Patient education: Anemia caused by low iron in adults (Beyond the Basics)

IRON DEFICIENCY ANEMIA OVERVIEW — Anemia can be caused by a number of different conditions, including heavy menstrual periods, pregnancy, cancer, and bleeding in the digestive tract, to name a few. Iron deficiency anemia is a type of anemia that occurs when there is not enough iron to make the hemoglobin in red blood cells. Hemoglobin is the protein in red blood cells that helps carry oxygen to the body's organs and tissues. The main causes of iron deficiency anemia in adults are bleeding and conditions that block iron absorption in the intestines.

Iron deficiency anemia can be mild or severe. The condition is common in the United States, especially in females who are still having menstrual periods or are or have been pregnant. It is less common in males. It is even more common in parts of the world where people cannot get sufficient iron from food and in regions where intestinal parasites are common, especially hookworm and tapeworm.

This topic will review the signs and symptoms, potential causes, diagnostic tests, and treatment of iron deficiency anemia in adults.

WHAT IS ANEMIA? — Anemia is defined as a decreased number of red blood cells (RBCs), as measured by one of the following blood tests:

●Hemoglobin (Hb) is the iron-containing molecule in RBCs that carries oxygen. Iron is a critical component of hemoglobin; without iron, hemoglobin cannot be formed and fewer RBCs are produced. This is the most accurate of the tests as it is measured on specialized machinery in a laboratory or in the doctor's office.

●Hematocrit (Hct) is the percent of a sample of blood made up of RBCs. The rest of the blood is mostly made up of a fluid called plasma. This test used to be more popular, but the hemoglobin is considered more reliable because hemoglobin is measured and hematocrit is calculated.

●RBC count is the number of RBCs in a certain amount of whole blood, usually one microliter (one millionth of a liter).

Iron deficiency (too little iron) anemia occurs when there is insufficient iron in the body to make hemoglobin. When the quantity of hemoglobin is reduced, fewer RBCs are formed, and the RBCs that are formed are smaller. Symptoms of iron deficiency vary from person to person. Iron deficiency can even cause symptoms in the absence of anemia. Over time, without iron, anemia will develop.

ANEMIA SIGNS AND SYMPTOMS — Many people with iron deficiency anemia have no symptoms at all. Of those who do, the most common symptoms include:

●Weakness

●Headache

●Irritability

●Fatigue

●Difficulty exercising (due to shortness of breath or exhaustion)

●Brittle nails

●Sore tongue

●Restless legs syndrome

●Pica (an abnormal craving to eat nonfood items, such as clay or dirt, paper products, or cornstarch)

●Pagophagia (a form of pica in which there is an abnormal craving to eat ice)

CAUSES OF ANEMIA — Common causes of iron deficiency anemia are blood loss (most common) and decreased absorption of iron from food.

Blood loss — The source of blood loss may be obvious, such as in people who have heavy menstrual bleeding or a person with a known bleeding ulcer. Pregnancy can use up as much as five- to six-fold more iron for the developing fetus and placenta (figure 1). Blood loss during childbirth can also contribute to iron deficiency.

In other cases, the source of the blood loss is not visible, as in someone who has chronic bleeding in their gastrointestinal (GI) tract (stomach, small intestine, colon). This may appear as diarrhea with black, tarry stools, or, if the blood loss is very slow, the stool may appear normal. Donating blood can also cause iron deficiency, especially if it is done on a regular basis. Anyone with unexplained iron deficiency should get a thorough evaluation to make sure a serious cause is not missed, like cancer of the GI tract.

Decreased iron absorption — Normally, the body absorbs iron from food through the GI tract. In people with certain conditions such as celiac disease, autoimmune gastritis, Helicobacter pylori (H. pylori) infection, other forms of stomach inflammation, gastric bypass surgery (for weight loss), or other forms of weight loss surgery, an inadequate amount of iron may be absorbed, leading to iron deficiency anemia.

Other causes — In some parts of the world, there is not enough iron available from food, and iron deficiency may develop due to low iron intake. In some countries such as the United States, some foods have added iron (breakfast cereal, bread, pasta). Iron is also available in some plant-based foods. (See 'Iron and diet' below.)

ANEMIA DIAGNOSIS — Since iron deficiency occurs before anemia develops, a person may be diagnosed with iron deficiency with or without anemia. In some cases, testing is done to evaluate symptoms, and in others it is done for an unrelated reason.

The initial evaluation generally involves a medical history to look for possible causes of iron deficiency; physical examination to look for causes and typical findings of iron deficiency; and blood tests to measure iron stores in the body and check for other possible conditions that could contribute to iron deficiency. This is especially important in early pregnancy, where the likelihood of having iron deficiency is as high as 40 percent in high-resource countries and up to 90 percent in resource-limited countries.

Complete blood count — A complete blood count (CBC) is a group of tests that includes a red blood cell (RBC) count, hemoglobin (Hb), and hematocrit (Hct). It reports the size of the RBCs (referred to as the mean corpuscular volume), amount of hemoglobin per RBC (referred to as mean corpuscular hemoglobin [MCH]), and others. It also measures white blood cells and platelets, which are the two other main types of blood cells.

In people with iron deficiency anemia, the RBC count, Hb, and Hct can be low. The MCV and MCH are usually normal early on but can become lower over time, indicating that the RBCs are smaller (called microcytic) and contain less Hb than normal RBCs.

The shape, color, and size of the RBCs can help to determine the type of anemia.

White blood cells are not affected by iron deficiency. Platelets may be increased in some cases, or they may be normal.

Other blood tests — In many cases, iron deficiency anemia is suspected based upon the results of the medical history and the CBC. Further testing is used to confirm the diagnosis.

Blood tests to check iron levels include:

●Ferritin — Measures a protein that stores iron. This protein decreases when a person has iron deficiency. The ferritin measurement is most useful when it is low, as nothing other than iron deficiency causes a low ferritin. In some cases, the ferritin level can be checked by itself. In others, an "iron studies panel" is used that contains the other tests listed below.

Ferritin can increase in some conditions unrelated to iron, which can confuse the interpretation of the results. These are generally conditions associated with inflammation, such as chronic rheumatologic disorders (inflammation of the joints) or infections. In people with chronic inflammation, the transferrin saturation (TSAT; see below) and sometimes other specialized testing can be used to see if there is a need for iron replacement.

●Serum iron — Measures how much iron is circulating in the blood. The result can be affected by iron supplements and even recent meals. It is not a good measure of the iron stores in the body.

●Total iron binding capacity (TIBC or transferrin) — Measures the amount of a protein (transferrin) in the blood that transports iron to RBCs or storage cells. When iron stores are low, the TIBC or transferrin increases.

●Transferrin saturation (TSAT) — Measures how much iron is bound to transferrin. This number is a percentage, calculated by dividing the serum iron by the TIBC. A lower TSAT indicates iron deficiency. If this test is being used to make the diagnosis, it may be done on an overnight fast (after not eating for a night) because iron in foods can sometimes make the TSAT appear higher than it should be.

In a person with iron deficiency anemia the ferritin and the TSAT are the most useful tests. In iron deficiency, the ferritin and TSAT are low.

Search for source of blood and iron loss — Once the diagnosis of iron deficiency anemia is made, it is very important to identify the cause. Your health care team may ask questions about the following causes:

●History of heavy menstrual periods, pregnancies, and deliveries

●Gastrointestinal (GI) problems such as ulcers, Helicobacter pylori (H. pylori) infection, autoimmune gastritis, or celiac disease

●Signs of bleeding from the GI tract such as dark, tarry stools (even if only occasionally), visible bleeding, or vomiting dark-colored material

●Travel history (if the person has visited a place where GI parasites are common)

●Surgery on the GI tract (such as gastric bypass for weight loss)

●Family or personal history of bleeding disorders

●Family or personal history of colon cancer

●Multiple blood donations

●Use of medications that can irritate the GI tract, such as nonsteroidal antiinflammatory drugs (NSAIDs), which include aspirin, ibuprofen (sample brand names: Advil, Motrin) and naproxen (sample brand names: Aleve, Naprosyn)

If a cause of blood loss is not obvious (or if a GI source of blood loss is suspected), additional tests should be done. These include colonoscopy or upper endoscopy to look for areas of bleeding in the GI tract, and blood tests for certain conditions that interfere with iron absorption, such as autoimmune gastritis, celiac disease, and H. pylori infection. Looking for bleeding in the colon is especially important in people over the age of 40 to 50. (See "Patient education: Colonoscopy (Beyond the Basics)" and "Patient education: Upper endoscopy (Beyond the Basics)" and "Patient education: Helicobacter pylori infection and treatment (Beyond the Basics)".)

TREATMENT

Iron administration — Iron deficiency is treated with iron supplements, which can be given orally (as a pill) or intravenously (this is sometimes called "parenteral iron" or "IV iron"). Iron allows the body to increase production of hemoglobin (Hb) and rebuild the body's iron reserves. In rare cases of severe anemia, a blood transfusion is needed.

The choice between oral and IV iron depends on several factors, including the severity of anemia, the cause of iron deficiency, and whether oral iron is well-tolerated. In general:

●Oral iron tablets are used in most people with iron deficiency anemia and iron deficiency without anemia.

●Intravenous iron can be used for people whose GI tract cannot adequately absorb iron (such as gastric bypass surgery), during the second and third trimester of pregnancy, or, more commonly, in those who are unable to tolerate oral iron. Some people experience side effects like constipation, nausea, or cramping, which can make the supplements hard to take. Intravenous iron is often given to people with chronic kidney disease and people with inflammatory bowel disease. During pregnancy, the developing fetus needs iron for normal brain development, and iron deficiency is associated with a number of problems for both mother and child.

●A blood transfusion may be given if a person is actively bleeding and/or the Hb or hematocrit (Hct) levels are very low, but transfusions are not commonly needed.

All of these treatment approaches are discussed more below.

Find and treat the cause — It is also critically important to determine the cause of iron deficiency and correct it, so that iron does not continue to be lost, and any serious condition (for example, colon cancer) is treated as early as possible.

Oral iron — Oral iron tablets are a safe, inexpensive, and effective treatment for people with iron deficiency. Gastrointestinal (GI) side effects are common and should be discussed with your doctor; these are discussed below. (See 'Side effects' below.)

The following tips are recommended when taking oral iron:

●Iron is best absorbed if it is taken every other day (or, for example, on Monday, Wednesday, and Friday), for people who are able to keep track of this type of schedule.

●Certain foods and medicines can reduce the absorption of iron tablets. Iron tablets usually should not be taken with tea, coffee, calcium supplements, or milk. Iron can be taken one hour before or two hours after these items. If you take antacids, your iron tablets should be taken at least two hours before or four hours after the antacids. Tell your doctor if you take any supplements, vitamins, or other medications.

●"Enteric coated" (EC) iron tablets should be avoided. These tablets have a special coating that does not dissolve quickly in the GI tract. These are not recommended because iron is best absorbed from the duodenum and jejunum (the first and middle parts of the small intestine), and EC iron releases iron further down in the intestinal tract, where it is not as easily absorbed. In some cases, an EC iron tablet can pass through the entire intestinal tract with the coating intact, meaning that none of the iron was absorbed.

Types of oral iron — There are several forms of oral iron, and with the exception of the enteric coated (EC) iron tablets mentioned above, they are all equally effective. Different formulations contain different amounts of iron. For many products, the number of milligrams for the pill is different from the number of milligrams of actual iron molecules (called "elemental iron"):

●Ferrous fumarate — 106 mg elemental iron/tablet

●Ferrous sulfate — 65 mg elemental iron/tablet

●Ferrous sulfate liquid — 44 mg elemental iron/teaspoon (5 mL)

●Ferrous gluconate — 28 to 36 mg iron/tablet

●Polysaccharide-iron complex – various doses available

In the past, iron pills were typically prescribed once or multiple times per day. Recent evidence suggests that taking oral iron every other day (or on Monday, Wednesday, and Friday) allows the body to absorb more iron, while reducing GI side effects. (See 'Side effects' below.)

Side effects — Some people experience a metallic taste, nausea, constipation, stomach upset, nausea, vomiting, and/or dark-colored stools after taking oral iron. Options for dealing with these side effects include:

●Take a smaller dose

●Take iron with food (even though this will reduce the amount of iron your body absorbs, it's better than not taking it at all)

●Use a formulation with a lower elemental iron content (eg, ferrous gluconate instead of ferrous sulfate)

●Take the liquid form of ferrous sulfate and adjust the dose until symptoms are tolerable

●Switch to IV iron

Taking iron tablets can turn the stool a dark, almost black color (actually dark green). This is normal, and does not mean that the iron tablets are causing GI bleeding.

Children are at particular risk of iron poisoning (overdose), making it very important to store iron tablets out of the reach of children. If you think a child ingested iron pills, call a poison control center (in the United States, 1-800-222-1222) or their pediatrician.

Duration of treatment — Treatment with oral iron is recommended for as long as it takes the hemoglobin (Hb) and hematocrit (Hct), and usually the tests of iron stores, to return to normal. Typically this takes approximately six months with oral iron. Treatment with IV iron is completed with one or more doses. (See 'Intravenous iron' below.)

If oral iron does not increase hemoglobin — On occasion, a person's Hb will not improve despite treatment with oral iron. There are several possible reasons for this. The next step depends upon why the person's Hb did not increase, which needs to be evaluated by a clinician. However, several points are worth keeping in mind:

●It is important that iron be taken. Not taking iron as prescribed is probably the most common reason it does not work. If side effects are preventing you from taking oral iron, IV iron can be used instead.

●The type of iron preparation being taken is important. One should avoid any preparation that is labeled "slow release," or is enteric coated (EC), as these may prevent iron from being efficiently absorbed.

●Another condition may prevent iron from being absorbed, such as autoimmune gastritis, celiac disease, or Helicobacter pylori infection. These conditions can be diagnosed by blood tests in some cases.

●In some people, there may be another cause of anemia in addition to iron deficiency, such as vitamin B12 deficiency. In others, the diagnosis of iron deficiency may be incorrect.

●If there is ongoing bleeding that depletes iron stores faster than they are being replaced, it may appear that the oral iron is not working.

●During the second and third trimester of pregnancy, oral iron may take too long to correct iron deficiency in time to provide iron to the developing fetus.

●For any of the above, changing to IV iron may be a good option.

Intravenous iron

Uses — Iron may be given by IV injection in certain situations, such as in people who cannot tolerate the side effects of oral iron or whose GI tract cannot absorb an adequate amount of iron from pills.

People who may be candidates for IV iron due to health conditions include those who:

●Have inflammatory bowel disease

●Have chronic kidney disease

●Have had bariatric (weight loss) surgery

●Are pregnant, especially in the late second and third trimesters

IV iron is infused into a vein. This is done in a doctor's office or hospital, where the person can be monitored. The length of time required for the infusion and the number of infusions needed depend on which iron product is used and the severity of iron deficiency.

Side effects — The IV iron used in the past (high molecular weight iron dextran [brand name: Dexferrum]) had a risk of severe allergic reactions. However, IV iron products used today have an exceedingly low risk of allergic or anaphylactic reactions (less than one tenth of one percent). Infusion reactions are more common, and may include temporary flushing, back pain, and other symptoms that usually go away when the infusion is slowed or stopped. Some patients with a history of rheumatoid arthritis may have an arthritis flare, which can be reduced or prevented by a short course of steroids.

The best ways to minimize these reactions include avoiding the use of antihistamines as "premedication" or to treat minor symptoms, giving the infusion more slowly, or in some people (those with a history of multiple drug allergies) giving a steroid before the infusion.

If you have back pain or joint pain at home after the infusion, a nonsteroidal antiinflammatory drug (NSAID) may be helpful. NSAIDs include ibuprofen (sample brand names: Advil, Motrin) and naproxen (sample brand name: Aleve).

Blood transfusion

Uses — Blood transfusion may be used in people with anemia that is severe or causes significant symptoms such as chest pain or difficulty breathing.

Blood transfusion involves giving one or more units of packed red blood cells (pRBCs) into a vein. Each unit of pRBCs contains the RBCs from one unit of blood donated by a voluntary donor. It contains approximately 200 mg of iron and will raise the hemoglobin (Hb) by approximately 1 gram/deciliter (g/dL; 1 gram per 100 milliliters).

Blood transfusions are generally reserved for people who have a very low Hb level (less than 7 g/dL), low or unstable blood pressure, and/or breathing difficulties caused by severe anemia. Symptoms may include chest pain and/or shortness of breath, or in more extreme circumstances, passing out.

Blood transfusion is described in detail in a separate topic. (See "Patient education: Blood donation and transfusion (Beyond the Basics)".)

Side effects — There can be side effects of blood transfusion, with the most common being fever or itching. However, this only occurs in 0.1 to 1 percent of transfusions. More serious or even life-threatening allergic reactions or other complications can occur, although this is even less common.

The risk of infection with the hepatitis C virus or the HIV virus is extremely low because of better screening of blood donors as well as improved laboratory testing. These infections occur approximately once in every two million transfusions (table 1).

Iron and diet — Although dietary iron is important in preventing iron deficiency, people with iron deficiency anemia need more iron than they can consume through their diet alone. A 2000 calorie diet contains approximately 10 mg of elemental iron (compared with 65 mg in one 325 mg ferrous sulfate tablet). Therefore, increasing dietary iron alone is not usually sufficient as a treatment for iron deficiency anemia.

Dietary sources of iron include meat, especially organ meats, grains, fruits, and vegetables (table 2). For people who do not eat meat, good plant sources of iron include whole or enriched breads or grains, iron-fortified cereals, legumes (beans, chickpeas, peanuts), green leafy vegetables, dried fruits, soy products, blackstrap molasses, bulgur, and wheat germ. Maintaining a healthy, balanced diet is good for your overall health.

PREVENTION — Some people will require iron supplementation for life. For example, people who have had weight loss surgery may continue to need iron supplements to maintain the body's iron stores.

Extra iron is commonly included in prenatal multivitamins to prevent iron deficiency from developing during pregnancy, but it may not be sufficient to treat iron deficiency. Iron deficiency is very common in pregnancy.

Iron supplements and multivitamins that contain iron should not be taken without consulting your health care team, because too much iron in the body can also cause problems.

Most people do not need supplemental iron unless they have an underlying illness that reduces iron absorption or causes bleeding.

COMMUNICATING WITH YOUR HEALTH CARE TEAM — It is essential to communicate openly with your health care team and be thorough and honest about your health history. Your health history includes any recent surgeries, medications, blood donations, and dietary and exercise habits. All of this information can help your team to diagnose and treat your iron deficiency anemia.

Your opinion matters when creating your care plan. If you do not understand your diagnosis or treatment plan, or if you any have questions, concerns, or side effects of treatment, let your team know. They can help.

WHERE TO GET MORE INFORMATION — Your health care team is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Complete blood count (CBC) (The Basics)
Patient education: Anemia caused by low iron (The Basics)
Patient education: Nutrition before and during pregnancy (The Basics)
Patient education: Restless legs syndrome (The Basics)
Patient education: Angiodysplasia of the GI tract (The Basics)
Patient education: Medicines for chronic kidney disease (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Screening for colorectal cancer (Beyond the Basics)
Patient education: Blood donation and transfusion (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Diagnostic approach to anemia in adults
Iron requirements and iron deficiency in adolescents
Causes and diagnosis of iron deficiency and iron deficiency anemia in adults
Treatment of iron deficiency anemia in adults
Indications and hemoglobin thresholds for red blood cell transfusion in the adult

The following websites also provide reliable health information.

●National Library of Medicine

     (https://medlineplus.gov/ency/article/000584.htm)

●National Institutes of Health (NIH)

     (https://ods.od.nih.gov/factsheets/Iron-Consumer/)

●National Heart, Lung, and Blood Institute

     (www.nhlbi.nih.gov/health/dci/Diseases/ida/ida_diagnosis.html)

●Centers for Disease Control and Prevention

(https://www.cdc.gov/nutrition/infantandtoddlernutrition/vitamins-minerals/iron.html)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges the extensive contributions of William C Mentzer, MD, to earlier versions of this and many other topic reviews.