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640 SECTION 6 Problems of Oxygenation: Transport

occurs with chronic transfusion therapy.11 Folic acid is given if TABLE 31-8 CLASSIFICATION OF
there is evidence of hemolysis. Transfusions are administered MEGALOBLASTIC ANEMIA
to keep the hemoglobin level at approximately 10 g/dL (100 g/L)
to maintain the patient’s own erythropoiesis without causing the Coba la min (Vita min B12) Deficiency
spleen to enlarge. Zinc supplementation may be needed, since • Dietary deficiency
zinc is reduced with chelation therapy. Ascorbic acid supple- • Deficiency of gastric intrinsic factor
• Pernicious anemia
mentation may be needed during chelation therapy, since it
• Gastrectomy
increases urine excretion of iron. Other than during chelation • Intestinal malabsorption
therapy, ascorbic acid should not be taken because it increases • Increased requirement
the absorption of dietary iron. Iron supplements should not be • Chronic alcoholism
Because RBCs are sequestered in the enlarged spleen, thalas- Folic Acid Deficiency
semia major may be treated by splenectomy. Hepatic, cardiac, • Dietary deficiency (e.g., leafy green vegetables, citrus fruits)
• Malabsorption syndromes
and pulmonary organ function should be monitored and treated • Drugs interfering with absorption or use of folic acid
as appropriate. • Methotrexate
Although hematopoietic stem cell transplantation (HSCT) • Antiseizure drugs (e.g., phenobarbital, phenytoin [Dilantin])
remains the only cure for patients with thalassemia, the risk of • Increased requirement
this procedure may outweigh its benefits. With proper iron • Alcohol abuse
chelation therapy, patients are living longer. • Anorexia
• Hemodialysis patients (folic acid lost during dialysis)

MEGALOBLASTIC ANEMIAS Drug-Induced Suppression of DNA Synthesis

• Folate antagonists
Megaloblastic anemias are a group of disorders caused by • Metabolic inhibitors
impaired DNA synthesis and characterized by the presence of • Alkylating agents
large RBCs. When DNA synthesis is impaired, defective RBC
maturation results. The RBCs are large (macrocytic) and abnor- Inborn Errors
• Defective folate metabolism
mal and are referred to as megaloblasts. Macrocytic RBCs are • Defective transport of cobalamin
easily destroyed because they have fragile cell membranes.
Although the overwhelming majority of megaloblastic anemias Erythroleukemia
result from cobalamin (vitamin B12) and folic acid deficiencies,
this type of RBC deformity can also occur from suppression of
DNA synthesis by drugs, inborn errors of cobalamin and folic
acid metabolism, and erythroleukemia (malignant blood disor- Other Causes of Cobalamin Deficiency. Cobalamin defi-
der characterized by a proliferation of erythropoietic cells in ciency can also occur in patients who have had GI surgery (e.g.,
bone marrow) (Table 31-8). gastrectomy, gastric bypass); patients who have had a small
bowel resection involving the ileum; and patients with Crohn’s
Cobalamin (Vitamin B12) Deficiency disease, ileitis, celiac disease, diverticuli of the small intestine,
or chronic atrophic gastritis (see Table 31-8). In these cases,
Normally, a protein termed intrinsic factor (IF) is secreted by cobalamin deficiency results from the loss of IF-secreting gastric
the parietal cells of the gastric mucosa. IF is required for cobal- mucosal cells or impaired absorption of cobalamin in the distal
amin (extrinsic factor) absorption. (Cobalamin is normally ileum. Cobalamin deficiency is also found in chronic alcoholics,
absorbed in the distal ileum.) Therefore if IF is not secreted, long-term users of H2-histamine receptor blockers and proton
cobalamin will not be absorbed. pump inhibitors, and those who are strict vegetarians.2,3

Etiology Clinical Manifestations

Pernicious Anemia. The most common cause of cobalamin General manifestations of anemia related to cobalamin defi-
deficiency is pernicious anemia, which is caused by an absence ciency develop because of tissue hypoxia (see Table 31-3). GI
of IF. In pernicious anemia the gastric mucosa is not secreting manifestations include a sore, red, beefy, and shiny tongue;
IF because of either gastric mucosal atrophy or autoimmune anorexia, nausea, and vomiting; and abdominal pain. Typical
destruction of parietal cells. In the autoimmune process anti- neuromuscular manifestations include weakness, paresthesias
bodies are directed against the gastric parietal cells and/or of the feet and hands, reduced vibratory and position senses,
IF itself. Because parietal cells also secrete hydrochloric acid ataxia, muscle weakness, and impaired thought processes
(HCl), in pernicious anemia there is a decrease in HCl in the ranging from confusion to dementia. Because cobalamin
stomach. An acid environment in the stomach is required for deficiency–related anemia has an insidious onset, it may take
the secretion of IF. several months for these manifestations to develop.
Pernicious anemia is a disease of insidious onset that begins
in middle age or later (usually after age 40), with 60 years being Diagnostic Studies
the most common age at diagnosis. Pernicious anemia occurs Laboratory data reflective of cobalamin deficiency anemia are
frequently in persons of Northern European ancestry (particu- presented in Table 31-6. The RBCs appear large (macrocytic)
larly Scandinavians) and African Americans. In African Amer- and have abnormal shapes. This structure contributes to eryth-
icans the disease tends to begin early, occurs with higher rocyte destruction because the cell membrane is fragile. Serum
frequency in women, and is often severe. cobalamin levels are reduced.