Page 678 - Williams Hematology ( PDFDrive )

652 Part VI: The Erythrocyte Chapter 44: Anemia Resulting From Other Nutritional Deficiencies 653

VITAMIN E DEFICIENCY by anemia, often macrocytic, that is unresponsive to iron therapy;
Vitamin E, α-tocopherol, is a fat-soluble vitamin that appears to be an hypoferremia; neutropenia; and, usually, the presence of vacuolated
57–60
antioxidant in humans. It is not an essential cofactor in any recognized erythroid and granulocytic precursors in marrow. The mechanism
reactions. Nutritional deficiency of vitamin E in humans is extremely of neutropenia remains unknown, but there is some evidence that cop-
uncommon because of the widespread occurrence of α-tocopherol in per deficiency results in inhibition of differentiation and self-renewal
61,62
food. The daily requirement of d-α-tocopherol for adults ranges from of CD34(+) hematopoietic progenitor cells. Iron-containing plasma
5 to 7 mg, but this requirement varies with the polyunsaturated fatty cells, a decrease in granulocyte precursors and ring sideroblasts have
59,60
acid content of the diet and the content of peroxidizable lipids in tis- also been reported. Consequently, copper deficiency should enter
sues. Hematologic manifestations of vitamin E deficiency in humans are the differential diagnosis in patients with features of myelodysplastic
limited to the neonatal period and to pathologic states associated with syndrome, particularly if there is a history of previous gastric surgery
60
chronic fat malabsorption. (Chap. 87).
Low-birthweight infants are born with low serum and tissue con- Copper deficiency should be considered in the differential diagno-
centrations of vitamin E. When these infants are fed a diet unusually sis of a patient with anemia and associated myeloneuropathy suspected
rich in polyunsaturated fatty acids and inadequate in vitamin E, hemo- of having cobalamin deficiency with subacute combined degeneration
lytic anemia frequently develops by 4 to 6 weeks of age, particularly if of the spinal cord; neurologic findings, most commonly the result of
63,64
iron is also present in the diet. This anemia often is associated with myeloneuropathy, are frequently present.
41
morphologic alterations of the erythrocytes, thrombocytosis, and Radiologic abnormalities generally are present in infants and
42
edema of the dorsum of the feet and pretibial area. Treatment with young children with copper deficiency. These abnormalities include
43
vitamin E produces a prompt increase in hemoglobin level, a decrease osteoporosis, flaring of the anterior ribs with spontaneous rib fractures,
in the elevated reticulocyte count, normalization of red cell life span, cupping and flaring of long-bone metaphyses with spur formation and
and disappearance of thrombocytosis and edema. Modifications of submetaphyseal fractures, and epiphyseal separation. These changes are
infant formulas have all but eliminated vitamin E deficiency in preterm frequently misinterpreted as signs of scurvy.
infants. 44 Copper deficiency with resultant microcytic anemia can be pro-
Vitamin E deficiency is common in patients with cystic fibrosis duced by chronic ingestion of massive quantities of zinc. This has been
who are not receiving daily supplements of a water-soluble form of the reported in patients using excessive quantities of zinc-containing dental
65,66
vitamin. Red cell life span in such patients is shortened to an aver- fixatives. Dietary zinc in large doses leads to copper deficiency by
45
67,68
age chromium-51 ( Cr) half-life of 19 days (normal: approximately 30 impairing copper absorption.
51
days). Severe anemia may be present. After vitamin E therapy, red cell The diagnosis of copper deficiency can be established by demon-
45
half-life increases to 27.5 days. 46 strating a low serum ceruloplasmin or serum copper level, but the cop-
Pharmacologic doses of vitamin E have been employed with per level is thought to be more reliable because ceruloplasmin behaves
59
apparent success in the absence of vitamin deficiency to compensate as an acute-phase protein. Adequate normal values for the first 2 to 3
for genetic defects that limit erythrocyte defense against oxidant injury. months of life are not well defined and normally are lower than the lev-
Chronic administration of oral vitamin E 400 to 800 U/day lengthened els observed later in life. Despite these limitations, a serum copper level
red cell life span in some, 47,48 but not all, studies of patients with hered- less than 70 mcg/dL (11 μmol/L) or ceruloplasmin level less than 15 mg/
49
itary hemolytic anemias associated with glutathione synthetase defi- dL after age 1 or 2 months can be regarded as evidence of copper defi-
ciency or glucose-6-phosphate dehydrogenase deficiency. ciency. In later infancy, childhood, and adulthood, serum copper values
Administration of vitamin E (450 U/day for 6 to 36 weeks) to should normally exceed 70 mcg/dL. Low serum copper values may be
patients with sickle cell anemia significantly reduced the number of observed in hypoproteinemic states, such as exudative enteropathies
irreversibly sickled erythrocytes. Adult patients with sickle cell anemia and nephrosis, and Wilson disease. In these circumstances, a diagno-
50
have been reported to have significantly lower serum tocopherol val- sis of copper deficiency cannot be established by serum measurements
ues compared with normal controls, 51,52 and in children with sickle cell alone but requires analysis of liver copper content or clinical response
anemia, those with vitamin E deficiency have significantly more irre- after a therapeutic trial of copper supplementation.
versibly sickled cells than did children without vitamin E deficiency. 53 Copper-deficiency anemia and neutropenia are quickly corrected
by administration of copper. Treatment of copper-deficient infants
consists of administration of approximately 2.5 mg of copper (approx-
imately 80 mcg/kg per day) oral supplementation as a copper sulfate
TRACE METAL DEFICIENCY solution. Intravenous bolus injection of copper chloride also has been
69
used. 60
COPPER DEFICIENCY
Copper is present in a number of metalloproteins. Cytochrome c oxi-
dase, dopamine β-hydroxylase, urate oxidase, tyrosine and lysyl oxi- ZINC DEFICIENCY
dase, ascorbic acid oxidase, and superoxide dismutase (erythrocuprein) Zinc is required for a large number of zinc metalloenzymes, zinc-
are cuproenzymes. More than 90 percent of copper in the blood is car- activated enzymes, and “zinc finger” transcription factors. Zinc defi-
ried bound to ceruloplasmin, an α -globulin with ferroxidase activity. ciency occurs in a variety of pathologic states in humans, including
2
Copper is required for absorption and utilization of iron. Copper, in hemolytic anemias such as thalassemia and sickle cell anemia. Zinc
70
71
3+
the form of hephaestin, converts iron to the ferric (Fe ) state for its deficiency with or without an associated copper deficiency has been
54
72
transport by transferrin. described in a patient receiving intensive desferrioxamine therapy and
Copper deficiency has been described in malnourished children, in patients with decreased renal reabsorption of trace minerals. 73
55
and in both infants and adults receiving parenteral alimentation. 56–58 Although human zinc deficiency may produce growth retarda-
There is increasing recognition of copper deficiency associated with tion, impaired wound healing, impaired taste perception, immunologic
anemia occurring as a complication following gastric resection or abnormalities, and acrodermatitis enteropathica, at present there is no
59
bariatric gastric reduction surgery. Copper deficiency is characterized evidence that isolated zinc deficiency produces anemia.

Kaushansky_chapter 44_p0651-0656.indd 653 9/17/15 6:30 PM