Iron Deficiency : Part 5

by CDC

(Page 5 of 11)

Tests Used To Assess Iron Status

Iron status can be assessed through several laboratory tests. Because each test assesses a different aspect of iron metabolism, results of one test may not always agree with results of other tests. Hematological tests based on characteristics of red blood cells (i.e., Hb concentration, hematocrit, mean cell volume, and red blood cell distribution width) are generally more available and less expensive than are biochemical tests. Biochemical tests (i.e., erythrocyte protoporphyrin concentration, serum ferritin concentration, and transferrin saturation), however, detect earlier changes in iron status.

Although all of these tests can be used to assess iron status, no single test is accepted for diagnosing iron deficiency. Detecting iron deficiency in a clinical or field setting is more complex than is generally believed.

Lack of standardization among the tests and a paucity of laboratory proficiency testing limit comparison of results between laboratories. Laboratory proficiency testing is currently available for measuring Hb concentration, hematocrit, red blood cell count, serum ferritin concentration, and serum iron concentration; provisional proficiency testing was added in 1997 for total iron-binding capacity in the College of American Pathologists survey and was added to the American Association of Bioanalysts survey in 1998. As of April 1998, three states (New York, Pennsylvania, and Wisconsin) had proficiency testing programs for erthrocyte protoporphryin concentration. Regardless of whether test standardization and proficiency testing become routine, better understanding among health-care providers about the strengths and limitations of each test is necessary to improve screening for and diagnosis of iron-deficiency anemia, especially because the results from all of these tests can be affected by factors other than iron status.

Only the most common indicators of iron deficiency are described in this section. Other indicators of iron deficiency (e.g., unbound iron-binding capacity and the concentrations of transferrin receptor, serum transferrin, and holo-ferritin) are less often used or are under development. Hb Concentration and Hematocrit

Because of their low cost and the ease and rapidity in performing them, the tests most commonly used to screen for iron deficiency are Hb concentration and hematocrit (Hct). These measures reflect the amount of functional iron in the body. The concentration of the iron-containing protein Hb in circulating red blood cells is the more direct and sensitive measure. Hct indicates the proportion of whole blood occupied by the red blood cells; it falls only after the Hb concentration falls. Because changes in Hb concentration and Hct occur only at the late stages of iron deficiency, both tests are late indicators of iron deficiency; nevertheless, these tests are essential for determining iron-deficiency anemia.

Because iron deficiency is such a common cause of childhood anemia, the terms anemia, iron deficiency, and iron-deficiency anemia are often used interchangeably. The only cases of anemia that can be classified as iron-deficiency anemia, however, are those with additional evidence of iron deficiency. The concept of a close association between anemia and iron deficiency is closest to correct when the prevalence of iron deficiency is high. In the United States, the prevalence and severity of anemia have declined in recent years; hence, the proportion of anemia due to causes other than iron deficiency has increased substantially. As a consequence, the effectiveness of anemia screening for iron deficiency has decreased in the United States.

Iron deficiency may be defined as absent bone marrow iron stores (as described on bone marrow iron smears), an increase in Hb concentration of greater than 1.0 g/dL after iron treatment, or abnormal values on certain other biochemical tests. The recent recognition that iron deficiency seems to have general and potentially serious negative effects has made identifying persons having iron deficiency as important as identifying persons having iron-deficiency anemia.

The case definition of anemia recommended in this report is less than 5th percentile of the distribution of Hb concentration or Hct in a healthy reference population and is based on age, sex, and (among pregnant women) stage of pregnancy. This case definition for anemia was shown to correctly identify 37% of women of childbearing age and 25% of children aged 1-5 years who were iron deficient (defined as two of three positive test results {i.e., low mean cell volume, high erythrocyte protoporphyrin, or low transferrin saturation}) (sensitivity) and to correctly classify 93% of women of childbearing age and 92% of children aged 1-5 years as not having iron deficiency (specificity). Lowering the Hb concentration or Hct cut-off would result in identifying fewer people who have anemia due to causes other than iron deficiency (false positives) but also in overlooking more people with iron deficiency (true positives).

The distributions of Hb concentration and Hct and thus the cutoff values for anemia differ between children, men, nonpregnant women, and pregnant women and by age or weeks of gestation. The distributions also differ by altitude, smoking status, and race.

Among pregnant women, Hb concentration and Hct decline during the first and second trimesters because of an expanding blood volume. Among pregnant women who do not take iron supplements, Hb concentration and Hct remain low in the third trimester, and among pregnant women who have adequate iron intake, Hb concentration and Hct gradually rise during the third trimester toward the prepregnancy levels. Because adequate data are lacking in the United States, the cutoff values for anemia are based on clinical studies of European women who had taken iron supplementation during pregnancy. For pregnant women, a test result greater than 3 standard deviations (SD) higher than the mean of the reference population (i.e., a Hb concentration of greater than 15.0 g/dL or a Hct of greater than 45.0%), particularly in the second trimester, likely indicates poor blood volume expansion. High Hb concentration or Hct has been associated with hypertension and poor pregnancy outcomes (e.g., fetal growth retardation, fetal death, preterm delivery, and low birthweight). In one study, women who had a Hct of greater than or equal to 43% at 26-30 weeks' gestation had more than a twofold increased risk for preterm delivery and a fourfold increased risk for delivering a child having fetal growth retardation than did women who had a Hct of 33%-36%. Hence, a high Hb concentration or Hct in the second or third trimester of pregnancy should not be considered an indicator of desirable iron status.

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