Page 568 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 36 Disorders of Iron Homeostasis 483

TABLE Differential Diagnosis of Microcytic Hypochromic Oral Iron Therapy
36.2 Anemia
Decreased Body Iron Stores Oral iron therapy should begin with a ferrous iron salt taken separately
Iron-deficiency anemia from meals in three or four divided doses and supplying a daily total of
100–200 mg of elemental iron in adults or 3 mg of iron per kilogram
Normal or Increased Body Iron Stores of body weight in children. Simple ferrous preparations are the best
6
Anemia of chronic disease absorbed and least expensive. Ferrous sulfate is the most widely used,
Defective absorption, transport, or use of iron either as tablets containing 60–70 mg of iron for adults or as a liquid
Iron-refractory iron-deficiency anemia after parenteral iron preparation for children. Administration between meals maximizes
Atransferrinemia absorption. In patients with a hemoglobin concentration less than
Aceruloplasminemia 10 g/dL, this regimen initially provides approximately 40–60 mg of iron
daily for erythropoiesis, permitting RBC production to increase to two
Divalent metal transporter 1 (DMT1 or SLC11A2) deficiency to four times the normal level and the hemoglobin concentration to
Ferroportin-associated hemochromatosis with impaired iron export (type rise by approximately 0.2 g/dL per day. An increase in the hemoglobin
4A) concentration of at least 2 g/dL after 3 weeks of therapy generally is
Heme oxygenase 1 deficiency used as the criterion for an adequate therapeutic response. For milder
Disorders of globin synthesis anemia, a single daily dose of approximately 60 mg of iron per day
Thalassemia may be adequate. After the anemia has been fully corrected, oral iron
6
Other microcytic hemoglobinopathies should be continued to replace storage iron, either empirically for
Disorders of heme synthesis: sideroblastic anemias an additional 4–6 months or until the plasma ferritin concentration
Hereditary exceeds approximately 50 µg/L.
Acquired
10
supply. Measurement of red cell zinc protoporphyrin concentration
also provides a sensitive index of functional iron deficiency, but it
is less sensitive than reticulocyte measures to acute changes in iron
Therapeutic Trial of Iron availability. 10
Microcytic hypochromic anemias resulting from disorders of
The diagnosis of iron deficiency often is confirmed by the outcome
of a therapeutic trial of iron. A specific orderly response to, and only heme synthesis (sideroblastic anemias, congenital and acquired) and
to, treatment with iron constitutes the final definitive proof that a lack disorders of globin synthesis (thalassemias, microcytic hemoglobin-
of iron is the cause of anemia. The unequivocal diagnostic response opathies) are discussed in Chapters 38 and 40, respectively. Other
consists of (1) a reticulocytosis, which begins approximately 3–5 days rare congenital or acquired defects with microcytic hypochromic
9
after adequate iron therapy is instituted, reaches a maximum on days anemia include atransferrinemia, aceruloplasminemia, divalent
8–10, and then declines; and (2) a significant increase in hemoglobin metal transporter 1 (DMT1 or SLC11A2) deficiency, some forms of
concentration, which should begin shortly after the reticulocyte peak, is ferroportin disease, heme oxygenase 1 deficiency (mutations in
invariably present by 3 weeks after iron therapy is begun, and persists HMOX1, encoding heme oxygenase 1), several inherited sideroblastic
until the hemoglobin concentration is restored to normal. The result of anemias, and a variety of other uncommon disorders.
a therapeutic trial of iron must be evaluated for possible confounding
factors, such as poor compliance with iron therapy; malabsorption of
therapeutic iron; continuing blood loss; and the effects of coexisting
conditions, especially infectious, inflammatory, or malignant disorders. Therapy
The therapeutic trial merely aids in establishing the presence of iron
deficiency. The search for underlying causes of iron deficiency must The goal of therapy for iron-deficiency anemia is to supply sufficient
6
continue despite a positive response to iron therapy. iron to repair the hemoglobin deficit and replenish storage iron.
Generally, iron therapy for iron deficiency can be deferred until the
underlying cause of the lack of iron has been identified. Oral iron is
the treatment of choice for most patients because of its effectiveness,
9
is normal or increased (Table 36.2). In patients with the genetic safety, and economy and should always be given preference over
disorder of IRIDA, iron stores may be normal or increased after parenteral iron for initial treatment (see box on Oral Iron Therapy).
8
treatment with parenteral iron. Difficulties in the evaluation of The risk of local and systemic adverse reactions restricts the use of
microcytic hypochromic disorders usually arise when direct assess- parenteral iron to patients who are unable to absorb or tolerate
11
ment of bone marrow iron is unavailable and the diagnosis depends adequate amounts of oral iron. Rarely, RBC transfusions are needed
on indirect indicators of iron status (see boxes on Iron Deficiency to prevent cardiac or cerebral ischemia in patients with severe anemia
and Coexisting Disorders and Therapeutic Trial of Iron). or to support patients whose chronic rate of iron loss exceeds the rate
Specific entities to be considered in the differential diagnosis of of replacement possible with parenteral therapy.
hypochromic microcytic disorders are listed in Table 36.2; in all Most patients are able to tolerate oral iron therapy without dif-
of these disorders, body iron stores are normal or increased. The ficulty, but 10% to 20% may have symptoms attributable to iron.
anemia of chronic disease (see Chapter 37) is the most common The most common side effects are gastrointestinal. Decreasing the
cause of anemia in hospitalized patients and generally is mild to amount of iron in each dose usually is effective in controlling side
moderate, typically developing over several weeks in patients with effects, but if symptoms persist, a reduction in frequency to a single
chronic infectious, inflammatory, or malignant disorders. In patients daily dose may be helpful. Costly iron preparations with other addi-
treated with erythropoiesis-stimulating agents for the anemia of tives, polysaccharide–iron complexes, or enteric coatings or in
chronic renal disease or other disorders, the increased iron require- sustained-release forms do not appear to offer any advantages that
ments of the erythroid marrow cannot be met by iron mobiliza- cannot be achieved by simply reducing the dose of plain ferrous salts.
tion from replete stores, resulting in iron-restricted erythropoiesis. Administering iron with food and decreasing the dose will diminish
This state, sometimes labeled functional iron deficiency despite the the amount of iron absorbed daily and thereby prolong the period of
presence of storage iron, is a form of iron-restricted erythropoiesis treatment, but haste in the correction of iron deficiency is rarely
resulting from stimulated erythropoietic demand for iron. Uncom- needed.
monly, a similar pattern can result from endogenous increases in Parenteral iron therapy (see box on Parenteral Iron Therapy), with
erythropoietin owing to anemia, hypoxemia, and other conditions. the risk of adverse reactions, should be reserved for the exceptional
The %HRC, CHr, or Ret He may be the earliest indicators that patient who (1) remains intolerant of oral iron despite repeated
stimulated erythropoietic demand for iron exceeds the available modifications in dosage regimen; (2) has iron needs that cannot be