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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-transferrin-bound iron (NTBI), a potentially toxic compound, is increased in the serum of patients with iron overload and fully saturated transferrin. We found markedly elevated NTBI levels in 16 children (including nine with sickle cell disease and five with beta-thalassemia) with iron overload secondary to prolonged transfusion therapy. During iron chelation with subcutaneous desferrioxamine infusion, NTBI levels decreased to normal, but became elevated within 2 to 4 hours after discontinuation of desferrioxamine. NTBI causes hepatic and cardiac toxicity in experimental systems, but our patients lacked sufficient organ dysfunction for this association to be made. The use of continuous 24-hour chelation to maintain NTBI at low levels may prevent progressive iron toxicity in patients who first received chelation therapy at an older age or who already have evidence of cardiac damage.
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PMID:Non-transferrin-bound iron in long-term transfusion in children with congenital anemias. 308 76

Concentration of iron in plasma, total iron-binding capacity (TIBC), and transferrin saturation are often determined by standard spectrophotometric methods, but iron concentration may be quantified by immunoprecipitation or, electrochemically, by controlled-potential coulometry. Because these iron assays do not all measure the same form(s) of iron, we studied subjects in various states of iron nutriture: normal adults, iron-deficient patients, thalassemia patients with unsaturated transferrin or oversaturated transferrin, and patients with idiopathic hemochromatosis. The spectrophotometric and coulometric methods detected essentially all non-heme iron in plasma; results correlated well but showed a negative bias toward the coulometric method. Results by an immunoprecipitation procedure, which measures only transferrin-bound iron, correlated well with those obtained coulometrically but were slightly higher than the latter. The characteristics of the various methods for iron must be understood by the clinical laboratory if diagnosis of iron disorders is to be accurate.
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PMID:Interpreting results of coulometry and immunoprecipitation in diagnosing iron disorders. 329 21

In 33 patients with thalassemia and idiopathic hemochromatosis, plasma ferritin protein levels ranged from 36 to 5,850 micrograms/L. The iron content of this ferritin as determined by immunoprecipitation ranged from undetectable amounts to 507 micrograms/L. The mean iron content of ferritin protein in those and other subjects with plasma ferritin concentrations of over 1,000 was 6.8% +/- 2.7%. Plasma transferrin was usually saturated with iron in patients with measurable ferritin iron, but exceptions occurred. In studies using electrophoretic separation, it was shown that some ferritin iron moved to transferrin during in vitro incubation, whereas exchange in the opposite direction was extremely limited. Because some plasma ferritin iron was measured by the standard colorimetric plasma iron determination, these observations (a) indicate that plasma ferritin contains a significant amount of iron (b) indicate that a significant proportion of nontransferrin iron in individuals with nontransferrin iron as detected by standard plasma iron and total iron-binding capacity measurements is due to the presence of ferritin, and (c) suggest that large amounts of ferritin iron may affect the saturation of plasma transferrin.
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PMID:Quantitation of ferritin iron in plasma, an explanation for non-transferrin iron. 335 90

The adequacy of tissue iron supply was examined with ferrokinetic techniques in subjects with decreased plasma iron concentration and in subjects with a normal plasma iron concentration but with increased tissue iron requirements. The competition by transferrin receptors for diferric vs monoferric transferrin was measured in eight normal persons and eight with iron deficiency. There was a highly significant (P less than 0.001) decrease in receptor preference for diferric transferrin in subjects with iron deficiency, indicating an insufficient amount of iron-bearing transferrin to saturate tissue receptors. The adequacy of the plasma iron supply was also examined by determining the number of iron-bearing transferrin molecules with receptors at normal and elevated plasma iron concentrations. Significant increases were found at the higher plasma iron concentration, not only in patients with iron deficiency, but also in patients with sickle cell anemia and thalassemia. Furthermore, the increase in the latter two groups was shown to be proportional to the degree of erythroid hyperplasia. These data indicate that tissue iron supply must be evaluated in terms of both plasma iron supply and erythropoietic requirements and that a relative iron deficiency is frequent in patients with erythroid hyperplasia.
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PMID:Adequacy of iron supply for erythropoiesis: in vivo observations in humans. 368 Nov 15

Nontransferrin-bound iron (NTBI) was separated from transferrin bound iron (TBI) by DEAE-Sephadex-CDS filtration. TBI is eluted with Tris-NaCl buffer, NTBI that is retained on the column is eluted with citric acid. NTBI was identified in serum from thalassemia and sickle cell patients. Normal serum contained less than 6% NTBI as compared with 15-18% in patient's sera. NTBI levels were decreased significantly after 8 hr chelation with deferoxamine (DFO).
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PMID:Nontransferrin-bound serum iron in thalassemia and sickle cell patients. 379 14

A group of heteroaromatic chelators with an alpha-ketohydroxy binding site have been tested for their ability to mobilise iron from transferrin in vitro. When these chelators were mixed with iron-saturated transferrin at physiological pH, biphasic reactions were observed. The alpha-ketohydroxy heteroaromatic chelators were found to cause substantial iron removal compared to other known chelators. These findings suggest that these chelators may have an important role in the study of iron metabolism and a possible clinical use in the treatment of transfusional iron overload in thalassaemia, and other diseases of iron imbalance.
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PMID:The study of iron mobilisation from transferrin using alpha-ketohydroxy heteroaromatic chelators. 394 57

Serum ferritin, serum iron, and unsaturated iron binding capacity were studied in 64 patients with beta homozygous thalassemia (BHT), 120 patients with beta heterozygous thalassemia, and 46 normal subjects. Incidence of iron overload seen in 32 BHT cases was similar in untransfused and transfused cases. Among heterozygotes, iron stores were depleted in 24 (20%), mostly females (70.8%). Only male heterozygotes but not normals were iron deficient. In 18 (75%) heterozygotes with depleted iron stores, transferrin saturation (TS) was normal. It was also normal in 8 (25%) BHT patients and 5 (100%) heterozygotes with iron overload. In 13 (35.1%) BHT patients, it was raised in the absence of iron overload. It was concluded that iron deficiency in heterozygotes is of greater magnitude, especially in females, than hitherto known in India. Transferrin saturation is not a good indicator of either iron depletion or overload. Iron supplementation is recommended in heterozygous beta thalassemia in infants, children, and expectant mothers in geographic areas with high incidence of iron deficiency.
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PMID:A study of serum ferritin in beta thalassemia. Iron deficiency and overload. 401 70

The diagnostic potential of the combined use of zinc-protoporphyrin (ZPP), mean corpuscular volume (MCV) and haemoglobin measurements for discriminating between iron deficiency anaemia, beta-thalassaemia minor and lead poisoning has been studied. Lead poisoning could be identified by ZPP greater than 50 micrograms/dl in the presence of normal MCV or ZPP greater than 150 micrograms/dl in the presence of microcytosis (MCV less than 80 fl) with a sensitivity of 97% and specificity 94%. Beta-thalassaemia minor was identified by the coexistence of microcytosis and ZPP less than 50 micrograms/dl with a sensitivity of 91% and specificity 79%. Iron deficiency anaemia defined by the combination of microcytosis and ZPP ranging from 50 to 150 micrograms/dl was identified with a sensitivity of 95%, but the specificity was only 51%, with many of the patients overlapping with thalassaemia minor. This problem did not exist in iron-deficiency anaemia with haemoglobin less than 10 g/dl as at that range no patients with uncomplicated thalassaemia minor have been encountered. A great advantage of the combined use of ZPP, MCV and haemoglobin for the initial screening of microcytic anaemia is its ease of performance and low cost. However, this information should only be regarded as presumptive evidence of disease, requiring subsequent confirmation by appropriate direct measurements such as transferrin saturation, serum ferritin, haemoglobin electrophoresis, or blood lead determinations.
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PMID:Combined use of zinc protoporphyrin (ZPP), mean corpuscular volume and haemoglobin measurements for classifying microcytic RBC disorders in children and young adults. 407 41

The transferrin iron transport system, along with its procurement sites and delivery receptors, provides a highly effective means of satisfying internal iron requirements. Iron uptake by individual tissues is determined by their receptor number, by the relative amounts of monoferric and diferric transferrin in circulation, and by the amount of available iron in donor tissues. Although the modus operandi of this system under basal conditions has been characterized, its exquisite regulation remains an enigma. In some manner, the procurement of iron is determined by iron requirements. What seems to be an inappropriate behavior of the absorptive mechanism in thalassemia and certain other erythroid overload states may actually be life-saving in the absence of transfusion, since it results in higher levels of plasma iron and thereby higher levels of erythropoiesis. The definition of the regulatory mechanism in such conditions may well lead to an understanding of the molecular defect in idiopathic hemochromatosis.
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PMID:Transferrin: physiologic behavior and clinical implications. 608 33

In 207 children chemical measurement of total iron binding capacity (TIBC) and direct immunological evaluation of transferrin by radial immunodiffusion were compared. In addition, serum ferritin was measured in nearly all cases, to exclude iron deficiency. In 14 newborns, 20 infants and 35 older children TIBC and transferrin values correlated significantly (p < 0.001), as well as in various disorders (infections, hyporegenerative anemia, beta-thalassemia, acute blood loss) and in prelatent, latent and manifest iron deficiency. Standard deviations of both methods were comparable. Anemia and hyposideremia due to infection could be clearly distinguished from iron deficiency of all stages. The diagnosis of prelatent iron deficiency, however, can be definitely established only by measurement of serum ferritin or other more complicated procedures (59Fe2+-whole body retention test, estimation of diffuse iron in bone marrow macrophages). An interesting finding was the negative significant correlation (r = 0.69) between the two iron binding proteins in serum, transferrin and ferritin. In summary, the simple radial immunodiffusion technique for transferrin with its minimal requirement of serum can be recommended for pediatric routine laboratories in the differential diagnosis of anemia and hyposideremia, before unnecessary iron medication is institued.
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PMID:[Comparison of indirect and direct measurement of transferrin in healthy and sick children (author's transl)]. 610 44


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