the soluble transferrin receptor (sTfR), a marker of erythropoietic activity, correlates with the bone mineral density (BMD) in thalassemic patients has not previously been addressed. Forty-six children and adolescents with thalassemia syndromes, who were either not transfused or suboptimally transfused, were studied. BMD was determined by dual-energy X-ray absorptiometry. Blood samples were obtained in order to determine sTfR and hemoglobin. The patients were categorized into four groups: 1, beta-thalassemia/hemoglobin E (beta-thal/E) with transfusion-dependency (TD) (n = 18); 2, beta-thal/E with transfusion-independency (TI) (n = 15); 3, beta-thalassemia major (beta-major) (n = 6); 4, hemoglobin H (HbH) (n = 7). All patients had normal serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH), and intact parathyroid hormone (PTH), serum calcium (Ca), phosphate (P), and 25-OH-vitamin D levels. The BMD of patients in the beta-major and beta-thal/E with TD groups were not significantly different. In comparison with the beta-major and beta-thal/E with TD groups, the beta-thal/E with TI and HbH groups had significantly higher BMD of the total body (TB), femoral neck (FN), and lumbar spine (LS), as well as higher levels of hemoglobin. In contrast, the sTfR levels of the beta-major, beta-thal/E with TI, and HbH groups were significantly lower than those of the beta-thal/E with TD group. The BMD of TB, FN, and LS was negatively correlated with the sTfR level, but positively correlated with the hemoglobin level. In conclusion, increased marrow erythropoiesis is one of the major determinants of reduced bone mass in thalassemic patients with either no transfusion or suboptimal transfusion.
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PMID:Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. 1650 22

Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.
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PMID:The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. 1676 73

Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.
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PMID:Hypocholesterolemia in chronic anemias with increased erythropoietic activity. 1703 15

The erythroid response to acute anemia relies on the rapid expansion in the spleen of a specialized population of erythroid progenitors termed stress BFU-E. This expansion requires BMP4/Madh5-dependent signaling in vivo; however, in vitro, BMP4 alone cannot recapitulate the expansion of stress BFU-E observed in vivo, which suggests that other signals are required. In this report we show that mutation of the Kit receptor results in a severe defect in the expansion of stress BFU-E, indicating a role for the Kit/SCF signaling pathway in stress erythropoiesis. In vitro analysis showed that BMP4 and SCF are necessary for the expansion of stress BFU-E, but only when spleen cells were cultured in BMP4 + SCF at low-oxygen concentrations did we recapitulate the expansion of stress BFU-E observed in vivo. Culturing spleen cells in BMP4, SCF under hypoxic conditions resulted in the preferential expansion of erythroid progenitors characterized by the expression of Kit, CD71, and TER119. This expression pattern is also seen in stress erythroid progenitors isolated from patients with sickle cell anemia and patients with beta-thalassemia. Taken together these data demonstrate that SCF and hypoxia synergize with BMP4 to promote the expansion and differentiation of stress BFU-E during the recovery from acute anemia.
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PMID:BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors. 1728 34

Several studies have provided reference ranges for the concentration of serum transferrin receptor (sTfR) in various white populations, but there is a dearth of relevant reference sTfR data in non-whites. The aim of this investigation was to establish sTfR reference ranges and mean values for a healthy non-white Arab population that could be used also for Arabs worldwide. sTfR and serum ferritin concentrations were estimated by immunoassays and blood counts were determined by conventional methods. Analysis of the data of 114 volunteer Arab blood donors (91 male, 23 female) revealed a higher mean sTfR concentration in males of 22.6+/-8.1 nmol/L (range 10.9-38.7 nmol/L) compared to that in females of 18.7+/-4.4 nmol/L (range 10.7-25.8 nmol/L, p=0.001). There was no significant correlation of sTfR concentration with age, serum ferritin level, or blood haemoglobin level, but a strong inverse correlation was demonstrated with mean cell volume and mean cell haemoglobin of red cells. Iron-replete volunteer subjects with alpha-thalassaemia trait appear to have relatively high mean sTfR concentration. We recommend the use of gender-dependent sTfR reference values for Arabs.
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PMID:Serum transferrin receptor status of healthy adult Arabs. 1731 70

The prevalence of iron deficiency anemia is 2 percent in adult men, 9 to 12 percent in non-Hispanic white women, and nearly 20 percent in black and Mexican-American women. Nine percent of patients older than 65 years with iron deficiency anemia have a gastrointestinal cancer when evaluated. The U.S. Preventive Services Task Force currently recommends screening for iron deficiency anemia in pregnant women but not in other groups. Routine iron supplementation is recommended for high-risk infants six to 12 months of age. Iron deficiency anemia is classically described as a microcytic anemia. The differential diagnosis includes thalassemia, sideroblastic anemias, some types of anemia of chronic disease, and lead poisoning. Serum ferritin is the preferred initial diagnostic test. Total iron-binding capacity, transferrin saturation, serum iron, and serum transferrin receptor levels may be helpful if the ferritin level is between 46 and 99 ng per mL (46 and 99 mcg per L); bone marrow biopsy may be necessary in these patients for a definitive diagnosis. In children, adolescents, and women of reproductive age, a trial of iron is a reasonable approach if the review of symptoms, history, and physical examination are negative; however, the hemoglobin should be checked at one month. If there is not a 1 to 2 g per dL (10 to 20 g per L) increase in the hemoglobin level in that time, possibilities include malabsorption of oral iron, continued bleeding, or unknown lesion. For other patients, an endoscopic evaluation is recommended beginning with colonoscopy if the patient is older than 50.
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PMID:Iron deficiency anemia. 1972 82

Increased fetal hemoglobin (HbF) in erythroid precursors of patients with beta-hemoglobinopathies (sickle cell anemia and beta-thalassemia), in which adult hemoglobin synthesis is defective, ameliorates the clinical symptoms of the underlying diseases. The production of erythroid precursors depends on the action of erythropoietin (EPO), which prevents their apoptosis and stimulates their proliferation. EPO binds to its surface receptor, induces its homodimerization, and initiates a cascade of phosphorylation and dephosphorylation of a series of proteins by kinases and phosphatases, respectively. Vanadate inhibits various phosphatases, including those that are involved in the EPO pathway, thereby intensifying the signal. In this study, we investigated the effect of vanadate on the proliferation and maturation of human erythroid precursors in culture. When vanadate was added to cells derived from normal donors, cell maturation was delayed, as indicated by cell morphology, cell growth kinetics, the rate of appearance of hemoglobin-containing cells, and the expression of surface antigens (CD117, CD71, and glycophorin A). Analysis by high-performance liquid chromatography and flow cytometry of the hemoglobin profile of vanadate-treated normal cells revealed a higher proportion of HbF than was found in untreated cells. When vanadate was added to cells derived from patients with beta-thalassemia, a significant increase in HbF was observed. The results suggest that intensification of the EPO signal by vanadate results in maturation arrest and increased HbF production. Thus, inhibitors that are more specific and less toxic than vanadate may present a novel option for elevating HbF in patients with beta-hemoglobinopathies, as well as for intensifying the EPO response in other forms of anemia.
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PMID:Vanadate elevates fetal hemoglobin in human erythroid precursors by inhibiting cell maturation. 1746 62

Hypertransfusional (>8 transfusions/year) iron in liver biopsies collected immediately after transfusions in beta-thalassemia and sickle cell disease correlated with increased expression (RNA) for iron regulatory proteins 1 and 2 (3-, 9- to 11-fold) and hepcidin RNA: (5- to 8-fold) (each p <.01), while ferritin H and L RNA remained constant. A different H:L ferritin ratio in RNA (0.03) and protein (0.2-0.6) indicated disease-specific trends and suggests novel post-transcriptional effects. Increased iron regulatory proteins could stabilize the transferrin receptor mRNA and, thereby, iron uptake. Increased hepcidin, after correction of anemia by transfusion, likely reflects excess liver iron. Finally, the absence of a detectable change in ferritin mRNA indicates insufficient oxidative stress to significantly activate MARE/ARE promoters.
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PMID:Iron homeostasis during transfusional iron overload in beta-thalassemia and sickle cell disease: changes in iron regulatory protein, hepcidin, and ferritin expression. 1761 66

In thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism. To test this hypothesis, we examined erythroblast transcriptome profiles from 15 healthy, nonthalassemic donors. Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, showed increased expression and secretion during erythroblast maturation. Healthy volunteers had mean GDF15 serum concentrations of 450 +/- 50 pg/ml. In comparison, individuals with beta-thalassemia syndromes had elevated GDF15 serum levels (mean 66,000 +/- 9,600 pg/ml; range 4,800-248,000 pg/ml; P < 0.05) that were positively correlated with the levels of soluble transferrin receptor, erythropoietin and ferritin. Serum from thalassemia patients suppressed hepcidin mRNA expression in primary human hepatocytes, and depletion of GDF15 reversed hepcidin suppression. These results suggest that GDF15 overexpression arising from an expanded erythroid compartment contributes to iron overload in thalassemia syndromes by inhibiting hepcidin expression.
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PMID:High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. 1782 18


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