Chapter 10: Anemia Resulting from Other Nutritional Deficiencies

Prevalent in school children in several underdeveloped African countries (e.g., Malawi).

Anemia is characterized by reduced MCV, MCHC, and anisocytosis and poikilocytosis.

Similar to the anemia of chronic disease with reduced serum iron concentration, normal or low serum total iron-binding capacity and increased liver and marrow iron stores (increased serum ferritin), and failure to respond to treatment with medicinal iron.

Responds to vitamin A repletion.

Vitamin B₆ includes pyridoxal, pyridoxine, and pyridoxamine.

May lead to hypochromic microcytic anemia.

Microcytic anemia may occur in patients taking isoniazid, which interferes with B₆ metabolism. Such anemias may be corrected with large doses of pyridoxine.

Some patients who are not vitamin B₆ deficient may have sideroblastic anemia that will partially respond to high doses of pyridoxine (see Chap. 14).

Volunteers receiving a riboflavin-deficient diet plus a riboflavin antagonist (galactoflavin) developed vacuolated erythroid precursors, followed by pure red cell aplasia—all reversed by administration of riboflavin.

Reduced erythrocyte glutathione reductase activity occurs in riboflavin deficiency but is not associated with hemolysis or oxidant-induced injury.

Anemia in humans with scurvy may be macrocytic, normocytic, or microcytic, and the marrow may be hypocellular, normocellular, or hypercellular. In 10 percent of patients, the marrow is megaloblastic.

Macrocytic anemia may develop with vitamin C deficiency because vitamin C interacts with folic acid in the generation of tetrahydrofolic acid.

Microcytic anemia may develop because vitamin C facilitates the absorption of iron and because of the bleeding manifestation of scurvy.

Iron deficiency in children is often associated with dietary vitamin C deficiency.

Normocytic normochromic anemia with a reticulocytosis of 5 to 10 percent also develops in scurvy, perhaps from compromised cellular antioxidant defense mechanisms.

The anemia of vitamin C deficiency responds promptly to administration of vitamin C. Sufficient folic acid and iron is required for the response to occur.

The vitamin E requirement varies with polyunsaturated fatty acid content of diet and the content of lipids that can peroxidize in tissues.

Perinatal period: Low-birth-weight infants have low serum and tissue concentrations of vitamin E.

A diet rich in polyunsaturated fatty acids and adequate in iron but inadequate in vitamin E may lead to hemolytic anemia by 4 to 6 weeks of age.

Anemia is often associated with altered red cell morphology, thrombocytosis, and edema of the dorsum of the feet and pretibial area.

These abnormalities are reversed promptly by treatment with vitamin E.

Chronic fat malabsorption, such as is common in cystic fibrosis, can lead to vitamin E deficiency, if daily supplements of the water-soluble form of this vitamin are not given. In such patients, the red cell life span is mildly reduced and anemia may develop.

Patients with sickle cell disease often have low serum tocopherol concentrations. Vitamin E deficiency has been associated with an increase in irreversibly sickled cells in the blood. Vitamin E (450 units/day) has been associated with a decrease in irreversibly sickled cells.

Copper is required for absorption and utilization of iron, perhaps functioning by maintaining iron in the ferric state for transferrin transport.

Copper deficiency occurs in malnourished children and in infants and adults receiving parenteral alimentation, and can also be caused by chronic ingestion of massive quantities of zinc, which impairs copper absorption.

Young children with copper deficiency may have osteoporosis, flaring of ribs, and other bony abnormalities.

Copper deficiency causes a microcytic anemia with hypoferremia, neutropenia, and vacuolated erythroid precursors in marrow that does not respond to iron therapy.

Copper deficiency can occur after gastric resection or after bariatric gastric reduction surgery. The macrocytic anemia, neutropenia, and ringed sideroblasts in the marrow can mimic closely the clonal anemia seen in the myelodysplastic syndrome.

Copper deficiency can be associated with secondary neurologic abnormalities, especially myeloneuropathy. Anemia in this situation can mimic cobalamin deficiency and should be considered in the differential diagnosis of the latter, especially in individuals post-gastrectomy.

Diagnosis is established by demonstration of low serum ceruloplasmin or copper levels, or by a therapeutic trial with copper at a dose of 0.2 mg/kg day. Copper levels are the more reliable because ceruloplasmin is an acute phase reactant. A 10 percent solution of copper sulfate contains 25 mg of copper per milliliter.

Low serum copper values may also be seen in hypoproteinemic states (exudative enteropathies, nephrosis) and Wilson disease (see Chap. 22).

May accompany thalassemia or sickle cell disease.

Isolated zinc deficiency does not produce anemia.

Zinc deficiency can result in growth retardation in children, impaired wound healing, impaired taste perception, and immunologic inadequacies.

Table 10–1 contains the normal levels in blood for the vitamins and minerals discussed above.

Semistarvation causes mild to moderate normocytic normochromic anemia with reduced marrow erythroid precursors. The anemia is principally dilutional.

Complete starvation for 9 to 12 weeks leads to anemia and marrow hypocellularity, which responds to resumption of a normal diet. The decreased hemoglobin may be a response to a hypometabolic state with consequent decrease in oxygen requirements. Reticulocytosis and correction of the hemoglobin deficit follows refeeding.

In protein-calorie malnutrition, the hemoglobin level may fall to 8 g/dL, but some children may not be anemic because the reduced red cell mass is masked by a reduced plasma volume.

Anemia is normocytic, normochromic, with significant anisocytosis and poikilocytosis.

Leukocyte and platelet counts are usually normal.

The marrow is usually normocellular or hypocellular with reduced erythroid precursors.

Patients respond slowly to high-protein diets (powdered milk or essential amino acids).

After 3 or 4 weeks of treatment, there may be an episode of erythroid aplasia that responds to riboflavin or prednisone.

Occult deficiencies may become manifest during the repletion period; e.g., iron, folic acid, vitamin E, and vitamin B₁₂.

Chronic alcohol ingestion is often associated with anemia, which may be a result of multiple causes:

— Nutritional deficiencies.

— Chronic gastrointestinal bleeding.

— Hepatic dysfunction.

— Hemolytic anemia.

— Hypersplenism from portal hypertension.

— Direct toxic effects of ethanol on erythropoiesis and on folate metabolism.

Macrocytic anemia occurs commonly in hospitalized alcoholic patients and is often associated with megaloblastic changes and sometimes with ringed sideroblasts.

Megaloblastic anemia in alcoholism is almost always caused by folic acid deficiency.

Megaloblastic anemia is more common in drinkers of wine or whiskey, which have low folate content, than in drinkers of beer, which is a rich source of folate.

Alcoholics may have associated iron deficiency, producing a "dimorphic" blood picture (macrocytes, hypersegmented neutrophils, and hypochromic microcytes).

Iron deficiency may be unmasked after treatment with folic acid alone by demonstration of an emerging population of microcytic red cells. Treatment with iron alone may unmask folate deficiency, by demonstration of an emerging population of macrocytes.

Mild macrocytosis (MCV 100 to 110 fL) is found in 82 to 96 percent of chronic alcoholics. Anemia is usually absent, macrocytes are typically round as opposed to oval and neutrophil hypersegmentation is not present. These patients are not folate deficient, and the macrocytosis persists until the patient abstains from alcohol.