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To detect iron deficiency anemia and distinguish it from anemia caused by chronic illness or inflammation
When iron deficiency anemia is suspected
A blood sample drawn from a vein in your arm
Soluble transferrin receptors are proteins found in blood that can be elevated with iron deficiency. This test measures the amount of soluble transferrin receptors to help detect and evaluate iron deficiency and aid in the diagnosis of iron deficiency anemia.
Iron is an essential nutrient absorbed from the diet. Transferrin is the main protein in the blood that binds to iron and carries it to tissues and cells throughout the body. About 80% of iron is transported to the bone marrow, where it is incorporated into the hemoglobin in red blood cells (RBCs), and the rest is mostly stored in other cells and tissues as ferritin and hemosiderin.
When transferrin binds to iron, they form a complex. These complexes bind to transferrin receptors found on the surface of cells and the iron is then transported into the cells. Transferrin receptors are cleaved from the surface of cells, enter the bloodstream, and become soluble transferrin receptors (sTfR).
The number of transferrin receptors found on the surface of cells correlates with the level of iron within cells. When the iron level drops, the cells produce more transferrin receptors. As more receptors are produced, more are cleaved from cell surfaces and enter the blood, increasing the level of soluble transferrin receptors. Thus, measuring the level of sTfR is one way of evaluating the amount of iron available in the body.
Red blood cells have a lifespan of about 120 days. Because of this, the bone marrow must continually produce new RBCs. If there is insufficient iron taken in through the diet and/or increased iron loss (e.g., bleeding), iron reserve stored in the body is decreased. Over time, this can lead to iron deficiency, as the amount of iron stored in the body exhausts and the demand for iron exceeds the supply. As a result, fewer RBCs are produced and those newly formed RBCs are also smaller (microcytic) and contain less hemoglobin (hypochromic). This is a condition called iron deficiency anemia.
Usually, a ferritin test is used to evaluate the amount of iron reserve in the body and to help diagnose iron deficiency anemia. However, the ferritin level can be elevated when an individual has inflammation or a chronic disease, such as autoimmune disorders or some cancers. In these conditions, the ferritin test is not useful as it may falsely indicate adequacy in iron reserve and therefore a test for soluble transferrin receptors may be ordered.
The soluble transferrin receptor (sTfR) test is primarily ordered to help distinguish between anemia that is caused by iron deficiency and anemia that is caused by inflammation or a chronic illness (so-called anemia of chronic disease or inflammation). It is not a routine test but may be ordered if other tests that evaluate the amount of iron in the body do not provide conclusive information.
Typically, a group of iron tests is ordered to evaluate iron availability if a person has anemia and/or if iron deficiency is suspected. These tests may include iron, transferrin, TIBC (total iron-binding capacity, which is either measured or calculated based on the level of transferrin), transferrin saturation (calculated based on levels of iron and TIBC), and ferritin.
Ferritin is usually the preferred test to evaluate stored iron, but it is an acute phase reactant, which means that it may be increased with inflammation or with chronic diseases such as autoimmune disorders, some cancers, and chronic infections. In these cases, ferritin may not be a good measure of stored iron. Since sTfR is not an acute phase reactant, it may be ordered as an alternative to ferritin if a chronic illness is present or suspected.
The soluble transferrin receptor test is not routine but may be ordered along with or in follow up to other iron tests when you have a normal or near-normal ferritin level but iron deficiency is still suspected. It may be ordered as an alternative to ferritin when you have a chronic illness and/or inflammation is present or suspected.
This test may be ordered when you have general signs and symptoms of anemia, such as:
Or when you have signs and symptoms more specific for iron deficiency anemia, such as:
This test may also be ordered when a complete blood count (CBC) shows decreased hemoglobin and small red blood cells (low MCV).
The level of soluble transferrin receptor (sTfR) will be increased with iron deficiency. If you have anemia and your sTfR level is elevated, then it is likely that you have iron deficiency anemia. If your level is within the normal range, then it is more likely that the your anemia is due to another cause, such as chronic disease or inflammation.
If you are being treated for iron deficiency anemia, decreasing sTfR levels in a series of tests indicates an increase in iron reserve.
A low level of sTfR may be seen with hemochromatosis (a condition associated with iron overload) or protein malnutrition, but the test is not usually used to monitor these conditions.
African Americans may have moderately increased sTfR levels, as will people who live at higher elevations.
Birth control pills may affect the test results.
This testing may not be useful if you have an inherited disorder that affects hemoglobin production or function, such as thalassemia or sickle cell anemia. Test results may be elevated in people with red blood cell breakage (hemolysis) or recent blood loss and will not be accurate in those who have had a recent blood transfusion.
An elevated sTfR level is not as specific for iron deficiency as is, for example, a very low level of ferritin.
A single iron test does not provide the full picture of the amount of iron that you have stored and available. It is usually necessary to evaluate the results of several related iron tests together. Ferritin is usually the preferred test to evaluate stored iron, but it is an acute phase reactant, meaning that it may be increased with inflammation or chronic diseases, such as cystic fibrosis patients who often have inflammation or infections, as well as people with diabetes who are treated with insulin. In these cases, ferritin may not be a good measure of stored iron as it may falsely indicate adequacy in iron reserve. The soluble transferrin receptor test is not a routinely order test, but since it is not an acute phase reactant, it may be ordered as an alternative to ferritin to evaluate stored iron when a chronic illness is present or suspected.
Yes. Early deficiency usually will not cause any symptoms and when symptoms do emerge, they may be mild or nonspecific enough – such as fatigue – that they are attributed to something else.
Soluble transferrin receptor testing requires specialized equipment and is not offered by every laboratory. Your sample may be sent to a reference laboratory and it may take a few days for results to be available.
Test methods and reference (normal) ranges for sTfR will vary slightly from laboratory to laboratory. Your healthcare provider may prefer to send your samples to the same laboratory to make results more directly comparable.
You should consult with your healthcare provider first. If you are anemic and/or at risk of anemia, then supplements may be useful. Excess iron in the body can cause health problems.
Sources Used in Current Review
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Transferrin. University of Rochester Medical Center. Available online at https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=transferrin. Accessed May 2019.
Anemia of Chronic Disease. National Organization for Rare Disorders. Available online at https://rarediseases.org/rare-diseases/anemia-of-chronic-disease/. Accessed May 2019.
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