DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Normal
Iron Depletion
Iron-Deficient
Erythropoiesis
Iron-Deficiency
Anemia
1081
Iron Stores
Erythron Iron
RE marrow Fe
Transferrin
μg/100 ml (μM)
Plasma ferritin, μg/l 100 ± 60 20 10 <10
Iron absorption, % 5–10 10–15 10–20 10–20
Plasma iron
μg/100 ml (μM)
Transferrin saturation, % 35 ± 15 30 <15
Sideroblasts, % 40–60 40–60 <10
RBC protoporphyrin
μg/100 ml RBC
(μmol per liter RBC)
2–3+ 0–1 + 0 0
330 ± 30
(59 ± 5)
115 ± 50
(21 ± 9)
30
(0.53)
360
(64)
115
(21)
30
(0.53)
390
(70)
<60
(<11)
100
(1.8)
410
(73)
<40
(<7)
Erythrocytes Normal Normal Normal Microcytic/
hypochromic
<10
<10
200
(3.5)
CHAPTER 37
HEMATOPOIETIC AGENTS
Figure 37–5. Sequential changes (from left to right) in the development of iron deficiency in the adult. Red rectangles indicate abnormal
test results. RE marrow Fe, reticuloendothelial hemosiderin; RBC, red blood cells. (Adapted from Hillman RS and Finch CA. Red
Cell Manual, 7th ed. FA Davis Co., Philadelphia, 1997. Used with permission.)
The recognition of iron deficiency rests on an appreciation
of the sequence of events that lead to depletion of iron stores.
A negative balance first results in a reduction of iron stores and
eventually a parallel decrease in red-cell iron and iron-related
enzymes (Figure 37–5). In adults, depletion of iron stores may
be recognized by a plasma ferritin <12 μg/L and the absence of
reticuloendothelial hemosiderin in the marrow aspirate. Iron-deficient
erythropoiesis is identified by a decreased saturation of
transferrin to <16% and/or by an increase above normal in redcell
protoporphyrin. Iron-deficiency anemia is associated with a
recognizable decrease in the concentration of hemoglobin in
blood. However, the physiological variation in hemoglobin levels
is so great that only about half the individuals with iron-deficient
erythropoiesis are identified from their anemia. Moreover, socalled
normal hemoglobin and iron values in infancy and childhood
are lower because of the more restricted supply of iron in
young children (Dallman et al., 1980).
In mild iron deficiency, identifying the underlying cause is
more important than any symptoms related to the deficiency state.
Because of the frequency of iron deficiency in infants and in menstruating
or pregnant women, the need for exhaustive evaluation of
such individuals usually is determined by the severity of the anemia.
However, iron deficiency in men or postmenopausal women necessitates
a search for a site of bleeding.
Although the presence of microcytic anemia is the most common
indicator of iron deficiency, laboratory tests—such as measurement
of transferrin saturation, red-cell protoporphyrin, and plasma
ferritin—are required to distinguish iron deficiency from other
causes of microcytosis. Such measurements are particularly useful
when circulating red cells are not yet microcytic because of the
recent nature of blood loss, but iron supply nonetheless limits erythropoiesis.
More difficult is the differentiation of true iron deficiency
from iron-deficient erythropoiesis due to inflammation. In
the latter condition, iron stores actually are increased, but the release
of iron from reticuloendothelial cells is blocked, the concentration of
iron in plasma is decreased, and the supply of iron to the erythroid
marrow becomes inadequate. The increased stores of iron in this condition
may be demonstrated directly by examination of an aspirate
of marrow or may be inferred from determination of an elevated
plasma concentration of ferritin.
Treatment of Iron Deficiency
General Therapeutic Principles. The response of irondeficiency
anemia to iron therapy is influenced by several
factors, including the severity of anemia, the ability
of the patient to tolerate and absorb medicinal iron, and
the presence of other complicating illnesses. Therapeutic
effectiveness is best measured by the resulting increase
in the rate of production of red cells. The magnitude of
the marrow response to iron therapy is proportional to
the severity of the anemia (level of erythropoietin stimulation)
and the amount of iron delivered to marrow
precursors.
The patient’s ability to tolerate and absorb medicinal
iron is a key factor in determining the rate of
response to therapy. The small intestine regulates
absorption, and with increasing doses of oral iron,