Iron studies interpretation

Iron is an essential nutrient that, among other functions, is needed in small quantities to help form normal red blood cells. Iron is a critical part of hemoglobin (Hb), the protein in red blood cells that binds oxygen in the lungs and releases it 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. Heme iron is the easiest form of iron for the body to absorb. It is found in meats and eggs. Non-heme iron is found in a wide variety of plants and in iron supplements. Iron-rich sources include green leafy vegetables such as spinach, collard greens, and kale, wheat germ, whole grain breads and cereals, raisins, and molasses. If you have been diagnosed with iron deficiency anemia or you are pregnant or breast feeding, vitamin pills or tablets may be needed to provide extra iron. Ask your healthcare practitioner about the right supplement for you. The people who typically need iron supplements are pregnant women and those with documented iron deficiency. People should not take iron supplements before talking to their healthcare practitioner as excess iron can cause chronic iron overload. An overdose of iron pills can be toxic, especially to children.

Iron studies are used 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 studies 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).

Iron studies 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 level of iron in the liquid portion of the blood.
• Transferrin test directly measures the level of transferrin in the blood. Transferrin is the protein that transports iron around in the body. Under normal conditions, transferrin is typically one-third saturated with iron. This means that about two-thirds of its capacity is held in reserve.
• Total iron-binding capacity (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  (total iron-binding capacity) test is a good indirect measurement of transferrin availability.
• Unsaturated iron-binding capacity (UIBC). The unsaturated iron-binding capacity (UIBC) test determines the reserve capacity of transferrin, i.e., the portion of transferrin that has not yet been saturated with iron. UIBC (unsaturated iron-binding capacity) also reflects transferrin levels.
• Transferrin saturation is a calculation that reflects the percentage of transferrin that is saturated with iron (100 x serum iron/total iron-binding capacity).
• Serum ferritin reflects the amount of stored iron in the body.

Iron is normally absorbed from food in the small intestine and transported throughout the body by binding to transferrin, a protein produced by the liver. In healthy people, most of the iron transported is incorporated into the production of red blood cell hemoglobin. The remainder is stored in the tissues as ferritin or hemosiderin, with additional small amounts used to produce other proteins such as myoglobin and some enzymes.

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 seldom 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.

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 overdose can occur when someone consumes more than the recommended amount of iron.

A summary of the changes in iron studies seen in various diseases of iron status is shown in the table below.

Table 1. Iron studies interpretation table

Disease	Iron	TIBC/Transferrin	UIBC (unsaturated iron-binding capacity)	% Transferrin Saturation	Ferritin
Iron Deficiency	Low	High	High	Low	Low
Hemochromatosis/Hemosiderosis	High	Low	Low	High	High
Chronic Illness	Low	Low/Normal	Low/Normal	Low/Normal	Normal/High
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

Recent consumption of iron-rich foods or iron supplements can affect test results, as can recent blood transfusions.

Normal iron levels are maintained by a balance between the amount of iron taken into the body and the amount of iron lost. Normally, a small amount of iron is lost each day, so if too little iron is taken in, a deficiency will eventually develop. Unless a person has a poor diet, there is usually enough iron to prevent iron deficiency and/or iron deficiency anemia in healthy people.

In certain situations, there is an increased need for iron. Persons with chronic bleeding from the digestive tract (usually from ulcers or tumors such as colorectal cancer) or women with heavy menstrual periods will lose more iron than normal and can develop iron deficiency. Women who are pregnant or breast feeding lose iron to their baby and can develop iron deficiency if not enough extra iron is taken in. Children, especially during times of rapid growth, may need extra iron and can develop iron deficiency. Iron deficiency can also be seen in malabsorption diseases such as celiac disease.

Low serum iron can also occur in states where the body cannot mobilize and use storage iron properly. In many chronic inflammatory conditions, especially in cancers, autoimmune diseases, and with chronic inflammations or chronic infections (including AIDS), the body cannot properly use iron to make more red cells. Under these conditions, production of transferrin decreases, and serum iron is low because little iron is being absorbed from the gut and storage iron can’t get mobilized, and ferritin increases.

Iron deficiency

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 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 total iron-binding capacity (TIBC) and unsaturated iron-binding capacity (UIBC) increase. As this stage progresses, fewer and smaller red blood cells are produced, eventually resulting in iron deficiency anemia. Iron deficiency anemia refers to a drop in the number of red blood cells, hemoglobin and hematocrit caused by not having enough stored iron (there are many other causes of anemia). It typically takes several weeks after iron stores are depleted for the level of hemoglobin and production of red blood cells to be affected and for anemia to develop. There usually are few symptoms early in iron deficiency, but as the condition worsens and blood levels of hemoglobin and red blood cells decrease, then ongoing weakness and fatigue can eventually develop.

As your iron continues to be depleted, you may have shortness of breath and dizziness. If the anemia is severe, chest pain, headaches, and leg pains may occur. Children may develop learning (cognitive) disabilities. Besides the general symptoms of anemia, there are certain symptoms that are characteristic of iron deficiency. These include dysphagia, pica (cravings for specific substances, such as ice, corn starch, licorice, chalk, dirt, or clay), a burning sensation in the tongue or a smooth tongue, sores at the corners of the mouth, and spoon-shaped fingernails and toenails.

Decreases in the serum iron level are associated with the following ¹:

• Iron deficiency anemia
• Nephrotic syndrome(loss of iron-binding proteins)
• Iron deficiency
• Chronic renal failure
• Many infections
• Active hematopoiesis
• Remission of pernicious anemia
• Hypothyroidism
• Malignancy (carcinoma)
• Postoperative state
• Kwashiorkor

Iron overload

If the iron level is high, the total iron-binding capacity (TIBC), unsaturated iron-binding capacity (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 or over a short period of time. 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 people with alcoholism and with chronic liver disease also develop iron overload.

Increases in serum iron level are associated with the following ²:

• Idiopathic hemochromatosis
• Liver necrosis (viral hepatitis)
• Hemosiderosis caused by excessive iron intake (eg, multiple transfusions, excess iron administration)
• Acute iron poisoning (children)
• Hemolytic anemia
• Pernicious anemia
• Aplastic or hypoplastic anemia
• Lead poisoning
• Thalassemia
• Vitamin B6 deficiency
• Estrogens
• Ethanol
• Oral contraceptive

When is iron studies ordered?

Iron studies may be ordered 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.

Iron studies may be ordered when a person develops signs and symptoms of anemia, such as:

• Chronic fatigue/tiredness
• Dizziness
• Weakness
• Headaches
• Pale skin (pallor)

Iron studies 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
• Lack of energy
• Abdominal pain
• Loss of sex drive
• Organ damage, such as in the heart and/or liver

When a child is suspected to have ingested an excessive amount of iron tablets, a serum iron test is ordered to detect and help assess the severity of the poisoning.

References

1. Beutler E. Disorders of Iron Metabolism. Prchal JT KK, Lichtman MA, Kipps TJ, Seligsohn U, ed. Williams Hematology. 8th ed. New York: McGraw-Hill; 2010.
2. Williamson MA, Snyder LM, Wallach JB. Wallach’s interpretation of diagnostic tests. 9th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health; 2011.