Iron Deficiency

Marked alterations (either increased or decreased) in the red cell indices almost always reflect a maturation defect or iron deficiency. Iron deficiency is revealed by a low serum iron, low percent transferrin saturation, and low serum ferritin. A microcytic anemia in the presence of normal iron values suggests a defect (most commonly inherited) in Hb synthesis.

In most medical practices, the identification of iron deficiency should be foremost, since it may be associated with occult bleeding or other serious conditions, and it can be quickly and easily treated with iron supplementation. Other less common but reversible anemias include vitamin B12 and folate deficiency, and some cases of anemia associated with inflammation. Each of these requires a slightly different therapeutic approach.

Iron deficiency in adult males and postmenopausal females must be considered due to chronic blood loss until proven otherwise. There are a variety of oral and parenteral iron preparations to choose from in treating iron deficiency. For most uncomplicated cases, an oral iron preparation will suffice. A total elemental iron dose of 200 mg/day will gradually reverse the iron deficiency anemia. Oral iron should be continued for some months after the reversal of the anemia in order to replenish body iron stores. A convenient rule of thumb is to continue iron replacement for 6 months after correction of the anemia. If oral iron is not absorbed well, or if the patient cannot tolerate the side effects of oral iron treatment, parenteral iron may be given.

When the serum iron falls (true iron deficiency or acute inflammation), Hb synthesis is impaired and microcytic, hypochromic red cells are produced. The serum ferritin reflects total body iron stores and is decreased in iron deficiency, but normal or increased in states of acute or chronic inflammation. This is a useful laboratory test to distinguish between true iron deficiency and chronic inflammatory states.

Although any type of anemia may be seen in patients with RA, the two primary types of anemia in RA appear to be iron deficiency anemia and anemia of chronic disease. In their retrospective review of 225 patients with RA, Peeters and colleagues identified 64% as anemic. Of the group classified as anemic, 77% were found to have anemia of chronic disease and 23% to have iron deficiency anemia.19

Differential diagnosis may be difficult, as serum iron levels are low in both types of anemia, and bone marrow staining for iron stores may be required. However, serum ferritin testing usually distinguishes between iron deficiency and anemia of chronic disease. Patients with serum ferritin levels >50 µg/mL are likely to have anemia of chronic disease, while those with a lower value of serum ferritin are likely to be iron deficient.22-24

The most common causes of iron deficiency anemia in RA are blood loss through menstrual bleeding and/or gastrointestinal bleeding secondary to nonsteroidal anti-inflammatory drugs. Anemia of chronic disease is an “inflammatory anemia,” and its features in RA are similar to those seen in inflammatory bowel disease, HIV, aging, and cancer.

Iron-deficiency Anemia Common During Long-term Total Parenteral Nutrition

LOS ANGELES (National Anemia Action Council) - Patients receiving long-term home total parenteral nutrition (HPN) should be routinely screened for iron-deficiency anemia, Massachusetts investigators recommend. If iron deficiency is detected, regular administration of low-dose iron is safer than total dose infusion, they have found.

Only 13 of the 30 patients with iron-deficiency anemia had episodes of acute blood loss. The researchers note in their paper that each milliliter of blood contains 0.5 mg of iron, so "even minor chronic blood loss can be clinically important."

In 10 of the patients, iron-deficiency anemia was diagnosed when HPN was initiated. In the others it developed two to 97 months later (mean 28.8 months).

"For the first year after initiation of total parenteral nutrition, iron studies should be done every 3 months," Dr. Bistrian's group suggests. "If no problem is found during that examination, yearly assessment is sufficient. If iron deficiency is found, treatment should be proposed and monitored every 3 months until a stable iron regimen is defined, and then monitored every 6 months thereafter."

Twenty of the patients with iron-deficiency anemia received IV iron rather than a blood transfusion or oral iron supplementation. Of these, eight received iron doses of 100 to 500 mg by total dose infusion or multiple infusions; seven received low doses of iron in HPN, 10 mg to 75 mg at a time for up to 6 months; and five were treated with both regimens.

Rash, urticaria, and/or shortness of breath developed in four of the 13 patients who received total dose infusion, the authors report. Low-dose iron was not associated with such events. One patient with shortness of breath after total dose infusion subsequently responded well to repeated dosing with 10 mg of iron in HPN. Total dose infusion is "a perfectly acceptable therapy," Dr. Bistrian said. "But you're a little more likely, if you give large doses, 400 or 500 milligrams, to have mild, self-limited symptoms from it. If you give less than 75 milligrams, there's really no reaction."

"And occasionally, less than 1% of the time, you'll get a severe reaction with a total dose infusion," Dr. Bistrian continued. "To my knowledge it's not been shown with low-dose infusions that you can get anaphylactic reactions that are very severe."

He pointed out that most people who develop iron-deficiency anemia have an ongoing loss and require iron permanently. "To us it's more reasonable to find out how much more iron they need and just give it to them all the time, rather than give them a big dose. As they get further and further away from the dose, they redevelop the anemia."

In their report, Dr. Bistrian and his associates share their method of estimating how much iron should be replaced. They determine "the iron equivalent of rate of hematocrit or hemoglobin drop over time by means of the following equation: iron (mg) = 0.3 x weight (lbs) [100 (actual Hb (g/dL) 100/desired Hb]."