Laboratory Assessment of Iron Deficiency
Diagnosis of iron deficiency in most patients can be made based on the measurement
of a low serum iron and low serum ferritin with an elevated total iron binding capacity
(TIBC). Serum ferritin and stainable iron in tissue stores
decrease even in the early stages of iron deficiency, as iron stores become depleted.7 Other parameters such as transferrin saturation (TSAT)
and free erythrocyte protoporphyrin do not reach abnormal levels until tissue iron
stores are completely depleted. Only when iron stores
are insufficient for heme synthesis (ie, iron deficiency anemia) do hemoglobin levels
and red cell indices begin to decrease (Figure 1).
A low serum ferritin (<12 ng/mL) is virtually diagnostic of iron deficiency;
however, an elevated serum ferritin level does not necessarily imply that iron stores
are adequate. Serum ferritin can serve as a surrogate
marker for iron stores, but it is also an acute-phase reactant and its levels may
be elevated under conditions of chronic inflammation, liver disease, or malignancy,
independent of iron status. Infection and systemic inflammation
can induce secretion of hepcidin by the liver, which leads to sequestration of iron
within storage sites and reduced intestinal absorption of iron.
Thus, iron stores may be sufficient but may not be available for erythropoiesis.
Under these conditions, serum iron is low, iron-binding capacity is low to normal,
but serum ferritin may be normal to high. Therefore,
in patients with inflammation, infection, or malignancy, serum ferritin may not
be a reliable indicator of iron status.
Stainable tissue iron
The absence of stainable iron on a bone marrow aspirate that contains spicules is
diagnostic of iron deficiency. However, bone marrow aspiration
is an invasive and costly procedure and has been largely replaced by performance
of serum iron, TIBC, and serum ferritin measurements on blood samples.
Serum iron and TIBC measurements
Iron is carried to the bone marrow by transferrin, which is an iron-transport protein
that is found in plasma. Serum iron levels measure transferrin-bound iron. TIBC,
or total iron binding capacity, measures the amount of circulating transferrin that
is available to bind iron.
Transferrin is a protein whose primary function is to transport iron from iron storage
sites in the reticuloendothelial system to the bone marrow for use in erythropoiesis.
Transferrin saturation (TSAT) is defined as the ratio of serum iron to the total
iron-binding capacity (TIBC, a measure of circulating transferrin) x 100.
Serum iron x 100
TSAT indicates the percentage of binding sites on transferrin that are occupied
by iron and is therefore a measure of circulating iron that is immediately available
for erythropoiesis. A reduction in TSAT suggests an inadequate supply of iron to
the developing erythrocyte. However, a reduced TSAT does not always indicate iron
deficiency since other disorders can cause iron deficient erythropoiesis.
Hemoglobin is the iron-containing protein that carries oxygen to the various tissues
of the body. Hemoglobin values represent the total amount of hemoglobin in grams
per 100 mL of blood. Measurement of hemoglobin is convenient, simple, and inexpensive
to obtain. The hemoglobin level provides a quantitative
measure of the severity of iron deficiency, but only after anemia has developed.28
Hemoglobin levels decrease to below-normal only after iron stores have been depleted
and heme synthesis is impaired. As an index of iron deficiency, hemoglobin has low
specificity since various other conditions, such as malnutrition, hemoglobinopathies,
and chronic infections can also cause a decrease in erythropoiesis.
It also has a low sensitivity due to overlap of values between patients with and
without iron deficiency.
Soluble serum transferrin receptor (sTfR)
With iron deficiency, eythroblasts in the bone marrow will increase the presentation
of membrane transferrin receptor. If a patient is not receiving sufficient iron
and erythropoiesis is being stimulated by an erythropoiesis-stimulating agent, then
increased transferrin receptors will become expressed on the erythroblasts, some
of which come off and will be detectable in the circulation. The sTfR correlates
with this membrane expression of the transferrin receptor and also tends to be elevated
in the presence of increased erythroid activity. Some
studies indicate that soluble transferrin receptor level may not be affected by
inflammation of liver disease and so can be used to identify iron deficiency anemia
under conditions of inflammation or liver disease. However,
measurement of sTfr is not routinely performed in most centers.
| ||Normal||Iron Depletion||Prelatent Iron Deficiency||Latent Iron Deficiency||Iron Deficient Erythropoiesis||Early Iron Deficiency Anemia||Late Iron Deficiency Anemia|
|Serum Ferritin (μg/l)||60||20||<12||<12||<12||<12||<12|
|Stainable Tissue Iron (0-4+)||2+||1+||0||0||0||0||0|
|Transferrin Saturation (%)||35||35||35||20||<16||<16||<16|
|Free Erythrocyte Protoporphyrin (μg/dl)||30||30||30||75||>100||>100||>100|
|Mean Corpuscular Volume (μ3)||90||90||90||90||88||86||<82|
|Mean Corpuscular Hemoglobin Concentration (0/0)||33||33||33||33||33||31||<28|
Figure 1: Laboratory measurements during gradual progression of iron deficiency
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INFeD is indicated in the treatment of patients with documented iron deficiency in whom oral administration is unsatisfactory or impossible.
Important Safety Information
Anaphylactic-type reactions, including fatalities, have followed the parenteral administration of iron dextran injection. A test dose should be administered prior to the first therapeutic dose, followed by the full therapeutic dose if no signs or symptoms of anaphylactic-type reactions are seen. Resuscitation equipment and personnel trained in the detection and treatment of anaphylactic-type reactions must be readily available during all INFeD administrations. Patients should be observed for signs or symptoms of anaphylactic-type reactions during all INFeD administrations. Fatal reactions have followed the test dose and have also occurred in situations where the test dose was tolerated. Use INFeD only in patients in whom clinical and laboratory investigations have established an iron deficient state not amenable to oral iron therapy. Patients with a history of drug allergy or multiple drug allergies may be at increased risk of anaphylactic-type reactions. INFeD should be used with caution in individuals with histories of significant allergies and/or asthma, and is contraindicated in patients with hypersensitivity to the product and patients with all anemias not associated with iron deficiency. INFeD should be used with extreme care in patients with serious impairment of liver function, and should not be used during the acute phase of infectious kidney disease. Unwarranted therapy with parenteral iron will cause excess storage of iron with the consequent possibility of exogenous hemosiderosis, which is particularly apt to occur in patients with hemoglobinopathies and other refractory anemias.