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638 Part VI: The Erythrocyte Chapter 43: Iron Deficiency and Overload 639

Special Studies to Delineate the Cause of Iron Deficiency occurs when iron is presented to the duodenal mucosa. Enteric-
The physician who establishes a diagnosis of iron deficiency resulting coated and prolonged-release preparations dissolve slowly in any
from blood loss has the obligation to determine the site and cause of of these fluids. Thus with such preparations the iron that eventually
hemorrhage. Examination for fecal occult blood is particularly helpful is released may be presented to a portion of the intestinal mucosa
in determining what additional studies should be carried out. Speci- in which absorption is least efficient. Some patients who have been
mens should be examined on at least 3 days, because bleeding may be treated unsuccessfully with enteric-coated or prolonged-release
intermittent. Occasionally, it is helpful to label the patient’s erythrocytes iron preparations respond promptly to the administration of non–
with chromium-51 ( Cr) sodium chromate and to determine quantita- enteric-coated ferrous salts.
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tively the amount of blood lost daily. When there is reason to believe that 3. The iron, once released, should be readily absorbed. Iron is absorbed
bleeding is from the gastrointestinal tract, roentgenographic and other in the ferrous form; consequently, only ferrous salts should be used.
imaging studies and endoscopic investigation are indicated. The other 4. Side effects should be infrequent. This seems not to be a particular
imaging studies often include gastroscopy, esophagoscopy, colonoscopy, problem for any of the common commercially available iron com-
and capsule endoscopy, and, rarely, angiography or scintigraphic stud- pounds. Despite the claims of pharmaceutical companies, there is no
ies. Numerous clinical studies indicate that intensive investigation of convincing evidence that any one effective preparation is superior in
patients, particularly men and postmenopausal women, reveals unex- this respect to any other.
pected bleeding lesions, many of which are curable or treatable. 10,193 H. 5. Inexpensive iron preparations can be as effective as the more costly
pylori infection should be sought, particularly in patients who are iron ones. The use of preparations containing several therapeutic agents
deficient but who do not seem to respond to therapy. 14,15 An iron stain is unnecessary and may increase side effects. Physicians should be
of sputum may reveal hemosiderin-laden macrophages when there is aware that if ferrous sulfate is prescribed generically, the choice of
intrapulmonary bleeding. preparation is left to the pharmacist who may dispense enteric-
coated tablets. It is advisable to specify “nonenteric” or to prescribe
THERAPY by brand name a product that is not enteric-coated. Although sub-
stances such as ascorbic acid, succinate, and fructose enhance iron
Once it has been established that a patient is deficient in iron, replace- absorption, the gain is offset to a large extent by the increase in fre-
ment therapy should be instituted. Iron may be administered orally, quency of side effects, cost of therapy, or both. There is no convincing
as simple iron salts; parenterally, as an iron-carbohydrate complex; or, evidence to support the use of chelated forms of iron or of iron in
very rarely, as a blood transfusion. In general, the oral route is preferred, combination with wetting agents.
but the intravenous route is increasingly used because of the improved
safety and convenience of new parenteral iron preparations. In most Dosage For therapy of iron deficiency in adults, the dosage should
patients, iron-deficiency anemia is a disorder of long duration and slow be sufficient to provide between 150 and 200 mg elemental iron daily.
progression, and restoration of normal hemoglobin is not urgent unless The iron may be taken orally in three or four doses 1 hour before meals.
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the patient suffers from acute cardiac problems, in which case blood Infants may be given 6 mg/kg daily in divided doses for therapy, or a
transfusion is appropriate. There is usually time to wait for normal daily dose of 12.5 mg daily for prophylaxis of iron deficiency
mechanisms of erythropoiesis to respond to the body’s needs and for Side Effects Mild gastrointestinal side effects occur occasionally in
gradual adjustment of the cardiovascular system to reexpansion of the the form of nausea, heartburn, constipation, or changes in the stool con-
total circulating erythrocyte volume. sistency. A metallic taste may be experienced. The majority of patients
tolerate the usual therapeutic doses of iron without the least side effect.
Oral Iron Therapy However, there is no doubt that some patients, perhaps 10 to 20 percent,
Dietary Therapy The patient should be encouraged to eat a diversi- experience symptoms that may be ascribed to the iron preparation and
fied diet supplying all nutritional requirements. Nonetheless, it must may be dose-dependent. In such cases, reduction of the frequency of
be emphasized that neither meat nor any other dietary article contains administration to 1 tablet a day for a few days may alleviate the symp-
enough iron to be useful therapeutically. Meat contains small amounts toms; later, the patient may be able to tolerate treatment in full dosage.
of myoglobin and hemoglobin and insignificant amounts of iron in It might also be useful to change to another iron preparation, especially
other proteins. Although heme iron is better absorbed than inorganic one with a different external appearance.
iron, the quantity of heme iron in meat is actually quite small. In fact, an Carbonyl iron has been proposed as an alternative to iron salts,
average (3-ounce) serving of steak provides only about 3 mg of iron, that on the assertion that it can be given in large doses with minimal side
is, the equivalent of only 3 mL of packed erythrocytes. Provision of suf- effects. This substance is actually metallic iron powder, with a parti-
ficient dietary iron to permit a maximal rate or recovery from iron-defi- cle size less than 5 μm. Because it is insoluble, it is not absorbed until
ciency anemia might require a daily intake of at least 10 pounds of steak. converted to the ionic form. The bioavailability of carbonyl iron has
For these and other reasons, medicinal iron is much superior to dietary been estimated to be approximately 70 percent of that of an equivalent
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iron in the therapy of iron deficiency. amount of ferrous sulfate. Oral doses as high as 600 mg three times
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Iron Preparations The pharmaceutical market is glutted with iron daily did not produce toxic effects.
preparations in nearly every conceivable form; each promoted to appeal Widespread iron supplementation in regions where malaria
to physician or patient for one reason or another. The following simple and gastrointestinal infections are highly endemic is associated with
principles may help the physician to find a way through this chaos. increased malaria transmission and childhood mortality, presumably
from increased infections. Although there is not yet a consensus on
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1. Each dose of an inorganic iron preparation for an adult should con- optimal strategy in such settings, it seems reasonable to target iron sup-
tain between 30 and 100 mg of elemental iron. Doses of this magni- plementation to children who are iron-deficient.
tude cause unpleasant side effects relatively infrequently. Smaller Acute Iron Poisoning Acute iron poisoning is usually a conse-
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doses have been popular in the past, but these may result in a slower quence of the accidental ingestion by infants or small children of iron-
recovery of the patient or no recovery at all. containing medications intended for use by adults. Any potent oral
2. The iron should be readily released in acidic or neutral gastric juice preparation may cause acute iron poisoning, and this serious disor-
or duodenal juice (usually pH 5 to 6), because maximal absorption der remains a problem, despite public awareness campaigns and safer

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