Iron deficiency may be produced in three ways: (1) iron intake not sufficient to replace normal iron losses, (2) iron not available for erythropoiesis despite adequate body iron, and (3) increased loss of body iron (blood loss) not adequately replaced by normal intake.

Acute blood loss can usually be handled without difficulty if the bleeding episode is not too prolonged and if tissue iron stores are adequate. The anemia that develops from acute bleeding is normocytic and normochromic and is not the type characteristic of chronic iron deficiency (acute changes in hematocrit level are discussed elsewhere. Chronic bleeding, however, is often sufficient to exhaust body iron stores from continued attempts by the bone marrow to restore the blood Hb level. If this occurs, a hypochromic-microcytic anemia eventually develops. Chronic bleeding may be in the form of slow, tiny, daily losses; intermittent losses of small to moderate size not evident clinically; or repeated, more widely spaced, larger bleeding episodes. Chronic iron deficiency may develop with normal diet but is hastened if the diet is itself borderline or deficient in iron.

Chronic iron deficiency is common among infants, usually from deficient dietary intake. The infant grows rapidly and must make Hb to keep up with expanding blood volume. Most of the infant’s iron comes from fetal Hb present at birth. Since premature infants have a smaller birth weight on the average, they also tend to have a smaller Hb mass than term infants. The premature infant is thus more likely than the term infant to develop clinical iron deficiency at age 6 months to 2 years, when the demands of rapid growth are most likely to produce iron depletion. Breast milk contains a marginally adequate iron content, but cow’s milk is definitely low in available iron. Whether iron deficiency occurs will therefore depend on infant birth weight, the type of milk received, and the length of milk feeding before supplementation or replacement by other foods. It has been estimated that 15%-20% of infants between 9 and 12 months of age have some degree of iron deficiency and possibly up to 50% in low socioeconomic groups.

In adults, iron deficiency from inadequate diet alone more frequently is subclinical rather than severe enough to produce anemia. However, poor iron intake may potentiate the effects of iron deficiency from other etiologies, such as menstruation. In one study, about 5% of clinically healthy white female adolescents were found to have chronic iron deficiency anemia, with about 9% of others having nonanemic iron deficiency. Iron deficiency is frequent in malabsorption diseases such as sprue, which, strictly speaking, represents inability to use available dietary iron rather than a true dietary deficiency. Another cause is pregnancy, in which iron deficiency is caused by maternal iron utilization by the fetus superimposed on previous iron deficiency due to excessive menstrual bleeding or multiple pregnancies. About 50% of chronic alcoholics and 20%-40% of patients with megaloblastic anemia are said to have some degree of iron deficiency. An interesting related condition is long-distance runner or jogger anemia, said to occur in about 40% of women active in these sports and to be caused by a combination of iron deficiency from poor diet, gastrointestinal bleeding, hematuria, and hemolysis.

By far the most common cause of chronic iron deficiency in adolescents or adults severe enough to cause anemia is excessive blood loss. In men, this is usually from the gastrointestinal (GI) tract. In women it may be either GI or vaginal bleeding. It has been estimated that 20%-50% of women in the menstrual age group have some degree of iron deficiency; menstrual loss is frequently aggravated by poor diet. Therefore, careful inquiry about the frequency, duration, and quantity of menstrual bleeding is essential in treating women. An estimate of quantity may be made from the number of menstrual pads used. GI bleeding is most frequently due to peptic ulcer in men and women below age 40. After age 40 GI carcinoma is more common and should always be ruled out. Hemorrhoids are sometimes the cause of chronic iron deficiency anemia, but since hemorrhoids are common it should never be assumed that the anemia is due only to hemorrhoids.

If excessive vaginal bleeding is suspected, a careful vaginal/uterine examination with a Papanicolaou smear should be done. If necessary, a gynecologist should be consulted. For possible GI bleeding an occult blood test on a stool sample should be ordered on at least three separate days. However, one or more negative stool guaiac results do not rule out GI cancer or peptic ulcer, since these lesions may bleed intermittently. If a patient is over age 40 and stool guaiac results are negative, many gastroenterologists recommend a barium enema and possibly sigmoidoscopy or colonoscopy. If the barium enema or endoscopy result is negative, and no other cause for the iron deficiency anemia can be demonstrated, they recommend repeating the barium enema in 3-4 months in case a lesion was missed. Lower GI tract studies are particularly important for detection of carcinoma because colon carcinoma has an excellent cure rate if discovered in its early stages. Gastric carcinoma, on the other hand, has a very poor cure rate by the time it becomes demonstrable. In addition to peptic ulcer, gastric hiatal hernia is sometimes associated with iron deficiency anemia.