Iron Deficiency Anemia

Anemia can be caused by iron deficiency, folate deficiency, vitamin B₁₂ deficiency, and other causes. The term iron deficiency anemia means anemia that is due to iron deficiency. Iron deficiency anemia is characterized by the production of small red blood cells. When examined under a microscope, the red blood cells also appear pale or light-colored. For this reason, the anemia that occurs with iron deficiency is also called hypochromic microcytic anemia.

Description

Iron deficiency anemia is the most common type of anemia throughout the world. In the United States, iron deficiency anemia occurs to a lesser extent than in developing countries because of the higher consumption of red meat and the practice of food fortification (addition of iron to foods by the manufacturer). Anemia in the United States is caused by a variety of sources, including excessive losses of iron in menstrual fluid and excessive bleeding in the gastrointestinal tract. In developing countries located in tropical climates, the most common cause of iron deficiency anemia is infestation with hookworm.

Causes and symptoms

Infancy is a period of increased risk for iron deficiency. The human infant is born with a built-in supply of iron, which can be tapped during periods of drinking low-iron milk or formula. Both human milk and cow milk contain rather low levels of iron (0.5–1.0 mg iron/liter). However, the iron in human milk is about 50% absorbed by the infant, while the iron of cow milk is only 10% absorbed. During the first six months of life, growth of the infant is made possible by the milk in the diet and by the infant's built-in supply. However, premature infants have a lower supply of iron and, for this reason, it is recommended that preterm infants (beginning at two months of age) be given oral supplements of 7 mg iron/day, as ferrous sulfate. Iron deficiency can be provoked where infants are fed formulas that are based on unfortified cow milk. For example, unfortified cow milk is given free of charge to mothers in Chile. This practice has the fortunate result of preventing general malnutrition, but the unfortunate result of allowing the development of mild iron deficiency.

The normal rate of blood loss in the feces is 0.5–1.0 ml per day. These losses can increase with colorectal cancer. About 60% of colorectal cancers result in further blood losses, where the extent of blood loss is 2–10 ml/day. Cancer of the colon and rectum can provoke losses of blood, resulting in iron deficiency anemia. The fecal blood test is widely used to screen for the presence of cancer of the colon or rectum. In the absence of testing, colorectal cancer may be first detected because of the resulting iron deficiency anemia.

Infestation with hookworm can provoke iron deficiency and iron deficiency anemia. The hookworm is a parasitic worm. It thrives in warm climates, including the southern United States. The hookworm enters the body through the skin, through the soles of bare feet. The hookworm then migrates to the small intestines where it attaches itself to the villi (small sausage-shaped structures in the intestines that are used for the absorption of all nutrients). The hookworm damages the villi, resulting in blood loss, and they produce anti-coagulants that promote continued bleeding. Each worm can provoke the loss of up to 0.25 ml of blood per day.

Bleeding and blood losses through gastrointestinal tract can be provoked by colorectal cancer and hookworms, as mentioned above, but also by hemorrhoids, anal fissures, irritable bowel syndrome, aspirin-induced bleeding, blood clotting disorders, and diverticulosis (a condition caused by an abnormal opening from the intestine or bladder). Several genetic diseases exist that lead to bleeding disorders, and these include hemophilia A, hemophilia B, and von Willebrand's disease. Of these, only von Willebrand's disease leads to gastrointestinal bleeding.

The symptoms of iron deficiency anemia include weakness and fatigue. These symptoms result from dys-function of the red blood cells, and the reduced ability of the red blood cells to carry iron to exercising muscles. Iron deficiency can also affect other tissues, including the tongue and fingernails. Prolonged iron deficiency can result in changes of the tongue, and it may become smooth, shiny, and reddened. This condition is called glossitis. The fingernails may grow abnormally, and acquire a spoon-shaped appearance.

Decreased iron intake is a contributing factor in iron deficiency and iron deficiency anemia. The iron content of cabbage, for example, is about 1.6 mg/kg food, while those of spinach (33 mg/kg), lima beans (15 mg/kg), potato (14 mg/kg), tomato (3 mg/kg), apples (1.5 mg/kg), raisins (20 mg/kg), whole wheat bread (43 mg/kg), eggs (20 mg/kg), canned tuna (13 mg/kg), chicken (11 mg/kg), beef (28 mg/kg), corn oil (0.6 mg/kg), and peanut butter(6.0 mg/kg), are indicated. One can see that apples, tomatoes, and vegetable oil are relatively low in iron, while whole wheat bread and beef are relatively high in iron. The assessment of whether a food is low or high in iron can also be made by comparing the amount of that food eaten per day with the recommended dietary allowance (RDA) for iron. The RDA for iron for the adult male is 10 mg/day, while that for the adult woman is 15 mg/day. The RDA during pregnancy is 30 mg/day. The RDA for infants of 0–0.5 years of age is 6 mg/day, while that for infants of 0.5–1.0 years of age is 10 mg/day. The RDA values are based on the assumption that the consumer eats a mixture of plant and animal foods.

The above list of iron values alone may be deceptive, since the availability of iron in fruits, vegetables, and grains is very low, while the availability from meat is much higher. The availability of iron in plants ranges from only 1–10%, while that in meat, fish, chicken, and liver is 20–30%. The term availability means the percent of dietary iron that is absorbed via the gastrointestinal tract to the bloodstream. Non-absorbed iron is lost in the feces.

Interactions between various foods can influence the absorption of dietary iron. Vitamin C can increase the absorption of dietary iron. Orange juice is a rich source of vitamin C. Thus, if a plant food, such as rice, is consumed with orange juice, then the orange juice can enhance the absorption of the iron in the rice. Vitamin C is also added to infant formulas, and the increased use of formulas fortified with both iron and vitamin C have led to a marked decline in anemia in infants and young children in the United States (Dallman, 1989). In contrast, if rice is consumed with tea, certain chemicals in the tea (tannins) can reduce the absorption of the iron. Phytic acid is a chemical that naturally occurs in legumes, cereals, and nuts. Phytic acid, which can account for 1–5% of the weight of these foods, is a potent inhibitor of iron absorption. The increased availability of the iron in meat products is partly due to the fact that heme-iron is absorbed to a greater extent than free iron salts, and to a greater extent than iron in the phytic acid/iron complex. Nearly all of the iron in plants is nonheme-iron. Much of the iron in meat is nonheme-iron as well. The nonheme-iron in meat, fish, chicken and liver may be about 20% available. The heme-iron of meat may be close to 30% available. The most available source of iron is human milk (50% availability).

Diagnosis

Iron deficiency anemia in infants is defined as a hemoglobin level below 109 mg/ml of whole blood, and a hematocrit below 33%. Anemia in adult males is defined as a hemoglobin under 130 mg/ml and a hematocrit below 38%. Anemia in adult females is defined as hemoglobin under 120 mg/ml and a hematocrit below 32%. Anemia in pregnant women is defined as hemoglobin of under 110 mg/ml and hematocrit below 31%.

When an abnormally high presence of blood is found in the feces during a fecal occult blood test, the physician needs to examine the gastrointestinal tract to determine the cause of bleeding. Here, the diagnosis for iron deficiency anemia includes an examination using a sigmoidoscope. The sigmoidoscope is an instrument that consists of a flexible tube that permits examination of the colon to a distance of 60 cm. A barium enema, with an x ray, may also be used to detect abnormalities that can cause bleeding.

The diagnosis of iron deficiency anemia should include a test for oral iron absorption, where evidence suggests that oral iron supplements fail in treating anemia. The oral iron absorption test is conducted by eating 64 mg iron (325 mg ferrous sulfate) in a single dose. Blood samples are then taken after two hours and four hours. The iron content of the blood serum is then measured. The concentration of iron should rise by an increment of about 22 micromolar, where iron absorption is normal. Lesser increases in concentration mean that iron absorption is abnormal, and that therapy should involve injections or infusions of iron.

Treatment

Oral iron supplements (pills) may contain various iron salts. These iron salts include ferrous sulfate, ferrous gluconate, or ferrous fumarate. Injections and infusions of iron can be carried out with a preparation called iron dextran. In patients with poor iron absorption (by the gut), therapy with injection or infusion is preferable over oral supplements. Treatment of iron deficiency anemia sometimes requires more than therapy with iron. Where iron deficiency was provoked by hemorrhoids, surgery may prove essential to prevent recurrent iron deficiency anemia. Where iron deficiency is provoked by bleeding due to aspirin treatment, aspirin should be discontinued. Where iron deficiency is provoked by hookworm infections, therapy for this parasite should be used, along with protection of the feet by wearing shoes whenever walking in hookworm-infested soil.

Prognosis

The prognosis for treating and curing iron deficiency anemia is excellent. Perhaps the main problem is failure to take iron supplements. In cases of pregnant women, the health care worker may recommend taking 100–200 mg iron/day. This dose is rather high, and can lead to nausea, diarrhea, or abdominal pain in 10–20% of women taking this dose. The reason for using this high dose is to effect a rapid cure for anemia, where the anemia is detected at a midpoint during the pregnancy. The above problems of side effects and noncompliance can be avoided by taking iron doses (100–200 mg) only once a week, where supplements are initiated some time prior to conception, or continuously throughout the fertile period of life. The problem of compliance is not an issue where infusions are used; however, a fraction of patients treated with iron infusions experience side effects, such as flushing, headache, nausea, anaphylaxis, or seizures. A number of studies have shown that iron deficiency anemia in infancy can result in reduced intelligence, where intelligence was measured in early childhood. It is not certain if iron supplementation of children with reduced intelligence, due to iron deficiency anemia in infancy, has any influence in allowing a "catch-up" in intellectual development.

Prevention

In the healthy population, all of the mineral deficiencies can be prevented by the consumption of inorganic nutrients at levels defined by the RDA. Iron deficiency anemia in infants and young children can be prevented by the use of fortified foods. Liquid cow milk-based infant formulas are generally supplemented with iron (12 mg/L). The iron in liquid formulas is added as ferrous sulfate or ferrous gluconate. Commercial infant cereals are also fortified with iron, and here small particles of elemental iron are added. The levels used are about 0.5 gram iron/kg dry cereal. This amount of iron is about tenfold greater than that of the iron naturally present in the cereal.