Transferrin and Iron-binding Capacity (TIBC, UIBC)
When you have low hemoglobin and hematocrit on a complete blood count (CBC); when your healthcare practitioner suspects you may have too much iron (overload) or too little iron (deficiency) in the body
A blood sample drawn from a vein in your arm
You may be instructed to have your blood drawn in the morning and/or fast for 12 hours before the test; in this case, only water is allowed. Follow any instructions from your healthcare practitioner and/or from the laboratory performing the test.
Transferrin is the main protein in the blood that binds to iron and transports it throughout the body. A transferrin test directly measures the level in the blood. Alternatively, transferrin may be measured indirectly (or converted by calculation) so that its level is expressed as the amount of iron it is capable of binding. This is called the total iron binding capacity (TIBC).
Iron is an essential nutrient that, among other functions, is necessary for the production of healthy red blood cells (RBCs). It is a critical part of hemoglobin, the protein in RBCs that binds oxygen in the lungs and releases oxygen as blood circulates to other parts of the body. The body cannot produce iron and must absorb it from the foods we eat or from supplements.
Normally, iron is transported throughout the body by transferrin, which is produced by the liver. In healthy people, most iron is incorporated into the hemoglobin within RBCs. The remainder is stored in the tissues as ferritin or hemosiderin, with additional small amounts used for other purposes (e.g., to produce other proteins such as myoglobin and some enzymes).
The transferrin test, TIBC, UIBC, and transferrin saturation, along with other iron tests, help evaluate the amount of iron in the body by measuring several substances in the blood. These tests are often ordered at the same time and the results interpreted together to help diagnose and/or monitor iron deficiency or iron overload.
- Serum iron test—measures the total amount of iron in the liquid portion of the blood, nearly all of which is bound to transferrin.
- Transferrin test—directly measures the level of transferrin in the blood. The level depends upon liver function and a person's nutritional status. Transferrin is a protein that may decrease during any inflammatory process and is referred to as a negative acute phase reactant.
- TIBC (total iron-binding capacity)—measures the total amount of iron that can be bound by proteins in the blood. Since transferrin is the primary iron-binding protein, the TIBC test is a good indirect measurement of transferrin availability—the amount of transferrin that is available to bind to iron. (Note: Though TIBC is a reflection of the amount of transferrin available, TIBC and transferrin are not synonymous.)
- UIBC (unsaturated iron-binding capacity)—this test determines the reserve capacity of transferrin, i.e., the portion of transferrin that has not yet been saturated with iron.
- Transferrin saturation— dividing the iron concentration by the TIBC produces an estimate of how many of transferrin iron-binding sites are occupied; this is called the transferrin saturation. Under normal conditions, transferrin is typically one-third saturated with iron. This means that about two-thirds of its capacity is held in reserve. (Less commonly, the iron concentration may be divided by the transferrin concentration, not the TIBC. This similar estimate is usually called the transferrin index.)
- Ferritin—measures the level of ferritin, a protein made by almost all cells in response to increased iron. The ferritin level reflects the total body iron. It will be low when there is iron deficiency and high when there is an excess of iron in the body.
When the level of iron is insufficient to meet the body's needs, the level of iron in the blood drops and iron stores are depleted. This may occur because:
- There is an increased need for iron, for example during pregnancy or childhood, or due to a condition that causes chronic blood loss (e.g., peptic ulcer, colon cancer)
- Not enough iron is consumed (either foods or supplements)
- The body is unable to absorb iron from the foods eaten in conditions such as celiac disease
Insufficient levels of circulating and stored iron may eventually lead to iron deficiency anemia (decreased hemoglobin and hematocrit, smaller and paler red cells). In the early stage of iron deficiency, no physical effects are usually seen and the amount of iron stored may be significantly depleted before any signs or symptoms of iron deficiency develop. If a person is otherwise healthy and anemia develops over a long period of time, symptoms may not appear before the hemoglobin in the blood drops below the lower limit of normal.
However, as the iron deficiency progresses, symptoms eventually begin to appear. The most common symptoms of anemia include fatigue, weakness, dizziness, headaches and pale skin. Read the article on Anemia to learn more.
Conversely, too much iron can be toxic to the body. Iron storage and ferritin levels increase when more iron is absorbed than the body needs. Absorbing too much iron over time can lead to the progressive buildup of iron compounds in organs and may eventually cause their dysfunction and failure. An example of this is hemochromatosis, a rare genetic disease in which the body absorbs and builds up too much iron, even on a normal diet. Additionally, iron overload can occur when a person undergoes repeated blood transfusions.
How is it used?
The transferrin, total iron-binding capacity (TIBC) or unsaturated iron-binding capacity (UIBC) test may be used along with other iron tests to assess the amount of iron circulating in the blood, the total capacity of the blood to transport iron, and the amount of stored iron in the body. Testing may also help differentiate various causes of anemia.
Iron tests are often ordered together, and the results of each can help identify iron deficiency, iron deficiency anemia, or too much iron in the body (overload).
When is it ordered?
These tests may be ordered along with other iron tests when results from a routine complete blood count (CBC) show that a person's hemoglobin and hematocrit are low and their red blood cells are smaller and paler than normal (microcytic and hypochromic), suggesting iron deficiency anemia even though other clinical symptoms may not have developed yet.
- Chronic fatigue/tiredness
- Pale skin (pallor)
Testing may be ordered when iron overload is suspected. Signs and symptoms of iron overload will vary from person to person and tend to worsen over time. They are due to iron accumulation in the blood and tissues. These may include:
- Joint pain
- Fatigue, weakness
- Weight loss
- Lack of energy
- Abdominal pain
- Loss of sex drive
- Organ damage, such as in the heart and/or liver
Testing is also ordered when there is a case of suspected iron poisoning. This is most common in children who accidentally overdose with vitamins or other supplements containing iron.
What does the test result mean?
The results of transferrin tests, TIBC, or UIBC are usually evaluated in conjunction with other iron tests. A summary of the changes in iron tests seen in various diseases of iron status is shown in the table below.
Disease Iron TIBC/Transferrin UIBC
Ferritin Iron Deficiency Low High High Low Low Hemochromatosis/Hemosiderosis High Low Low High High Chronic Illness Low Low/Normal Low/Normal Low/Normal High/Normal Hemolytic Anemia High Normal/Low Low/Normal High High Sideroblastic Anemia Normal/High Normal/Low Low/Normal High High Iron Poisoning High Normal Low High Normal
The early stage of iron deficiency is the slow depletion of iron stores. This means there is still enough iron to make red cells but the stores are being used up without adequate replacement. The serum iron level may be normal in this stage, but the ferritin level will be low.
As iron deficiency continues, all of the stored iron is used and the body tries to compensate by producing more transferrin to increase iron transport. The serum iron level continues to decrease and transferrin and TIBC and UIBC increase. As this stage progresses, fewer and smaller red blood cells are produced, eventually resulting in iron deficiency anemia. Transferrin saturation is decreased with iron deficiency.
If the iron level and transferrin saturation are high, the TIBC, UIBC and ferritin are normal and the person has a clinical history consistent with iron overdose, then it is likely that the person has iron poisoning. Iron poisoning occurs when a large dose of iron is taken all at once (acute) or over a long period of time (chronic). Iron poisoning in children is almost always acute, occurring in children who ingest their parents' iron supplements. In some cases, acute iron poisoning can be fatal.
A person who has mutations in the HFE gene is diagnosed with hereditary hemochromatosis. However, while many people who have hemochromatosis will have no symptoms for their entire life, others will start to develop symptoms such as joint pain, abdominal pain, and weakness in their 30's or 40's. Men are affected more often than women because women lose blood during their reproductive years through menstruation.
Iron overload may also occur in people who have hemosiderosis and in those who have had repeated transfusions. This may occur with sickle cell anemia, thalassemia major, or other forms of anemia. The iron from each transfused unit of blood stays in the body, eventually causing a large buildup in the tissues. Some persons with alcoholism and with chronic liver disease also develop iron overload.
Is there anything else I should know?
Recent blood transfusions can affect test results as can iron injections or transfused iron. Multiple blood transfusions can sometimes lead to iron overload.
A high TIBC, UIBC, or transferrin usually indicates iron deficiency, but they are also increased in pregnancy and with the use of oral contraceptives.
How is transferrin saturation calculated?
The calculation is:
Transferrin saturation (%) = (Serum iron level x 100%) / TIBC
TIBC measures the total amount of iron that can be bound by proteins in the blood. Since transferrin is the primary iron-binding protein, the TIBC test is a good indirect measurement of transferrin availability—the amount of transferrin that is available to bind to iron.
In healthy individuals, transferrin is one-third saturated with iron. This means that there is about two-thirds held in reserve. In iron deficiency, all of the stored iron is used and the body tries to compensate by producing more transferrin to increase iron transport. While the serum iron level continues to decrease, the transferrin level increases. Thus, the amount of transferrin available to bind iron (TIBC) increases and the amount of transferrin saturated with iron (i.e., percent transferrin saturation) decreases.
What other factors affect the transferrin level?
Transferrin is a protein that may decrease during any inflammatory process and is referred to as a negative acute phase reactant. Chronic inflammation, infections, and malignancies may cause changes in transferrin levels.
Are there other things that cause anemia besides iron-deficiency?
Yes, there are numerous causes of anemia. However, iron deficiency is one of the most common. If iron tests rule out iron deficiency, another source for the anemia must be found. See the article on Anemia for more on this.