Indicators of Iron Deficiency and Anemia

Indicators of iron deficiency can be used to distinguish the degree of iron deficiency that exists across the spectrum from the depletion of body iron stores to frank anemia (Table 1). Indicator cutoffs vary by age, sex, race, and physiologic state (e.g., pregnancy),

Table 1 Indicators for assessing the progression of iron deficiency from depletion of iron stores to iron deficiency anemia

Stage of iron





Decline in storage

# Serum ferritin



Decreased circulating

# Serum iron


" Total iron binding


# Transferrin


Insufficient tissue iron

" Transferrin


Impaired heme

" Protoporphyrin/





Impaired red blood

# Hemoglobin

cell production

# Hematocrit

# Red blood cell


so using a proper reference is important when interpreting indicators of iron deficiency.

Serum ferritin is directly related to liver iron stores— a gold standard for iron deficiency that is infrequently used due to the invasive nature of the test. Different sources place the cutoff for serum ferritin concentrations indicative of depleted stores at 12 or 15 mg/l. Once iron stores are exhausted, serum ferritin is not useful for determining the extent of iron deficiency. Serum ferritin is also useful for diagnosing iron excess. A major limitation of serum ferritin is the fact that it acts as an acute phase reactant and therefore is mildly to substantially elevated in the presence of inflammation or infection, complicating its interpretation when such conditions exist.

Transferrin saturation is measured as the ratio between total serum iron (which declines during iron deficiency) and total iron binding capacity (which increases during iron deficiency). Typically, transferrin is approximately 30% saturated, and low transferrin saturation (<16%) is indicative of iron deficiency. Transferrin saturation concentrations higher than 60% are indicative of iron overload associated with hereditary hemochromatosis. The use of transferrin saturation to distinguish iron deficiency is limited because of marked diurnal variation and its lack of sensitivity as an indicator.

Elevated circulating TfRs are a sensitive indicator of the tissue demand for iron. Circulating TfR is not affected by inflammation, a limitation of other indicators of iron status. Furthermore, expressing TfR as a ratio with ferritin appears to distinguish with a great deal of sensitivity iron deficiency anemia from anemia of chronic disease, making this combined measure potentially very useful in settings in which these conditions coexist.

Elevated erythrocyte zinc protoporphyrin indicates iron-deficient erythropoiesis. Protoporphyrin concentrations may also be elevated by inflammation and lead exposure.

Finally, although hemoglobin concentrations or percentage hematocrit are not specific for iron deficiency, these measures are used most frequently as a proxy for iron deficiency in field settings because of their technical ease. Anemia is defined as a hemoglobin concentration of less than 110 g/l for those 6 months to 5 years old and for pregnant women, 115 g/l for those 5-11 years old, 120 g/l for nonpreg-nant females older than 11 years and for males 12-15 years old, or 130 g/l for males older than 15 years of age. Other measures of red blood cell characteristics include total red blood cell counts, mean corpuscular volume, and mean hemoglobin volume.

The choice of indicators and the strategy for assessment will depend on technical feasibility and whether a screening or survey approach is warranted. When more than 5% of a population is anemic, iron deficiency is considered a public health problem, and population-based surveys may be useful for assessing and monitoring the prevalence of iron deficiency. When anemia is less prevalent, screening for iron deficiency in high-risk groups or symptomatic individuals is a more efficient approach. Hemoglobin alone would be insufficient to diagnose iron deficiency in an individual, but hemoglobin distributions can offer clues as to the extent to which anemia is attributable to iron deficiency in a population. Preferred indicators, such as transferrin and/or ferritin, may not be feasible due to blood collection requirements, cost, or technical difficulty in a population survey, but they may be indispensable for characterizing iron status of a population subgroup or individual.

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