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CHAPTER 39 ANEMIA DUE TO OTHER NUTRITIONAL DEFICIENCIES

CHAPTER 39 ANEMIA DUE TO OTHER NUTRITIONAL DEFICIENCIES
Williams Hematology

CHAPTER 39 ANEMIA DUE TO OTHER NUTRITIONAL DEFICIENCIES

ERNEST BEUTLER

Vitamin-Deficiency Anemias

Vitamin A Deficiency

Deficiencies of Members of the Vitamin B Group

Vitamin C (Ascorbic Acid) Deficiency

Vitamin E Deficiency
Trace Metal Deficiency

Copper Deficiency

Zinc Deficiency

Selenium Deficiency
Anemia of Starvation
Anemia of Protein Deficiency (Kwashiorkor)
Alcoholism
Chapter References

Anemia may result from nutritional deficiencies of a variety of vitamins and trace minerals. Vitamin deficiencies that have been implicated as causes of anemia in humans, in addition to folic acid and vitamin B12, include vitamins A, C, and E, pyridoxine and riboflavin, members of the B group. In most instances the relationship between the hematologic abnormality and deficiency of a vitamin has been difficult to document in humans, since multiple defects are usually present in a clinical setting. Copper, as well as iron, is recognized as a mineral essential for optimal erythropoiesis; a number of different enzymes essential in the metabolism of iron are cuproenzymes. Complex nutritional disturbances such as those observed in starvation, protein-deficiency malnutrition, and alcoholism are also associated with anemia.

Acronyms and abbreviations that appear in this chapter include: MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume.

The anemias that result from deficiencies of vitamin B12, folic acid (Chap. 38), or iron (Chap. 39) are clearly defined; they are relatively common and they exist in pure states. In contrast, the characteristics of anemias that may occur when there are deficiencies of micronutrients, such as some of the other vitamins, are poorly defined. Many of these deficiencies are relatively rare in humans, and when they exist it is not as isolated deficiencies of one vitamin or one mineral but, rather, as a combination of deficiencies. In this context it is impossible to deduce which abnormalities are due to which deficiency. Studies in experimental animals, on the other hand, may not accurately reflect the role of a micronutrient in humans. Accordingly, our knowledge of the effect of many micronutrients on hematopoiesis is fragmentary and based on clinical observations and interpretations that may well be flawed.
VITAMIN-DEFICIENCY ANEMIAS
VITAMIN A DEFICIENCY
Chronic deprivation of vitamin A results in anemia similar to that observed in iron deficiency.1,2,3 and 4 Mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) are reduced. Anisocytosis and poikilocytosis may be present, and serum iron levels are low. Unlike iron-deficiency anemia but similar to the anemia of chronic disease, the iron stores in the liver and marrow are increased, the serum transferrin concentration is usually normal or decreased, and the administration of medicinal iron does not correct the anemia. However, it has been suggested that vitamin A may facilitate iron absorption.5,6
Nutritional surveys conducted in developing countries have demonstrated a strong relationship between serum levels of vitamin A and blood hemoglobin concentration.7 Subjects with serum vitamin A concentrations in the range of 20 to 30 µg/dl had a mean hemoglobin concentration of 6 g/dl, compared with a mean hemoglobin level of 16 g/dl in subjects in whom the serum vitamin A concentration exceeded 60 µg/dl. Although vitamin A deficiency is recognized to occur in the United States, the relationship between it and anemia is not known.
DEFICIENCIES OF MEMBERS OF THE VITAMIN B GROUP
Isolated nutritional deficiencies of members of the vitamin B group, with the exception of folic acid and vitamin B12, are apparently very uncommon in humans, and evidence linking isolated nutritional deficiencies of pyridoxine, riboflavin, pantothenic acid, and niacin to anemia in such patients is inconclusive. Deficiency states experimentally induced in animals are more commonly associated with hematologic abnormalities.
VITAMIN B6 DEFICIENCY
Vitamin B6 includes pyridoxal, pyridoxine, and pyridoxamine. These are converted to pyridoxal 5-phosphate, which acts as a coenzyme in the decarboxylation and transamination of amino acids and in the synthesis of d-aminolevulinic acid, the porphyrin precursor. Vitamin B6 deficiency induced in infants is associated with a hypochromic microcytic anemia.8 A malnourished patient with a hypochromic anemia who failed to respond to iron therapy but subsequently responded to the administration of vitamin B6 has also been described.9 Occasionally, patients receiving therapy with antituberculosis agents, such as isoniazid, which interfere with vitamin B6 metabolism, develop a microcytic anemia that can be corrected with large doses of pyridoxine.10,11 Some patients with sideroblastic anemias (see Chap. 64) respond to the administration of pyridoxine, but these patients are not deficient in this vitamin.
RIBOFLAVIN DEFICIENCY
Riboflavin deficiency results in a decrease in red cell glutathione reductase activity, since this enzyme requires flavin adenine dinucleotide for activation. The glutathione reductase deficiency induced by riboflavin deficiency is not associated with a hemolytic anemia or increased susceptibility to oxidant-induced injury.12 Human volunteers maintained on a semisynthetic riboflavin-deficient diet and fed the riboflavin antagonist galactoflavin develop pure red cell aplasia.13 Vacuolated erythroid precursors are evident prior to the development of aplasia. This anemia is reversed specifically by the administration of riboflavin.
PANTOTHENIC ACID DEFICIENCY
Pantothenic acid deficiency, when artificially induced in humans, is not associated with anemia.14
NIACIN DEFICIENCY
Pellagra (niacin deficiency) is associated with anemia, which responds to treatment with niacin.15 However, it is not clear whether the anemia is a direct or an indirect effect of niacin deficiency.
VITAMIN C (ASCORBIC ACID) DEFICIENCY
Although approximately 80 percent of patients with scurvy16 are anemic, attempts to induce anemia in human volunteers by severe restriction of dietary ascorbic acid have been unsuccessful.17 It seems that the anemia observed in subjects with scurvy is not due directly to a deficiency of ascorbic acid but, rather, due to bleeding or a deficiency of folic acid.16 Human subjects with scurvy and megaloblastoid anemia fail to respond hematologically to vitamin C as long as they are kept on a folic acid–deficient diet. When folic acid is given to these subjects in a dose of 50 µg/day, a prompt hematologic response is observed.18
Ascorbic acid is required for the maintenance of folic acid reductase in its reduced, or active, form. Impaired folic acid reductase activity results in an inability to form tetrahydrofolic acid, the metabolically active form of folic acid. Patients with scurvy and megaloblastoid anemia excrete 10-formylfolic acid as the major urinary folate metabolite. Following ascorbic acid therapy, 5-methyltetrahydrofolic acid becomes the major urinary folate metabolite. This observation has led to the suggestion19 that ascorbic acid serves to prevent the irreversible oxidation of methyltetrahydrofolic acid to formylfolic acid. Failure to synthesize tetrahydrofolic acid or protect it from oxidation ultimately results in the appearance of a megaloblastic anemia. Under these circumstances, ascorbic acid therapy will produce a hematologic response only if enough folic acid is present to interact with the ascorbic acid.20 Dietary iron deficiency in children often occurs in association with dietary ascorbic acid deficiency. Scurvy itself may cause iron deficiency as a consequence of external bleeding. Iron balance may be further compromised by the ascorbic acid deficiency because this vitamin serves to facilitate intestinal iron absorption. Patients with scurvy, particularly children, may require both iron and vitamin C to correct a hypochromic microcytic anemia.21
In patients with iron overload from repeated blood transfusions, the level of vitamin C in leukocytes is often decreased because of rapid conversion of ascorbate to oxalate.22 Deferoxamine (desferrioxamine)-induced iron excretion is diminished when stores of vitamin C are reduced, but excretion returns to expected values with vitamin C supplementation.23,24 It has been suggested, however, that large doses of ascorbic acid may be harmful in patients with iron overload and should be given only after an infusion of desferal has been initiated (Chap. 43). The presence of scurvy in patients with iron overload may protect them from tissue damage.25 Both in scorbutic guinea pigs and in Bantu subjects with nutritional vitamin C deficiency and dietary hemosiderosis, iron accumulates in the monocyte-macrophage system rather than in the parenchymal cells of the liver.26,27
VITAMIN E DEFICIENCY
Vitamin E, a-tocopherol, is a fat-soluble vitamin that appears to serve as an antioxidant in humans and not as an essential cofactor in any recognized reactions. Nutritional deficiency of vitamin E in humans is extremely uncommon because of the widespread occurrence of a-tocopherol in food. The daily requirement for adults is in the range of 5 to 7 mg of d-a-tocopherol, but the requirement varies with the polyunsaturated fatty acid content of the diet and the content of peroxidizable lipids in tissues. Hematologic manifestations of vitamin E deficiency in humans are virtually limited to the neonatal period and to pathologic states associated with chronic fat malabsorption. Low-birth-weight infants are born with low serum and tissue concentrations of vitamin E. When these infants are fed a diet unusually rich in polyunsaturated fatty acids and inadequate in vitamin E, a hemolytic anemia will develop by 4 to 6 weeks of age, particularly if iron is also present in the diet.28 The anemia is often associated with morphologic alterations of the erythrocytes,29 thrombocytosis, and edema of the dorsum of the feet and the pretibial area.30 Treatment with vitamin E produces a prompt increase in hemoglobin level, a decrease in the elevated reticulocyte count, a normalization of the red cell life span, and a disappearance of the thrombocytosis and edema. Modifications of infant formulas have all but eliminated vitamin E deficiency in preterm infants.31
Vitamin E deficiency is common in patients with cystic fibrosis if they are not receiving daily supplements of the water-soluble form of the vitamin. Red cell life span is shortened in such patients to an average 51Cr half-life of 19 days. After vitamin E therapy, the red cell half-life increases to 27.5 days.32 Severe anemia may be present.33
Pharmacologic doses of vitamin E have been employed with apparent success in the absence of vitamin deficiency to compensate for genetic defects that limit the erythrocytes’ defense against oxidant injury. Chronic administration of 400 to 800 units of vitamin E per day lengthened the red cell life span in some34,35 and 36 but not all37 studies of patients with hereditary hemolytic anemias associated with glutathione synthetase deficiency or glucose-6-phosphate dehydrogenase deficiency.
The administration of 450 units of vitamin E per day for 6 to 36 weeks to patients with sickle cell anemia has been found to produce a significant reduction in the number of irreversibly sickled erythrocytes.38 Adult patients with sickle cell anemia have been reported to have significantly lower serum tocopherol values than do normal control subjects,39 and in children with sickle cell anemia, those with vitamin E deficiency were found to have significantly more irreversibly sickled cells than did children without vitamin E deficiency.40
TRACE METAL DEFICIENCY
COPPER DEFICIENCY
Copper is present in a number of metalloproteins. Among the cuproenzymes are cytochrome c oxidase, dopamine [beta]-hydroxylase, urate oxidase, tyrosine and lysyl oxidase, ascorbic acid oxidase, and superoxide dismutase (erythrocuprein). More than 90 percent of the copper in the blood is carried bound to ceruloplasmin, an a2-globulin with ferro-oxidase activity. Copper appears to be required for the absorption and utilization of iron. Copper, in the form of hephaestin,41 converts and maintains iron in the Fe3+ state for its transport by transferrin.
Copper deficiency has been described in malnourished children42 and in both infants and adults43,44 and 45 receiving parenteral alimentation. It is characterized by a microcytic anemia that is unresponsive to iron therapy, hypoferremia, neutropenia, and usually the presence of vacuolated erythroid precursors in the marrow.44,45 In infants and young children with copper deficiency, radiologic abnormalities are generally present. These abnormalities include osteoporosis, flaring of the anterior ribs with spontaneous rib fractures, cupping and flaring of long-bone metaphyses with spur formation and submetaphyseal fractures, and epiphyseal separation. These changes have frequently been misinterpreted as signs of scurvy. Copper deficiency with a resultant microcytic anemia can be produced by chronic ingestion of massive quantities of zinc. Dietary zinc in large doses leads to copper deficiency by impairing copper absorption.46,47,48,49 and 50
The diagnosis of copper deficiency can be established by the demonstration of a low serum ceruloplasmin or serum copper level, but the copper level is thought to be more reliable because ceruloplasmin behaves as an acute-phase protein.44 Adequate normal values for the first 2 to 3 months have not been well defined and are normally lower than those observed later in life. Despite these limitations, a serum copper level less than 40 µg/dl or a ceruloplasmin value less than 15 mg/dl after 1 or 2 months of age can be regarded as evidence of copper deficiency. In later infancy, childhood, and adulthood, serum copper values should normally exceed 70 µg/dl. Low serum copper values may be observed in hypoproteinemic states such as exudative enteropathies and nephrosis as well as in Wilson disease. In these circumstances a diagnosis of copper deficiency cannot be established by serum measurements alone but requires an analysis of liver copper content or clinical response after a therapeutic trial of copper supplementation.
The anemia and neutropenia are quickly corrected by the administration of copper. Treatment of copper-deficient infants consist of giving about 2.5 mg of copper (»80 µg/kg/day) oral supplementation as a copper sulfate solution.51 Intravenous bolus injection of copper chloride has also been used.45
ZINC DEFICIENCY
Zinc is required for a large number of zinc metalloenzymes, zinc-activated enzymes, and “zinc finger” transcription factors. Zinc deficiency occurs in a variety of pathologic states in humans, including hemolytic anemias such as thalassemia52 and sickle cell anemia.53 Zinc deficiency with or without an associated copper deficiency has been described in a patient on intensive desferrioxamine therapy54 and in patients with decreased renal reabsorption of trace minerals.55
Although human zinc deficiency may produce growth retardation, impaired wound healing, impaired taste perception, immunologic abnormalities, and acrodermatitis enteropathica, there is no evidence at present that isolated zinc deficiency produces anemia.
SELENIUM DEFICIENCY
A deficiency of selenium occurs in patients who live in areas in which the selenium content of the soil is very low56 and has been observed in patients receiving total parenteral nutrition.57,58 Although this results in a striking decrease in the level of red cell glutathione peroxidase, there do not appear to be any adverse hematologic consequences.
ANEMIA OF STARVATION
Studies conducted during World War II among prisoners of war and conscientious objectors demonstrated that semistarvation for 24 weeks can result in a mild to moderate normocytic normochromic anemia.59 Marrow cellularity is usually reduced and is accompanied by a decrease in the erythroid/myeloid ratio. Measurements of red cell volume and plasma volume suggest that dilution is a major factor responsible for the reduction in hemoglobin concentration.
In persons subjected to complete starvation either for experimental purposes or to treat severe obesity, anemia was not observed during the first 2 to 9 weeks of fasting.60 Starvation for 9 to 17 weeks produced a fall in hemoglobin and marrow hypocellularity.61 Resumption of a normal diet was accompanied by a reticulocytosis and disappearance of anemia. It has been suggested that the anemia of starvation is a response to a hypometabolic state, with its attendant decrease in oxygen requirements.62
ANEMIA OF PROTEIN DEFICIENCY (KWASHIORKOR)
Even strict vegetarians do not seem to develop hematologic problems related to the absence of animal proteins,63 except for some vegans who have been reported to suffer from B12 deficiency.64
In infants and children with protein-calorie malnutrition, the hemoglobin concentration may fall to 8 g/dl of blood,65,66 but some children with kwashiorkor have normal hemoglobin levels, probably because of a decreased plasma volume. The anemia is normocytic and normochromic, but there is considerable variation in the size and shape of red cells on the blood film. The white blood cells and the platelets are usually normal. The marrow is most often normally cellular or slightly hypocellular, with a reduced erythroid/myeloid ratio. Erythroblastopenia, reticulocytopenia, and a marrow containing a few giant pronormoblasts may be found, particularly if these children have an infection. With treatment of the infection, erythroid precursors may appear in the marrow and the reticulocyte count may rise. When nutrition is improved by giving high-protein diets (powdered milk or essential amino acids), there is reticulocytosis, a slight fall in hematocrit due to hemodilution, and then a rise in hemoglobin level, hematocrit, and red blood cell count. Improvement is very slow, however, and during the third or fourth week, when these children are clinically improved and the serum proteins are approaching normal, another episode of erythroid marrow aplasia may develop. This relapse is not associated with infection, does not respond to antibiotics, and does not remit spontaneously. It does respond either to riboflavin or to prednisone, and unless they are treated with these agents, children who develop this complication may die suddenly. It has been suggested67 that the erythroblastic aplasia is a manifestation of riboflavin deficiency.
Although the plasma volume is reduced to a variable degree in children with kwashiorkor, the total circulating red cell volume decreases in proportion to the decrease in lean body mass as protein deprivation reduces metabolic demands. During repletion, an increase in plasma volume may occur before an increase in red cell volume, and the anemia may seem to become more severe despite reticulocytosis.
From the study of the anemia of protein deficiency in rats,68 it was deduced that oxygen consumption and therefore erythropoietin production are reduced. Other studies confirmed this observation but related the reduction to calorie deprivation, with its associated decrease in the blood levels of T3 and T4.62 As a result, erythropoiesis decreases and the reticulocyte count falls. The plasma iron turnover and red cell uptake of radioactive iron are markedly reduced, and the red cell volume gradually declines.68 Protein deficiency also produces a maturation block at the erythroblast level and a slight decrease in the erythropoietin-sensitive progenitor cell pool.69 If exogenous erythropoietin is provided, normal erythropoiesis is restored despite protein depletion,70 an observation that explains the successful use of starved rats in the bioassay for erythropoietin.
ALCOHOLISM
Chronic alcohol ingestion is often associated with anemia. The anemia may be due to nutritional deficiencies, chronic gastrointestinal bleeding, hepatic dysfunction, or direct toxic effects of alcohol on erythropoiesis. Quite commonly all these factors work in concert to produce the anemia. Pyridoxal phosphate and folate deficiencies are common71 in alcoholics. Alcohol affects not only the red cells, as described here, but also the platelets (see Chap. 119).72,73
Macrocytosis is common in chronic alcoholics74 and is often associated with a megaloblastic anemia. Among hospitalized malnourished alcoholics, it is the most common type of anemia, occurring alone or in combination with ringed sideroblasts in approximately 40 percent of all patients.75,76 In contrast, megaloblastic anemia is rarely observed in nonhospitalized chronic alcoholics or relatively well-nourished subjects admitted to the hospital for purposes of alcohol withdrawal.77 Anemia, when associated with megaloblastic marrow changes in alcoholics, is almost always due to folate deficiency. Iron deficiency is often associated with folate deficiency in alcoholics.77 In patients with both nutritional deficiencies, the blood film will be “dimorphic,” with macrocytes, hypersegmented neutrophils, and hypochromic microcytes. Although liver disease is frequently present in alcoholics with megaloblastic anemia, it is not responsible for the folate deficiency. Megaloblastic anemia occurs almost exclusively in alcoholics who have been eating poorly. It is seen more commonly in heavy drinkers of wine and whiskey, substances that contain little or no folate, than in drinkers of beer, a rich source of the vitamin. Although decreased dietary folate intake appears to be a necessary factor in the etiology of the megaloblastic anemia, ethanol itself interferes with folate metabolism (see Chap. 38).78,79
However, macrocytosis does not always indicate the presence of a megaloblastic anemia,74 reticulocytosis secondary to hemolysis or bleeding, or liver disease. A so-called macrocytosis of alcoholism80 is found in as many as 82 to 96 percent of alcoholics. In these patients the macrocytosis is usually mild, with a MCV in the range of 100 to 110 fl, and anemia is usually absent. In the blood film, the macrocytes are typically round rather than oval, and neutrophil hypersegmentation is not present. The macrocytosis persists until the patient abstains from alcohol. Even then, the MCV does not become completely normal for periods of 2 to 4 months.79
Alcohol ingestion for 5 to 7 days will produce vacuolization of early red cell precursors, and the formation of vacuoles can be observed in in vitro marrow cell cultures.76,81 These changes disappear promptly when alcohol ingestion is discontinued. Vacuolization of a similar appearance occurs in subjects who are fed a phenylalanine-deficient diet, patients treated with chloramphenicol or pyrazinamide, patients in hyperosmolar coma, and individuals deficient in copper or riboflavin.80
A relatively rare hematologic complication of alcoholism is Zieve syndrome,82 consisting of transient hemolytic anemia, jaundice, hyperlipidemia, and alcohol-induced liver disease.
This chapter is based upon that contributed to the fifth edition by the late Frank A. Oski, M.D.
CHAPTER REFERENCES

1.
Blackfan KD, Wolbach SB: Vitamin A deficiency in infants: A clinical and pathological study. J Pediatr 3:679, 1933.

2.
Vitamin A and iron. Nutr Rev 47: 1989.

3.
Majia LA, Hodges RE, Arroyave G, Viteri F, Torun B: Vitamin A deficiency and anemia in Central American children. Am J Clin Nutr 30:1175, 1977.

4.
Hodges RE, Sauberlich HE, Canham JE, et al: Hematopoietic studies in vitamin A deficiency. Am J Clin Nutr 31:876, 1978.

5.
Garcia-Casal MN, Layrisse M, Solano L, et al: Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans. J Nutr 128:646, 1998.

6.
Kolsteren P, Rahman SR, Hilderbrand K, Diniz A: Treatment for iron deficiency anaemia with a combined supplementation of iron, vitamin A and zinc in women of Dinajpur, Bangladesh. Eur J Clin Nutr 53:102, 1999.

7.
Nutrition survey of Paraguay, May–August, 1965, in Nutrition Program, National Center for Chronic Disease Control, US Dept of Health, Education and Welfare. US Government Printing Office, Washington, 1967.

8.
Snyderman SE, Holt LE Jr, Carretero R, Jacobs KG: Pyridoxine deficiency in the human infant. Am J Clin Nutr 1:200, 1953.

9.
Foy H, Kondi A: Hypochromic anemias of the tropics associated with pyridoxine and nicotinic acid deficiencies. Blood 1054, 1999.

10.
McCurdy PR, Donohoe RF, Magovern M: Reversible sideroblastic anemia caused by pyrazinoic acid (pyrazinamide). Ann Intern Med 64:1280, 1966.

11.
Frimpter GW: Pyridoxine (B6) dependency syndromes. Ann Intern Med 68:1131, 1968.

12.
Beutler E, Srivastava SK: Relationship between glutathione reductase activity and drug-induced haemolytic anaemia. Nature 226:759, 1970.

13.
Lane M, Alfrey CP: The anemia of human riboflavin deficiency. Blood 22:811, 1963.

14.
Hodges RE, Bean WB, Ohlson MA, Bleiler RE: Human pantothenic acid deficiency produced by omegamethylpantothenic acid. J Clin Invest 38:1421, 1959.

15.
Spivak JL, Jackson DL: Pellagra: An analysis of 18 patients and a review of the literature. Johns Hopkins Med J 140:295, 1977.

16.
Reuler JB, Broudy VC, Cooney TG: Adult scurvy. JAMA 253:805, 1985.

17.
Hodges RE, Baker EM, Hood J, Sauberlich HE, March SC: Experimental scurvy in man. Am J Clin Nutr 22:535, 1969.

18.
Zalusky R, Herbert V: Megaloblastic anemia in scurvy with response to 50 micrograms of folic acid daily. N Engl J Med 265:1033, 1961.

19.
Stokes PL, Melikian V, Leeming RL, Portman-Graham H, Blair JA, Cooke WT: Folate metabolism in scurvy. Am J Clin Nutr 28:126, 1975.

20.
Cox EV, Meynell MJ, Northam BE, Cooke WT: The anaemia of scurvy. Am J Med 42:220, 1967.

21.
Clark NG, Sheard NF, Kelleher JF: Treatment of iron-deficiency anemia complicated by scurvy and folic acid deficiency. Nutr Rev 50:134, 1992.

22.
Wapnick AA, Lynch SR, Krawitz P, Seftel HC, Charlton RW, Bothwell TH: Effects of iron overload on ascorbic acid metabolism. BMJ 3:704, 1968.

23.
Wapnick AA, Lynch SR, Charlton RW, Seftel HC, Bothwell TH: The effect of ascorbic acid deficiency on desferrioxamine-induced urinary iron excretion. Br J Haematol 17:563, 1969.

24.
Chapman RW, Hussain MA, Gorman A, et al: Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta-thalassaemia major and iron overload. J Clin Pathol 35:487, 1982.

25.
Cohen A, Cohen IJ, Schwartz E: Scurvy and altered iron stores in thalassemia major. N Engl J Med 304:158, 1981.

26.
Lipschitz DA, Bothwell TH, Seftel HC, Wapnick AA, Charlton RW: The role of ascorbic acid in the metabolism of storage iron. Br J Haematol 20:155, 1971.

27.
Bothwell TH, Abrahams C, Bradlow BA, Charlton RW: Idiopathic and Bantu hemochromatosis. Arch Pathol 79:163, 1965.

28.
Williams ML, Shoot RJ, O’Neal PL, Oski FA: Role of dietary iron and fat on vitamin E deficiency anemia of infancy. N Engl J Med 292:887, 1975.

29.
Oski FA, Barness LA: Hemolytic anemia in vitamin E deficiency. Am J Clin Nutr 21:45, 1968.

30.
Ritchie JH, Fish MB, McMasters V, Grossman M: Edema and hemolytic anemia in premature infants: A vitamin E deficiency syndrome. N Engl J Med 279:1185, 1968.

31.
Zipursky A: Vitamin E deficiency anemia in newborn infants. Clin Perinatol 11:393, 1984.

32.
Farrell PM, Bieri JG, Fratantoni JF, Wood RE, di Sant’Agnese PA: The occurrence and effects of human vitamin E deficiency: A study in patients with cystic fibrosis. J Clin Invest 60:233, 1977.

33.
Wilfond BS, Farrell PM, Laxova A, Mischler E: Severe hemolytic anemia associated with vitamin E deficiency in infants with cystic fibrosis: Implications for neonatal screening. Clin Pediatr (Philadelphia) 33:2, 1994.

34.
Corash L, Spielberg S, Bartsocas C, et al: Reduced chronic hemolysis during high-dose vitamin E administration in Mediterranean-type glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 303:416, 1980.

35.
Hafez M, Amar ES, Zedan M, et al: Improved erythrocyte survival with combined vitamin E and selenium therapy in children with glucose-6-phosphate dehydrogenase deficiency and mild chronic hemolysis. J Pediatr 108:558, 1986.

36.
Eldamhougy S, Elhelw Z, Yamamah G, Hussein L, Fayyad I, Fawzy D: The vitamin E status among glucose-6-phosphate dehydrogenase deficient patients and effectiveness of oral vitamin E. Int J Vitam Nutr Res 58:184, 1988.

37.
Johnson GJ, Vatassery GT, Finkel B, Allen DW: High-dose vitamin E does not decrease the rate of chronic hemolysis in glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 308:1014, 1983.

38.
Natta CL, Machlin LJ, Brin M: A decrease in irreversibly sickled erythrocytes in sickle cell anemia patients given vitamin E. Am J Clin Nutr 33:968, 1980.

39.
Tangney CC, Phillips G, Bell RA, Fernandes P, Hopkins R, Wu SM: Selected indices of micronutrient status in adult patients with sickle cell anemia (SCA). Am J Hematol 32:161, 1989.

40.
Ndombi IO, Kinoti SN: Serum vitamin E and the sickling status in children with sickle cell anaemia. East Afr Med J 67:720, 1990.

41.
Vulpe CD, Kuo YM, Murphy TL, et al: Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nature Genet 21:195, 1999.

42.
Graham GG, Cordano A: Copper depletion and deficiency in the malnourished infant. Johns Hopkins Med J 124:139, 1969.

43.
Joffe G, Etzioni A, Levy J, Benderly A: A patient with copper deficiency anemia while on prolonged intravenous feeding. Clin Pediatr (Philadelphia) 20:226, 1981.

44.
Spiegel JE, Willenbucher RF: Rapid development of severe copper deficiency in a patient with Crohn’s disease receiving parenteral nutrition. J Parenter Enteral Nutr 23:169, 1999.

45.
Hirase N, Abe Y, Sadamura S, et al: Anemia and neutropenia in a case of copper deficiency: Role of copper in normal hematopoiesis. Acta Haematol (Basel) 87:195, 1992.

46.
Hoffman HN, Phyliky RL, Fleming CR: Zinc-induced copper deficiency. Gastroenterology 94:508, 1988.

47.
Patterson WP, Winkelmann M, Perry MC: Zinc-induced copper deficiency: Megamineral sideroblastic anemia. Ann Intern Med 103:385, 1985.

48.
Simon SR, Branda RF, Tindle BF, Burns SL: Copper deficiency and sideroblastic anemia associated with zinc ingestion. Am J Hematol 28:181, 1988.

49.
Summerfield AL, Steinberg FU, Gonzalez JG: Morphologic findings in bone marrow precursor cells in zinc-induced copper deficiency anemia. Am J Clin Pathol 97:665, 1992.

50.
Sandstead HH: Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am J Clin Nutr 61:621S, 1995.

51.
Cordano A: Clinical manifestations of nutritional copper deficiency in infants and children. Am J Clin Nutr 67:1012S, 1998.

52.
Fuchs GJ, Tienboon P, Linpisarn S, et al: Nutritional factors and thalassaemia major. Arch Dis Child 74:224, 1996.

53.
Prasad AS, Beck FWJ, Kaplan J, et al: Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD). Am J Hematol 61:194, 1999.

54.
Yuzbasiyan-Gurkan VA, Brewer GJ, Vander AJ, Guenther MJ, Prasad AS: Net renal tubular reabsorption of zinc in healthy man and impaired handling in sickle cell anemia. Am J Hematol 31:87, 1989.

55.
De Virgiliis S, Congia M, Turco MP, et al: Depletion of trace elements and acute ocular toxicity induced by desferrioxamine in patients with thalassaemia. Arch Dis Child 63:250, 1988.

56.
Thomson CD, Rea HM, Doesburg VM, Robinson MF: Selenium concentrations and glutathione peroxidase activities in whole blood of New Zealand residents. Br J Nutr 37:457, 1977.

57.
Kien CL, Ganther HE: Manifestations of chronic selenium deficiency in a child receiving total parenteral nutrition. Am J Clin Nutr 37:319, 1983.

58.
Cohen HJ, Brown MR, Hamilton D, Lyons-Patterson J, Avissar N, Liegey P: Glutathione peroxidase and selenium deficiency in patients receiving home parenteral nutrition: Time course for development of deficiency and repletion of enzyme activity in plasma and blood cells. Am J Clin Nutr 49:132, 1989.

59.
Keys A, Brozek J, Henschel A, et al: The Biology of Semistarvation. University of Minnesota Press, Minneapolis, 1950.

60.
Thomson TJ, Runcie J, Miller V: Treatment of obesity by total fasting for up to 249 days. Lancet 2:992, 1966.

61.
Drenick EJ, Swendseid ME, Blahd WH, Tuttle SG: Prolonged starvation as treatment for severe obesity. JAMA 187:100, 1964.

62.
Caro J, Silver R, Erslev AJ, Miller OP, Birgegard G: Erythropoietin production in fasted rats: Effects of thyroid hormones and glucose supplementation. J Lab Clin Med 98:860, 1981.

63.
Lowik MR, Schrijver J, Odink J, van den BH, Wedel M: Long-term effects of a vegetarian diet on the nutritional status of elderly people (Dutch Nutrition Surveillance System). J Am Coll Nutr 9:600, 1990.

64.
Chanarin I, Malkowska V, O’Hea AM, Rinsler MG, Price AB: Megaloblastic anaemia in a vegetarian Hindu community. Lancet 2:1168, 1985.

65.
Adams EB, Scragg JN, Naidoo BT, et al: Observations on the aetiology and treatment of anaemia in kwashiorkor. BMJ 3:451, 1967.

66.
Lunn PG, Morley CJ, Neale G: A case of kwashiorkor in the UK. Clin Nutr 17:131, 1998.

67.
Foy H, Kondi A: Comparison between erythroid aplasia in marasmus and kwashiorkor and the experimentally induced erythroid aplasia in baboons by riboflavin deficiency. Vitam Horm 26:653, 1968.

68.
Delmonte L, Aschenasy A, Eyquem A: Studies on the hemolytic nature of protein-deficiency anemia in the rat. Blood 24:49, 1964.

69.
Naets JP, Wittek M: Effect of starvation on the response to erythropoietin in the rat. Acta Haematol (Basel) 52:141, 1974.

70.
Ito K, Reissmann KR: Quantitative and qualitative aspects of steady state erythropoiesis induced in protein-starved rats by long-term erythropoietin injection. Blood 27:343, 1966.

71.
Gloria L, Cravo M, Camilo ME, et al: Nutritional deficiencies in chronic alcoholics: Relation to dietary intake and alcohol consumption. Am J Gastroenterol 92:485, 1997.

72.
Savage D, Lindenbaum J: Anemia in alcoholics. Medicine (Baltimore) 65:322, 1986.

73.
Girard DE, Kumar KL, McAfee JH: Hematologic effects of acute and chronic alcohol abuse. Hematol Oncol Clin North Am 1:321, 1987.

74.
Fernando OV, Grimsley EW: Prevalence of folate deficiency and macrocytosis in patients with and without alcohol-related illness. South Med J 91:721, 1998.

75.
Colman N, Herbert V: Hematologic complications of alcoholism: Overview. Semin Hematol 17:164, 1980.

76.
Sullivan LW, Herbert V: Suppression of hematopoiesis by ethanol. J Clin Invest 43:2048, 1964.

77.
Eichner ER, Hillman RS: Effect of alcohol on serum folate level. J Clin Invest 52:584, 1973.

78.
Lindenbaum J: Folate and vitamin B deficiencies in alcoholism deficiencies in alcoholism Semin Hematol 17:119, 1980.

79.
Seppa K, Laippala P, Saarni M: Macrocytosis as a consequence of alcohol abuse among patients in general practice. Alcohol Clin Exp Res 15:871, 1991.

80.
McCurdy PR, Rath CE: Vacuolated nucleated bone marrow cells in alcoholism. Semin Hematol 17:100, 1980.

81.
Yeung KY, Klug PP, Lessin LS: Alcohol-induced vacuolization in bone marrow cells: Ultrastructure and mechanism of formation. Blood Cells 13:487, 1988.

82.
Pilcher CR, Underwood RG, Smith HR: Zieve’s syndrome a potential surgical pitfall? J R Army Med Corps 142:84, 1996.
Books@Ovid
Copyright © 2001 McGraw-Hill
Ernest Beutler, Marshall A. Lichtman, Barry S. Coller, Thomas J. Kipps, and Uri Seligsohn
Williams Hematology

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