Iron Deficiency : Part 7

by CDC

(Page 7 of 11)

Erythrocyte Protoporphyrin Concentration

Erythrocyte protoporphyrin is the immediate precursor of Hb. The concentration of erythrocyte protoporphyrin in blood increases when insufficient iron is available for Hb production. A concentration of greater than 30 ug/dL of whole blood or greater than 70 ug/dL of red blood cells among adults and a concentration of greater than 80 ug/dL of red blood cells among children aged 1-2 years indicates iron deficiency. The normal range of erythrocyte protoporphyrin concentration is higher for children aged 1-2 years than for adults, but no consensus exists on the normal range for infants. The sensitivity of free erythrocyte protoporphyrin to iron deficiency (as determined by response to iron therapy) in children and adolescents aged 6 months-17 years is 42%, and the estimated specificity is 61%.

Infection, inflammation, and lead poisoning as well as iron deficiency can elevate erythrocyte protoporphyrin concentration. This measure of iron status has several advantages and disadvantages relative to other laboratory measures. For example, the day-to-day variation within persons for erythrocyte protoporphyrin concentration is less than that for serum iron concentration and transferrin saturation. A high erythrocyte protoporphyrin concentration is an earlier indicator of iron-deficient erythropoiesis than is anemia, but it is not as early an indicator of low iron stores as is low serum ferritin concentration. Inexpensive, clinic-based methods have been developed for measuring erythrocyte protoporphyrin concentration, but these methods can be less reliable than laboratory methods.

Serum Ferritin Concentration

Nearly all ferritin in the body is intracellular; a small amount circulates in the plasma. Under normal conditions, a direct relationship exists between serum ferritin concentration and the amount of iron stored in the body, such that 1 ug/L of serum ferritin concentration is equivalent to approximately 10 mg of stored iron. In the United States, the average serum ferritin concentration is 135 ug/L for men, 43 ug/L for women, and approximately 30 ug/L for children aged 6-24 months.

Serum ferritin concentration is an early indicator of the status of iron stores and is the most specific indicator available of depleted iron stores, especially when used in conjunction with other tests to assess iron status. For example, among women who test positive for anemia on the basis of Hb concentration or Hct, a serum ferritin concentration of less than or equal to 15 ug/L confirms iron deficiency and a serum ferritin concentration of greater than 15 ug/L suggests that iron deficiency is not the cause of the anemia. Among women of childbearing age, the sensitivity of low serum ferritin concentration (less than or equal to 15 ug/L) for iron deficiency as defined by no stainable bone marrow iron is 75%, and the specificity is 98%; when low serum ferritin concentration is set at less than 12 ug/L, the sensitivity for iron deficiency is 61% and the specificity is 100%. Although low serum ferritin concentration is an early indicator of low iron stores, it has been questioned whether a normal concentration measured during the first or second trimester of pregnancy can predict adequate iron status later in pregnancy.

The cost of assessing serum ferritin concentration and the unavailability of clinic-based measurement methods hamper the use of this measurement in screening for iron deficiency. In the past, methodological problems have hindered the comparability of measurements taken in different laboratories, but this problem may be reduced by proficiency testing and standardized methods. Factors other than the level of stored iron can result in large within-individual variation in serum ferritin concentration. For example, because serum ferritin is an acute-phase reactant, chronic infection, inflammation, or diseases that cause tissue and organ damage (e.g., hepatitis, cirrhosis, neoplasia, or arthritis) can raise its concentration independent of iron status. This elevation can mask depleted iron stores.

Transferrin Saturation

Transferrin saturation indicates the extent to which transferrin has vacant iron-binding sites (e.g., a low transferrin saturation indicates a high proportion of vacant iron-binding sites). Saturation is highest in neonates, decreases by age 4 months, and increases throughout childhood and adolescence until adulthood. Transferrin saturation is based on two laboratory measures, serum iron concentration and total iron-binding capacity (TIBC). Transferrin saturation is calculated by dividing serum iron concentration by TIBC and multiplying by 100 to express the result as a percentage:

Transferrin saturation (%) = {serum iron concentration (ug/dL)/TIBC (ug/dL)} x 100

Serum iron concentration is a measure of the total amount of iron in the serum and is often provided with results from other routine tests evaluated by automated, laboratory chemistry panels. Many factors can affect the results of this test. For example, the concentration of serum iron increases after each meal, infections and inflammations can decrease the concentration, and diurnal variation causes the concentration to rise in the morning and fall at night. The day-to-day variation of serum iron concentration within individuals is greater than that for Hb concentration and Hct.

TIBC is a measure of the iron-binding capacity within the serum and reflects the availability of iron-binding sites on transferrin. Thus, TIBC increases when serum iron concentration (and stored iron) is low and decreases when serum iron concentration (and stored iron) is high. Factors other than iron status can affect results from this test. For example, inflammation, chronic infection, malignancies, liver disease, nephrotic syndrome, and malnutrition can lower TIBC readings, and oral contraceptive use and pregnancy can raise the readings. Nevertheless, the day-to-day variation is less than that for serum iron concentration. TIBC is less sensitive to iron deficiency than is serum ferritin concentration, because changes in TIBC occur after iron stores are depleted.

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