640 SECTION 6 Problems of Oxygenation: Transport
occurs with chronic transfusion therapy.11 Folic acid is given if
there is evidence of hemolysis. Transfusions are administered
to keep the hemoglobin level at approximately 10 g/dL (100 g/L)
to maintain the patient’s own erythropoiesis without causing the
spleen to enlarge. Zinc supplementation may be needed, since
zinc is reduced with chelation therapy. Ascorbic acid supple-
mentation may be needed during chelation therapy, since it
increases urine excretion of iron. Other than during chelation
therapy, ascorbic acid should not be taken because it increases
the absorption of dietary iron. Iron supplements should not be
given.
Because RBCs are sequestered in the enlarged spleen, thalas-
semia major may be treated by splenectomy. Hepatic, cardiac,
and pulmonary organ function should be monitored and treated
as appropriate.
Although hematopoietic stem cell transplantation (HSCT)
remains the only cure for patients with thalassemia, the risk of
this procedure may outweigh its benefits. With proper iron
chelation therapy, patients are living longer.
MEGALOBLASTIC ANEMIAS
Megaloblastic anemias are a group of disorders caused by
impaired DNA synthesis and characterized by the presence of
large RBCs. When DNA synthesis is impaired, defective RBC
maturation results. The RBCs are large (macrocytic) and abnor-
mal and are referred to as megaloblasts. Macrocytic RBCs are
easily destroyed because they have fragile cell membranes.
Although the overwhelming majority of megaloblastic anemias
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-
der characterized by a proliferation of erythropoietic cells in
bone marrow) (Table 31-8).
Cobalamin (Vitamin B12) Deficiency
Normally, a protein termed intrinsic factor (IF) is secreted by
the parietal cells of the gastric mucosa. IF is required for cobal-
amin (extrinsic factor) absorption. (Cobalamin is normally
absorbed in the distal ileum.) Therefore if IF is not secreted,
cobalamin will not be absorbed.
Etiology
Pernicious Anemia. The most common cause of cobalamin
deficiency is pernicious anemia, which is caused by an absence
of IF. In pernicious anemia the gastric mucosa is not secreting
IF because of either gastric mucosal atrophy or autoimmune
destruction of parietal cells. In the autoimmune process anti-
bodies are directed against the gastric parietal cells and/or
IF itself. Because parietal cells also secrete hydrochloric acid
(HCl), in pernicious anemia there is a decrease in HCl in the
stomach. An acid environment in the stomach is required for
the secretion of IF.
Pernicious anemia is a disease of insidious onset that begins
in middle age or later (usually after age 40), with 60 years being
the most common age at diagnosis. Pernicious anemia occurs
frequently in persons of Northern European ancestry (particu-
larly Scandinavians) and African Americans. In African Amer-
icans the disease tends to begin early, occurs with higher
frequency in women, and is often severe.
TABLE 31-8 CLASSIFICATION OF
MEGALOBLASTIC ANEMIA
Coba la min (Vita min B12) Deficiency
• Dietary deficiency
• Deficiency of gastric intrinsic factor
• Pernicious anemia
• Gastrectomy
• Intestinal malabsorption
• Increased requirement
• Chronic alcoholism
Folic Acid Deficiency
• Dietary deficiency (e.g., leafy green vegetables, citrus fruits)
• Malabsorption syndromes
• Drugs interfering with absorption or use of folic acid
• Methotrexate
• Antiseizure drugs (e.g., phenobarbital, phenytoin [Dilantin])
• Increased requirement
• Alcohol abuse
• Anorexia
• Hemodialysis patients (folic acid lost during dialysis)
Drug-Induced Suppression of DNA Synthesis
• Folate antagonists
• Metabolic inhibitors
• Alkylating agents
Inborn Errors
• Defective folate metabolism
• Defective transport of cobalamin
Erythroleukemia
Other Causes of Cobalamin Deficiency. Cobalamin defi-
ciency can also occur in patients who have had GI surgery (e.g.,
gastrectomy, gastric bypass); patients who have had a small
bowel resection involving the ileum; and patients with Crohn’s
disease, ileitis, celiac disease, diverticuli of the small intestine,
or chronic atrophic gastritis (see Table 31-8). In these cases,
cobalamin deficiency results from the loss of IF-secreting gastric
mucosal cells or impaired absorption of cobalamin in the distal
ileum. Cobalamin deficiency is also found in chronic alcoholics,
long-term users of H2-histamine receptor blockers and proton
pump inhibitors, and those who are strict vegetarians.2,3
Clinical Manifestations
General manifestations of anemia related to cobalamin defi-
ciency develop because of tissue hypoxia (see Table 31-3). GI
manifestations include a sore, red, beefy, and shiny tongue;
anorexia, nausea, and vomiting; and abdominal pain. Typical
neuromuscular manifestations include weakness, paresthesias
of the feet and hands, reduced vibratory and position senses,
ataxia, muscle weakness, and impaired thought processes
ranging from confusion to dementia. Because cobalamin
deficiency–related anemia has an insidious onset, it may take
several months for these manifestations to develop.
Diagnostic Studies
Laboratory data reflective of cobalamin deficiency anemia are
presented in Table 31-6. The RBCs appear large (macrocytic)
and have abnormal shapes. This structure contributes to eryth-
rocyte destruction because the cell membrane is fragile. Serum
cobalamin levels are reduced.