Agents Used in
Anemias; Hematopoietic Growth Factors
Hematopoiesis,
the production from undifferentiated stem cells of circulating erythrocytes,
platelets, and leukocytes, is a remarkable process that produces over 200
billion new blood cells per day in the normal person and even greater numbers
of cells in people with conditions that cause loss or destruction of blood
cells. The hematopoietic machinery resides primarily in the bone marrow in
adults and requires a constant supply of three essential nutrients—iron, vitamin B12, and folic acid—as well as the pres-ence of hematopoietic growth factors, proteins
that regulate the proliferation and differentiation of hematopoietic cells.
Inadequate supplies of either the essential nutrients or the growth factors
result in deficiency of functional blood cells. Anemia, a deficiency in oxygen-carrying erythrocytes, is the most common and several
forms are easily treated.
Sickle cell anemia, a
condition resulting from a genetic alteration in the hemoglobin molecule, is
common but is not easily treated. It is discussed in the Box: Sickle Cell
Disease and Hydroxyurea. Thrombocytopenia
and neutropenia are not rare, and
some forms are amenable to drug therapy. In this section, we first consider
treatment of anemia due to deficiency of iron, vitamin B12, or folic acid and
then turn to the medical use of hematopoietic growth factors to combat anemia,
thrombocytopenia, and neutrope-nia, and to support stem cell transplantation.
A 65-year-old woman with a long-standing history of poorly con-trolled type 2 diabetes mellitus presents with increasing numbness and paresthesias in her extremities, generalized weakness, a sore tongue, and gastrointestinal discomfort. Physical examination reveals a frail-looking, pale woman with diminished vibration sensation, diminished spinal reflexes, and a positive Babinski sign. Examination of her oral cavity reveals Hunter’s glossitis, in which the tongue appears deep red in color and abnormally smooth and shiny due to atrophy of the lingual papillae. Laboratory testing reveals a macrocytic anemia based on a hematocrit of 30% (normal for women, 37–48%), a hemoglobin concentration of 9.4 g/dL (normal for elderly women, 11.7–13.8 g/dL), an ery-throcyte mean cell volume (MCV) of 123 fL (normal, 84–99 fL), an erythrocyte mean cell hemoglobin concentration (MCHC) of 34% (normal, 31–36%), and a low reticulocyte count. Further laboratory testing reveals a normal serum folate concentration and a serum vitamin B12 (cobalamin) concentration of 98 pg/mL (normal, 250–1100 pg/mL). Results of a Schilling test indicate a diagnosis of pernicious anemia. Once megaloblastic anemia was identified, why was it important to measure serum concentrations of both folic acid and cobalamin? Should this patient be treated with oral or parenteral vitamin B12?
This patient’s megaloblastic anemia appears to be due to vitamin B12 (cobalamin) deficiency secondary to impaired production of intrinsic factor resulting in insufficient absorp-tion of vitamin B12 from the GI tract. It is important to mea-sure serum concentrations of both folic acid and cobalamin because megaloblastic anemia can result from deficiency of either nutrient. It is especially important to diagnose vitamin B12 deficiency because this deficiency, if untreated, can lead to irreversible neurologic damage. Folate supplementation,which can compensate for vitamin B12-derived anemia, does not prevent B12-deficiency neurologic damage. To correct this patient’s vitamin B12 deficiency, she would probably be treated parenterally with cobalamin because of her impaired oral absorption of vitamin B12. Several weeks of daily admin-istration would be followed with weekly doses until her hematocrit returned to normal. Monthly doses would then be given to maintain her body stores of vitamin B12.
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