ascorbic-acid and Thalassemia

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.

Topics: Anemia; Anemia, Sickle Cell; Animals; Antioxidants; Ascorbic Acid; Glucosephosphate Dehydrogenase Deficiency; Humans; Nutrition Disorders; Oxidative Stress; Thalassemia; Vitamin E

Topics: Ascorbic Acid; Blood Transfusion; Humans; Iron; Nutritional Requirements; Thalassemia

This paper reviews the factors governing the rate of iron loading and iron toxicity in the thalassaemia syndromes and sickle cell disease. It outlines the main determinants of iron mobilization by the iron-chelating drug, desferrioxamine, together with the effects of this drug in clinical practice.

Topics: Anemia, Sickle Cell; Ascorbic Acid; Deferoxamine; Drug Administration Schedule; Forecasting; Humans; Iron; Iron Chelating Agents; Sickle Cell Trait; Thalassemia

Topics: Adolescent; Arrhythmias, Cardiac; Ascorbic Acid; Blood Transfusion; Child; Cholelithiasis; Deferoxamine; Endocrine System Diseases; Female; Folic Acid; Growth Disorders; Heart Failure; Hematopoiesis; Humans; Iron; Leg Ulcer; Liver Diseases; Male; Pericarditis; Splenectomy; Thalassemia; Vitamin E

Topics: Ascorbic Acid; Blood Transfusion; Deferoxamine; Endocrine Glands; Heart; Humans; Infusions, Parenteral; Iron; Iron Chelating Agents; Liver; Stroke Volume; Thalassemia

Topics: Adult; Animals; Ascorbic Acid; Deferoxamine; Ferritins; Guinea Pigs; Haplorhini; Hemochromatosis; Hemosiderin; Humans; Iron; Iron Chelating Agents; Liver; Male; Rats; Scurvy; Spleen; Thalassemia

Haemosiderosis is the most common cause of death in patients with thalassaemia major because of haemolysis and the necessary repeated transfusions. It is possible to reduce the lethal iron burden by means of iron-chelating agents. We combine a two-day-high-transfusion-regimen of packed cells with the application of high doses of desferrioxamine (500 mg/kg body weight) intravenously. This way we achieve good iron elimination with minimal psychological stress situations.

Topics: Ascorbic Acid; Blood Transfusion; Child; Deferoxamine; Female; Germany, West; Greece; Hemosiderosis; Humans; Male; Thalassemia; Trace Elements; Turkey

Topics: Adolescent; Adult; Aged; Anemia; Ascorbic Acid; Deferoxamine; Drug Evaluation; Feces; Humans; Iron; Leukocytes; Thalassemia

Erythrocytes from sickle cell anaemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells. Oxidative stress seems to primarily affect the membrane and results in haemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants. To evaluate the impact of vitamins C (VitC) and E (VitE) supplementation in SCA patients, patients over 18 years were randomly assigned to receive VitC 1400 mg + VitE 800 mg per day or placebo orally for 180 d. Eighty-three patients were enrolled (44 vitamins, 39 placebo), median age 27 (18-68) years, 64% female. There were no significant differences between the two groups regarding clinical complications or baseline laboratorial tests. Sixty percent of the patients were VitC deficient, 70% were VitE deficient. Supplementation significantly increased serum VitC and E. However, no significant changes in haemoglobin levels were observed, and, unexpectedly, there was a significant increase in haemolytic markers with vitamin supplementation. In conclusion, VitC + VitE supplementation did not improve anaemia and, surprisingly, increased markers of haemolysis in patients with SCA and S-β(0) -thalassaemia. The exact mechanisms to explain this findings and their clinical significance remain to be determined.

Topics: Adolescent; Adult; Aged; Anemia, Sickle Cell; Antioxidants; Ascorbic Acid; Biomarkers; Dietary Supplements; Double-Blind Method; Drug Utilization; Female; Hemolysis; Hospitalization; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Quality of Life; Reactive Oxygen Species; Sickle Cell Trait; Thalassemia; Vitamin E; Young Adult

The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective doses suggest that it should be developed quickly and thoroughly tested for the management of transfusional iron overload.

Topics: Administration, Oral; Adolescent; Adult; Aged; Ascorbic Acid; Clinical Trials as Topic; Deferiprone; Deferoxamine; Drug Therapy, Combination; Female; Humans; Iron; Iron Chelating Agents; Male; Middle Aged; Neural Tube Defects; Pyridones; Thalassemia

The authors examined the ability of antioxidants to prevent in vitro oxidant damage to the sickle red blood cell (RBC). One millimolar ascorbic acid and alpha-mercaptopropionylglycine significantly (p less than 0.005) protected against RBC Heinz body formation during incubation with acetylphenylhydrazine, while cysteine, cysteamine, and methionine did not. The effect of ascorbic acid was concentration dependent with concentrations as low as 0.1 mM having significant antioxidant effects. Ascorbic acid protected the RBC against hydrogen peroxide induced hemolysis as well (p less than 0.05). Ascorbic acid had a significant stimulatory effect on the rate of glucose oxidation by the pentose phosphate shunt (PPS), especially in the sickle RBC. Ascorbic acid did not protect the RBC from a patient with chronic hemolytic anemia due to G6PDTorrance from Heinz body formation, suggesting that an intact PPS is necessary for ascorbic acid to express its antioxidant properties. These data suggest that clinical trials should be undertaken to examine the efficacy of ascorbic acid in the treatment of SCD.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Anemia, Sickle Cell; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Drug Evaluation; Erythrocytes; Erythrocytes, Abnormal; Heinz Bodies; Humans; In Vitro Techniques; Pentose Phosphate Pathway; Phenylhydrazines; Reticulocytes; Thalassemia; Tiopronin; Vitamin E; Vitamin E Deficiency

Eight patients with beta thalassaemia major suffering from leg ulcers, were treated over an 8-week period with 3 g ascorbic acid daily in a controlled double-blind crossover study. The ulcers of all the patients showed a high rate of either complete or partial healing.

Topics: Administration, Oral; Adolescent; Adult; Ascorbic Acid; Clinical Trials as Topic; Female; Humans; Leg Ulcer; Male; Pilot Projects; Placebos; Thalassemia

A 23-year-old man with a diagnosis of thalassaemia major on regular blood transfusions presented with complaints of intermittent gum bleeds, joint pain, palpable purpura and ecchymoses in both lower limbs, which was confirmed to be scurvy. He improved dramatically with vitamin C supplementation.

Topics: Ascorbic Acid; Diet; Dietary Supplements; Erythrocyte Transfusion; Humans; Male; Scurvy; Thalassemia; Young Adult

Phosphatidylserine (PS), which is normally localized in the cytoplasmic leaflet of the membrane, undergoes externalization during aging or trauma of red blood cells (RBCS: ). A fraction of this PS is shed into the extracellular milieu. Both PS externalization and shedding are modulated by the oxidative state of the cells. In the present study we investigated the effect of calcium (Ca) flux on oxidative stress-induced membrane distribution of PS and its shedding and on the membrane composition and functions. Normal human RBCs were treated with the oxidant t-butyl hydroperoxide, and thalassemic RBCs, which are under oxidative stress, were treated with the antioxidant vitamin C or N-acetylcystein. The intracellular Ca content was modulated by the Ca ionophore A23187 and by varying the Ca concentration in the medium. Ca flux was measured by Fluo-3, PS externalization and shedding were measured by quantitative flow cytometry and membrane composition was measured by (1)H-NMR analysis of the cholesterol and phospholipids. The results indicated that increasing the inward Ca flux induced PS externalization and shedding, which in turn increased the membrane cholesterol/phospholipid ratio and thereby increased the RBC osmotic resistance. In addition, these processes modulated the susceptibility of RBCs to undergo phagocytosis by macrophages; while PS externalization increased phagocytosis, the shed PS prevented it. These results indicate that PS redistribution and shedding from RBCs, which are mediated by increased calcium, have profound effects on the membrane composition and properties and, thus, may control the fate of RBCs under physiological and pathological conditions.

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Calcimycin; Calcium; Cholesterol; Erythrocyte Membrane; Flow Cytometry; Humans; Ionophores; Membrane Lipids; Nuclear Magnetic Resonance, Biomolecular; Osmotic Pressure; Oxidants; Oxidative Stress; Phagocytosis; Phosphatidylserines; Phospholipids; tert-Butylhydroperoxide; Thalassemia

Plasma non-transferrin-bound-iron (NTBI) is believed to be responsible for catalyzing the formation of reactive radicals in the circulation of iron overloaded subjects, resulting in accumulation of oxidation products. We assessed the redox active component of NTBI in the plasma of healthy and beta-thalassemic patients. The labile plasma iron (LPI) was determined with the fluorogenic dihydrorhodamine 123 by monitoring the generation of reactive radicals prompted by ascorbate but blocked by iron chelators. The assay was LPI specific since it was generated by physiologic concentrations of ascorbate, involved no sample manipulation, and was blocked by iron chelators that bind iron selectively. LPI, essentially absent from sera of healthy individuals, was present in those of beta-thalassemia patients at levels (1-16 microM) that correlated significantly with those of NTBI measured as mobilizer-dependent chelatable iron or desferrioxamine chelatable iron. Oral treatment of patients with deferiprone (L1) raised plasma NTBI due to iron mobilization but did not lead to LPI appearance, indicating that L1-chelated iron in plasma was not redox active. Moreover, oral L1 treatment eliminated LPI in patients. The approach enabled the assessment of LPI susceptibility to in vivo or in vitro chelation and the potential of LPI to cause tissue damage, as found in iron overload conditions.

Topics: Ascorbic Acid; Cohort Studies; Humans; Iron; Iron Chelating Agents; Iron Overload; Oxidation-Reduction; Rhodamines; Thalassemia; Transferrin

Topics: Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Humans; Thalassemia

Topics: Administration, Oral; Adolescent; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Drug Therapy, Combination; Humans; Iron; Thalassemia

Topics: Ascorbic Acid; Female; Ferritins; Gene Expression Regulation; Globins; Heterozygote; Humans; Male; Oxidation-Reduction; Thalassemia

Red blood cell (RBC) antioxidant defense was investigated in eight individuals with hemoglobin E (Six EE and two E-B(+) thalassemia) and compared to that in six individuals with thalassemia and ten normal subjects. Individuals with hemoglobin E had increased incubated Heinz body formation (68% +/- 18%; p less than 0.001) compared to normal and thalassemic RBC (10% +/- 2% and 11% +/- 5%, respectively). Stimulated pentose phosphate shunt activity was increased in the thalassemic and decreased in the hemoglobin E RBC as compared to normal. The 2,3-diphosphoglycerate (DPG) content of the EE RBC was increased to 5.59 +/- 0.69 mumol/ml RBC as compared to normal (4.51 +/- 0.77; p less than 0.001). In the EE RBC, there was a direct correlation between Heinz body formation and DPG content (r = 0.73). Ascorbic and dehydroascorbic acid (0.1 and 1.0 mM) were able to decrease the degree of Heinz body formation in the hemoglobin E RBC. Ascorbic acid (0.1 mM) prolonged the response of the pentose shunt. Thus impaired antioxidant defense may account for the persistence of the hemoglobin E gene in areas where malaria is endemic. Oxidant medications should be used with caution in individuals of Southeast Asian origin.

Topics: 2,3-Diphosphoglycerate; Antioxidants; Ascorbic Acid; Diphosphoglyceric Acids; Erythrocytes; Glutathione; Heinz Bodies; Hemoglobin A; Hemoglobin E; Hemoglobins, Abnormal; Humans; Malaria; Pentose Phosphate Pathway; Thalassemia

Topics: Ascorbic Acid; Child; Child, Preschool; Humans; Hydroxyproline; Proline; Thalassemia

The iron chelating ability and potential toxicity of subcutaneous infusions of the calcium and zinc salts of diethylene triamine penta-acetic acid (DTPA) have been assessed in metabolic balance studies in 2 iron-loaded thalassaemic patients. Infusions of calcium DTPA were locally well tolerated and the drug was as effective as desferrioxamine in mobilising iron. However, daily infusions in the 1st patient also produced symptomatic zinc depletion which could not be controlled by simultaneous oral zinc supplements. Zinc DTPA proved ineffective as an iron chelator, but zinc balance could be maintained in the 2nd patient by combining intermittent (every 4 d) use of calcium DTPA with oral zinc supplements. Combined studies with desferrioxamine and calcium DTPA showed the drugs to have additive effects, probably as a result of the chelation of iron from different body sites.

Topics: Administration, Oral; Adult; Ascorbic Acid; Child; Deferoxamine; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Injections, Subcutaneous; Iron; Iron Chelating Agents; Male; Pentetic Acid; Sulfates; Thalassemia; Transfusion Reaction; Zinc; Zinc Sulfate

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Platelets; Child; Child, Preschool; Hemoglobinopathies; Humans; Infant; Iron; Thalassemia

Topics: Ascorbic Acid; Child; Humans; Infant; Iron; Male; Scurvy; Thalassemia

Topics: Ascorbic Acid; Child, Preschool; Ferritins; Humans; Iron; Male; Thalassemia

Topics: Anemia, Hemolytic, Congenital; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Drug Administration Schedule; Humans; Infusions, Parenteral; Iron; Thalassemia; Time Factors

Topics: Adult; Ascorbic Acid; Deferoxamine; Humans; Iron; Thalassemia

The incidence of ascorbic acid (AA) deficiency and its effect on serum ferritin concentration relative to body iron stores was studied in 61 unchelated patients with beta-thalassaemia major. Thirty-nine (64%) of patients had subnormal leucocyte ascorbate concentrations without clinical evidence of scurvy. The lowest leucocyte ascorbate concentrations tended to occur in the most transfused patients. No correlation was found between the units transfused and serum ferritin concentration in the AA-deficient patients but a close correlation (r = +0.82; p less than 0.005) existed for the AA-replete group. Similarly a close correlation (r = +0.77; p less than 0.005) was obtained between liver iron concentration and serum ferritin in AA-replete patients but only a weak correlation (r = +0.385; p less than 0.025) existed for the AA-deficient group. When AA-deficient patients were treated with ascorbic acid, serum iron and percentage saturation of iron binding capacity rose significantly; serum ferritin rose in 13 of 21 patients despite the simultaneous commencement of desferrioxamine therapy. In contrast all three measurements tended to fall in AA-replete patients with ascorbic acid and desferrioxamine therapy. Thus, AA deficiency is commonly present in beta-thalassaemia patients with iron overload and may give rise to inappropriate serum ferritin concentrations in relation to body iron stores.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Female; Ferritins; Humans; Iron; Liver; Male; Thalassemia; Transaminases

Topics: Adult; Ascorbic Acid; Deferoxamine; Dose-Response Relationship, Drug; Feces; Hemosiderosis; Humans; Intestinal Absorption; Iron; Thalassemia; Transfusion Reaction

1. Iron-overloaded spleens from thalassaemic subjects showed a greatly increased susceptibility to free-radical oxidation (peroxidation) in vitro. 2. Iron content was the main but not the only variable governing susceptibility. Added ascorbate had a dose-dependent action either as an antioxidant or as a pro-oxidant, the direction of its effect depending mainly on the degree of iron overload. This has therapeutic implications.

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Edetic Acid; Female; Humans; In Vitro Techniques; Iron; Lipid Peroxides; Male; Spleen; Thalassemia; Vitamin E

Topics: Adolescent; Ascorbic Acid; Blood Transfusion; Child; Deferoxamine; Female; Humans; Iron; Male; Splenectomy; Thalassemia

Topics: Administration, Oral; Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Deferoxamine; Female; Guinea Pigs; Hemosiderosis; Humans; Injections, Subcutaneous; Iron; Male; Scurvy; Thalassemia; Transfusion Reaction

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Iron; Scurvy; Thalassemia; Transfusion Reaction

The status of ascorbic acid was studied at the levels of platelet and leucocyte in 32 cases of iron deficiency anaemia, 35 cases of thalassaemia and 18 normal subjects. It was found that in iron deficiency anaemia, platelet ascorbic acid was significantly higher than normal values indicating tissue excess and came down sharply after treatment with iron. In thalassaemia, associated presumably with iron overload, ascorbic acid status of platelets was definitely lower than normal indicating tissue deficiency. Leucocytic level of ascorbic acid was not as good an index of ascorbic acid status as the platelet level.

Topics: Anemia, Hypochromic; Ascorbic Acid; Blood Platelets; Hemoglobins; Humans; Iron; Leukocytes; Thalassemia; Transferrin

The application of noninvasive techniques to the evaluation of cardiac function in iron overload has identified a high incidence of abnormalities in asymptomatic patients prior to the onset of overt cardiac deterioration. Of the tests we have used, radionuclide cineangiography appears to be the most sensitive because it can be conveniently applied during the physiological stress of exercise. Other tests of cardiac function that include stress are also likely to be more sensitive than resting measurements of cardiac function. Systematic application of these techniques to the study of patients on iron chelation therapy should results in an early determination of the efficacy of such treatment.

Topics: Adolescent; Adult; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Heart; Heart Diseases; Heart Failure; Heart Function Tests; Humans; Iron; Thalassemia; Transfusion Reaction

Topics: Ascorbic Acid; Blood Transfusion; Child; Deferoxamine; Erythrocyte Transfusion; Humans; Iron; Male; Thalassemia

Topics: Adolescent; Ascorbic Acid; Blood Transfusion; Child; Child, Preschool; Deferoxamine; Erythrocyte Transfusion; Humans; Iron; Splenectomy; Thalassemia

A program to train patients with Cooley's anemia to self-administer deferoxamine via an intermittent infusion pump is described. A pharmacist provides the patient and his family with indepth information on the disease and on deferoxamine dosage, preparation, subcutaneous administration, stability, storage, side effects and precautions. Patients are trained by the pharmacist in aseptic technique and in use and maintenance of the intermittent infusion pump. The patient education program allows patients with Cooley's anemia to receive their daily deferoxamine therapy without the neef for frequent hospitalization.

Topics: Ascorbic Acid; Asepsis; Deferoxamine; Drug Therapy, Combination; Evaluation Studies as Topic; Humans; Infusions, Parenteral; Injections, Subcutaneous; New York; Patient Education as Topic; Pharmacy Service, Hospital; Self Administration; Syringes; Thalassemia

Topics: Ascorbic Acid; Blood Transfusion; Deferoxamine; Humans; Splenectomy; Thalassemia

The iron-chelating agent, deferoxamine, was studied in 16 patients with thalassemia major. Urinary excretion of iron in response to 0.75 gm of deferoxamine, intramuscularly, ranged from 2.2 to 44.8 mg Fe/24 hours. In response to a subcutaneous infusion of 1.5 gm deferoxamine for 18 hours, iron excretion increased by an average of 240%. The intravenous infusion of large doses of deferoxamine for 18 hours resulted in the highest rate of iron excretion, as much as 447.5 mg Fe/24 hours in response to 16 gm of deferoxamine. Administration of vitamin C increased chelation-induced excretion of iron in most patients more than five years of age. Preliminary evidence suggests that further iron accumulation can be prevented and excessive iron stores can be depleted by the intramuscular, subcutaneous, or intravenous administration of deferoxamine.

Topics: Adolescent; Adult; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Female; Humans; Infusions, Parenteral; Injections, Intramuscular; Iron; Thalassemia

Topics: Adolescent; Ascorbic Acid; Blood Transfusion; Child; Child, Preschool; Deferoxamine; Erythrocyte Transfusion; Female; Humans; Infusions, Parenteral; Injections, Intramuscular; Iron; Male; Thalassemia

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Deferoxamine; Drug Evaluation; Female; Hemochromatosis; Hemosiderosis; Humans; Iron; Male; Middle Aged; Thalassemia

Topics: Anemia, Sideroblastic; Animals; Ascorbic Acid; Chelating Agents; Deferoxamine; Hemosiderosis; Humans; Iron; Metabolic Diseases; Thalassemia

The effect of 12 and 24 h continuous subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion was compared in 13 patients with beta-thalassaemia major and 1 with congenital sideroblastic anaemia, all of whom were receiving regular blood-transfusions. 750 mg D.F. given over a 12 h period, gave a mean total (30 h) iron excretion of 17-5 mg, which was not statistically different from the mean iron excretion of 21-5 mg when the same dose was delivered over 24 h. 1500 mg D.F. gave a mean urinary iron excretion of 28-1 mg with a 12 h infusion, which was significantly less than the mean iron excretion of 39-6 mg with 24 h infusion. The 1500 mg dose gave a significant increase in iron excretion compared with the 750 mg dose when given by either 12 h or 24 h infusion. 7 of 8 patients, given D.F. over a 12 h period, had increased iron excretion when the dose was increased from 750 to 2000 mg. When the dose was increased to 4000 mg, however, the effect on iron excretion was variable. On the other hand, ascorbic-acid therapy was invariably associated with increased iron excretion after subcutaneous D.F. In twelve studies at different dose levels of D.F., ascorbate therapy was associated with increased iron excretion ranging from 24 to 245%. It is concluded that in most patients with transfusional iron overload subcutaneous D.F over a 12 h period, at a dose ranging from 2 to 4 g daily with ascorbic-acid saturation, is at present the most satisfactory method of removing excess iron.

Topics: Administration, Oral; Adolescent; Adult; Anemia, Sideroblastic; Ascorbic Acid; Child; Deferoxamine; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Hemosiderosis; Humans; Infusions, Parenteral; Iron; Male; Skin; Thalassemia; Transfusion Reaction

Absorption of 59Fe ferrous sulphate was measured in patients with a variety of iron-loading anaemias both before and during subcutaneous infusions of desferrioxamine. The infusions were associated with a reduction in absorption (P less than 0-025). This effect was not altered by saturation with ascorbic acid.

Topics: Administration, Oral; Adolescent; Adult; Anemia, Aplastic; Anemia, Sideroblastic; Ascorbic Acid; Binding Sites; Blood Transfusion; Deferoxamine; Drug Synergism; Erythrocytes; Female; Ferritins; Ferrous Compounds; Humans; Infusions, Parenteral; Intestinal Absorption; Iron; Iron Radioisotopes; Isotope Labeling; Male; Thalassemia

Topics: Adult; Anemia, Sideroblastic; Ascorbic Acid; Deferoxamine; Drug Administration Schedule; Female; Hemosiderosis; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Male; Middle Aged; Primary Myelofibrosis; Thalassemia; Transfusion Reaction

Topics: Adolescent; Adult; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Humans; Hypersplenism; Infant; Iron; Splenectomy; Thalassemia; Transfusion Reaction; United Kingdom

Since deferoxamine B, when administered as a single daily intramuscular injection of 0.75 g, is unable to promote sufficient urinary iron excretion to achieve net negative iron balance in siderosis, we evaluated its administration as a constant infusion over 24 hours. We compared intravenous and subcutaneous routes in 24 siderotic patients who had excreted 420 to 630 mg (mean, 480 mg) of iron per month on intramuscular therapy. With the intravenous route urinary iron excretions increased to 570 to 3690 mg (mean, 1595 mg) per month. Constant subcutaneous delivery was 90 per cent as effective as intravenous administration on a dose-for-dose basis. Noteworthy net cumulative urinary iron excretions (urinary iron excretions minus transfused iron), often in excess of 1 g per month, have been maintained in all patients. Constant subcutaneous deferoxamine administration may prove to be an effective and practical means of eliminating large quantities of iron in siderosis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Humans; Injections, Intramuscular; Injections, Subcutaneous; Iron; Middle Aged; Siderosis; Thalassemia; Time Factors

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Black People; Child; Disease Models, Animal; Guinea Pigs; Hemosiderosis; Humans; Iron; Leukocytes; Liver; Oxalates; South Africa; Thalassemia

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Drug Synergism; Humans; Iron; Thalassemia; Transfusion Reaction

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Cyprus; Deferoxamine; Drug Synergism; Humans; Iron; Liver; Thalassemia; Time Factors; Transfusion Reaction

Topics: Ascorbic Acid; Chelating Agents; Child; Child, Preschool; Deferoxamine; Humans; Intestinal Absorption; Iron; Pentetic Acid; Thalassemia; Transfusion Reaction

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Humans; Injections, Intramuscular; Malabsorption Syndromes; Thalassemia; Time Factors

Studies of the ascorbic acid status in two subjects with idiopathic haemochromatosis and in 12 with transfusional siderosis showed that all had decreased levels of white cell ascorbic acid. The urinary excretion of ascorbic acid was also diminished in those subjects in whom such measurements were made. The administration of ascorbic acid was followed by only a small rise in the urinary ascorbic acid output, while the oxalic acid levels (measured in two subjects) showed a significant rise. These findings resemble those described in siderotic Bantu, and support the thesis that increased iron stores lead to irreversible oxidation of some of the available ascorbic acid.

Topics: Adolescent; Adult; Ascorbic Acid; Blood Platelets; Blood Transfusion; Child; Diet; Hemochromatosis; Humans; Iron; Leukocytes; Middle Aged; Oxalates; Siderosis; Thalassemia

Topics: Anemia; Ascorbic Acid; beta-Thalassemia; Child; Humans; Infant; Plasma; Thalassemia