What is microcytic anemia

Microcytic anemia (anemia due to smaller than normal red blood cells) may be due to low iron levels, lead poisoning, or thalassemia.

Iron deficiency anemia and β-thalassemia are the most common causes of microcytic anemia ¹⁾.

Definitive methods for diagnosis of thalassemia trait include quantitative analysis of HbA₂ and DNA studies for specific deletions and mutations. Increased HbA₂ is considered to be confirmatory for β-thalassemia trait. Low or normal values and no evidence of iron deficiency suggest α-thalassemia; definitive diagnosis requires molecular methods to detect gene deletions.

What is thalassemia

Thalassemia is an inherited genetic blood disorder in which part of the hemoglobin is abnormal. People with thalassaemia do not produce enough healthy hemoglobin. Hemoglobin is an iron-rich protein found in red blood cells that carries oxygen from the lungs to the rest of the body. Hemoglobin is an iron-rich protein in red blood cells. Hemoglobin also carries carbon dioxide (a waste gas) from the body to the lungs, where it’s exhaled.

Thalassemia is characterized by less hemoglobin and fewer red blood cells in your body than normal. The low hemoglobin and fewer red blood cells of thalassemia may cause anemia, leaving you fatigued.

Normal hemoglobin, also called hemoglobin A (Hb A), has four protein chains—two alpha globin and two beta globin (see Figure 1).

Normal haemoglobin types include ²⁾:

• Hb A – makes up about 95%-98% of hemoglobin found in adults); contains two alpha (α) protein chains and two beta (β) protein chains
• Hb A2 – makes up about 2%-3% of hemoglobin; has two alpha (α) and two delta (δ) protein chains
• Hb F – makes up to 2% of hemoglobin found in adults; has two alpha (α) and two gamma (γ) protein chains; the primary haemoglobin produced by the foetus during pregnancy; its production usually falls to a low level shortly after birth

There are two main types, alpha thalassemia (α thalassemia) and beta thalassemia (β thalassemia) ³⁾. The two major types of thalassemia, alpha and beta, are named after defects in these protein chains. The severity of alpha and beta thalassemia depends on how many of the four genes for alpha globin or two genes for beta globin are missing.

Four genes (two from each parent) are needed to make enough alpha globin protein chains. Alpha thalassemia (α thalassemia) trait occurs if one or two of the four genes are missing. If more than two genes are missing, moderate to severe anemia occurs.

Thalassemia can be mild (often called thalassaemia minor) or it can be severe. Thalassemia which causes serious problems can be called thalassemia major, Cooley’s anemia or Mediterranean anemia, depending on the genetic defect.

The most severe form of alpha thalassemia (α thalassemia) is called alpha thalassemia major or hydrops fetalis. Babies who have this disorder usually die before or shortly after birth.

Two genes (one from each parent) are needed to make enough beta globin protein chains. Beta thalassemia (β thalassemia) occurs if one or both genes are altered.

The severity of beta thalassemia (β thalassemia) depends on how much one or both genes are affected. If both genes are affected, the result is moderate to severe anemia. The severe form of beta thalassemia is known as thalassemia major or Cooley’s anemia.

Thalassemias affect males and females equally. The disorders occur most often among people of Italian, Greek, Middle Eastern, Southeast and Central Asian, and North African descent. Severe forms usually are diagnosed in early childhood and are lifelong conditions.

As of 2013, thalassemia occurs in about 280 million people, with about 439,000 having severe disease ⁴⁾.

Doctors diagnose thalassemias using blood tests including a complete blood count, special hemoglobin tests, and genetic tests. Diagnosis may occur before birth through prenatal testing. The disorders are treated with blood transfusions, medicines, and other procedures.

Thalassemias other names

The various types of thalassemia have specific names related to the severity of the disorder.

Alpha Thalassemias (α Thalassemias)

• Alpha thalassemia silent carrier
• Alpha thalassemia minor, also called alpha thalassemia trait
• Hemoglobin H disease
• Alpha thalassemia major, also called hydrops fetalis

Beta Thalassemias (β Thalassemia)

• Beta thalassemia minor, also called beta thalassemia trait
• Beta thalassemia intermedia
• Beta thalassemia major, also called Cooley’s anemia or beta-zero (ß0) thalassemia
• Beta-plus (ß+) thalassemia
• Mediterranean anemia

Outlook (Prognosis) of Thalassemias

Treatments for thalassemias have improved over the years. People who have moderate or severe thalassemias are now living longer and have better quality of life.

However, complications from thalassemias and their treatments are frequent. People who have moderate or severe thalassemias must closely follow their treatment plans. They need to take care of themselves to remain as healthy as possible.

Complications of Thalassemias

Better treatments now allow people who have moderate and severe thalassemias to live much longer. As a result, these people must cope with complications of these disorders that occur over time.

Heart and Liver Diseases

Regular blood transfusions are a standard treatment for thalassemias. Transfusions can cause iron to build up in the blood (iron overload). This can damage organs and tissues, especially the heart and liver.

Heart disease caused by iron overload is the main cause of death in people who have thalassemias. Heart disease includes heart failure, arrhythmias (irregular heartbeats), and heart attack.

Infection

Among people who have thalassemias, infections are a key cause of illness and the second most common cause of death. People who have had their spleens removed are at even higher risk because they no longer have this infection-fighting organ.

Osteoporosis

Many people who have thalassemias have bone problems, including osteoporosis. This is a condition in which bones are weak and brittle and break easily.

Figure 1. Red blood cell hemoglobin (normal hemoglobin)

Causes of thalassemias

Your body makes three types of blood cells: red blood cells, white blood cells, and platelets. Red blood cells contain hemoglobin, an iron-rich protein that carries oxygen from your lungs to all parts of your body. Hemoglobin also carries carbon dioxide (a waste gas) from your body to your lungs, where it’s exhaled.

Hemoglobin has two kinds of protein chains: alpha globin and beta globin. If your body doesn’t make enough of these protein chains or they’re abnormal, red blood cells won’t form correctly or carry enough oxygen. Your body won’t work well if your red blood cells don’t make enough healthy hemoglobin.

Genes control how the body makes hemoglobin protein chains. When these genes are missing or altered, thalassemias occur.

Thalassemias are inherited disorders—that is, they’re passed from parents to children through genes. People who inherit faulty hemoglobin genes from one parent but normal genes from the other are called carriers. Carriers often have no signs of illness other than mild anemia. However, they can pass the faulty genes on to their children.

People who have moderate to severe forms of thalassemia have inherited faulty genes from both parents (see Figure 2).

Figure 2. Thalassemia inheritance pattern

Alpha Thalassemias

You need four genes (two from each parent) to make enough alpha globin protein chains. If one or more of the genes is missing, you’ll have alpha thalassemia trait or disease. This means that your body doesn’t make enough alpha globin protein (see Figure 3).

If you’re only missing one gene, you’re a “silent” carrier. This means you won’t have any signs of illness.
If you’re missing two genes, you have alpha thalassemia trait (also called alpha thalassemia minor). You may have mild anemia.
If you’re missing three genes, you likely have hemoglobin H disease (which a blood test can detect). This form of thalassemia causes moderate to severe anemia.

Very rarely, a baby is missing all four genes. This condition is called alpha thalassemia major or hydrops fetalis. Babies who have hydrops fetalis usually die before or shortly after birth.

Figure 3. Inheritance Pattern for Alpha Thalassemia

Note: The picture shows one example of how alpha thalassemia is inherited. The alpha globin genes are located on chromosome 16. A child inherits four alpha globin genes (two from each parent). In this example, the father is missing two alpha globin genes and the mother is missing one alpha globin gene. Each child has a 25 percent chance of inheriting two missing genes and two normal genes (thalassemia trait), three missing genes and one normal gene (hemoglobin H disease), four normal genes (no anemia), or one missing gene and three normal genes (silent carrier).

Beta Thalassemias

You need two genes (one from each parent) to make enough beta globin protein chains. If one or both of these genes are altered, you’ll have beta thalassemia. This means that your body won’t make enough beta globin protein.

• If you have one altered gene, you’re a carrier. This condition is called beta thalassemia trait or beta thalassemia minor. It causes mild anemia.
• If both genes are altered, you’ll have beta thalassemia intermedia or beta thalassemia major (also called Cooley’s anemia). The intermedia form of the disorder causes moderate anemia. The major form causes severe anemia.

Figure 4. Inheritance Pattern for Beta Thalassemia

Note: The picture shows one example of how beta thalassemia is inherited. The beta globin gene is located on chromosome 11. A child inherits two beta globin genes (one from each parent). In this example, each parent has one altered beta globin gene. Each child has a 25 percent chance of inheriting two normal genes (no anemia), a 50 percent chance of inheriting one altered gene and one normal gene (beta thalassemia trait), or a 25 percent chance of inheriting two altered genes (beta thalassemia major).

Risk Factors for thalassemias

Family history and ancestry are the two risk factors for thalassemias.

Family History

Thalassemias are inherited—that is, the genes for the disorders are passed from parents to their children. If your parents have missing or altered hemoglobin-making genes, you may have thalassemia.

Ancestry

Thalassemias occur most often among people of Italian, Greek, Middle Eastern, Southern Asian, and African descent.

Screening and Prevention for thalassemias

You can’t prevent thalassemias because they’re inherited (passed from parents to children through genes). However, prenatal tests can detect these blood disorders before birth.

Family genetic studies may help find out whether people have missing or altered hemoglobin genes that cause thalassemias.

If you know of family members who have thalassemias and you’re thinking of having children, consider talking with your doctor and a genetic counselor. They can help determine your risk for passing the disorder to your children.

Thalassemia signs and symptoms

A lack of oxygen in the bloodstream causes the signs and symptoms of thalassemias. The lack of oxygen occurs because the body doesn’t make enough healthy red blood cells and hemoglobin. The severity of symptoms depends on the severity of the disorder.

People with thalassemia can:

• feel tired, weak and short of breath
• grow more slowly than usual as children
• be pale or have yellow skin coloring (jaundice)
• have dark urine
• have a swollen belly
• have slight deformity of their facial bones.

The symptoms can show up in babies and small children if the condition is severe.

No Symptoms

Alpha thalassemia silent carriers generally have no signs or symptoms of the disorder. The lack of alpha globin protein is so minor that the body’s hemoglobin works normally.

Mild Anemia

People who have alpha or beta thalassemia trait can have mild anemia. However, many people who have these types of thalassemia have no signs or symptoms.

Mild anemia can make you feel tired. Mild anemia caused by alpha thalassemia trait might be mistaken for iron-deficiency anemia.

Mild to Moderate Anemia and Other Signs and Symptoms

People who have beta thalassemia intermedia have mild to moderate anemia. They also may have other health problems, such as:

• Slowed growth and delayed puberty. Anemia can slow down a child’s growth and development.
• Bone problems. Thalassemia may cause bone marrow to expand. Bone marrow is the spongy substance inside bones that makes blood cells. When bone marrow expands, the bones become wider than normal. They may become brittle and break easily.
• An enlarged spleen. The spleen is an organ that helps your body fight infection and remove unwanted material. When a person has thalassemia, the spleen has to work very hard. As a result, the spleen becomes larger than normal. This makes anemia worse. If the spleen becomes too large, it must be removed.

Severe Anemia and Other Signs and Symptoms

People who have hemoglobin H disease or beta thalassemia major (also called Cooley’s anemia) have severe thalassemia. Signs and symptoms usually occur within the first 2 years of life. They may include severe anemia and other health problems, such as:

• A pale and listless appearance
• Poor appetite
• Dark urine (a sign that red blood cells are breaking down)
• Slowed growth and delayed puberty
• Jaundice (a yellowish color of the skin or whites of the eyes)
• An enlarged spleen, liver, or heart
• Bone problems (especially with bones in the face)

Thalassemia diagnosis

Some people find out they have Thalassemia because they are unwell. Their doctor talks to them, examines them and carries out blood tests. They may also have genetic tests.

Other people find out they have Thalassemia by chance, when a blood test done for other reasons shows something unusual.

There are times when doctors suggest a blood test to check for Thalassemia. This includes if:

• you are planning to have a child
• you have a relative with Thalassemia
• you or your relatives have unexplained anemia (low iron)
• your family came from a region where Thalassemia is common.

Unborn babies can also be tested for Thalassemia.

Doctors diagnose thalassemias using blood tests, including a complete blood count (CBC) and special hemoglobin tests.

• A complete blood count (CBC) measures the amount of hemoglobin and the different kinds of blood cells, such as red blood cells, in a sample of blood. People who have thalassemias have fewer healthy red blood cells and less hemoglobin than normal in their blood. People who have alpha or beta thalassemia trait may have red blood cells that are smaller than normal.
• Hemoglobin tests measure the types of hemoglobin in a blood sample. People who have thalassemias have problems with the alpha or beta globin protein chains of hemoglobin.

Moderate and severe thalassemias usually are diagnosed in early childhood. This is because signs and symptoms, including severe anemia, often occur within the first 2 years of life.

People who have milder forms of thalassemia might be diagnosed after a routine blood test shows they have anemia. Doctors might suspect thalassemia if a person has anemia and is a member of an ethnic group that’s at increased risk for thalassemias.

Doctors also test the amount of iron in the blood to find out whether the anemia is due to iron deficiency or thalassemia. Iron-deficiency anemia occurs if the body doesn’t have enough iron to make hemoglobin. The anemia in thalassemia occurs because of a problem with either the alpha globin or beta globin chains of hemoglobin, not because of a lack of iron.

Because thalassemias are passed from parents to children through genes, family genetic studies also can help diagnose the disorder. These studies involve taking a family medical history and doing blood tests on family members. The tests will show whether any family members have missing or altered hemoglobin genes.

If you know of family members who have thalassemias and you’re thinking of having children, consider talking with your doctor and a genetic counselor. They can help determine your risk for passing the disorder to your children.

If you’re expecting a baby and you and your partner are thalassemia carriers, you may want to consider prenatal testing.

Prenatal testing involves taking a sample of amniotic fluid or tissue from the placenta. Amniotic fluid is the fluid in the sac surrounding a growing embryo. The placenta is the organ that attaches the umbilical cord to the mother’s womb. Tests done on the fluid or tissue can show whether your baby has thalassemia and how severe it might be.

Thalassemia treatment

If you have Thalassemia, treatments for thalassemias depend on the type and severity of the disorder. It depends on how severe your symptoms are.

People who are carriers or who have alpha or beta thalassemia trait have mild or no symptoms. They’ll likely need little or no treatment.

People with severe Thalassemia may need blood transfusions every three to four weeks. People with less severe Thalassemia might need blood transfusions only occasionally, or not at all.

Blood transfusions can cause a build-up of iron in the body, which can lead to heart and liver damage. People with frequent blood transfusions can take a medicine that helps bring the iron back to a safe level.

A few people have so serious a problem that they are advised to have a transplantation of stem cells or bone marrow from a healthy donor. This can help, but it has risks and is only rarely needed.

If you carry the Thalassemia gene and are thinking of having a child, you may decide to have genetic testing. Your child is only at risk of having Thalassemia if both you and your partner are carriers.

Standard Treatments

Doctors use three standard treatments for moderate and severe forms of thalassemia. These treatments include blood transfusions, iron chelation therapy, and folic acid supplements. Other treatments have been developed or are being tested, but they’re used much less often.

Blood Transfusions

Transfusions of red blood cells are the main treatment for people who have moderate or severe thalassemias. This treatment gives you healthy red blood cells with normal hemoglobin.

During a blood transfusion, a needle is used to insert an intravenous (IV) line into one of your blood vessels. Through this line, you receive healthy blood. The procedure usually takes 1 to 4 hours.

Red blood cells live only for about 120 days. So, you may need repeated transfusions to maintain a healthy supply of red blood cells.

If you have hemoglobin H disease or beta thalassemia intermedia, you may need blood transfusions on occasion. For example, you may have transfusions when you have an infection or other illness, or when your anemia is severe enough to cause tiredness.

If you have beta thalassemia major (Cooley’s anemia), you’ll likely need regular blood transfusions (often every 2 to 4 weeks). These transfusions will help you maintain normal hemoglobin and red blood cell levels.

Blood transfusions allow you to feel better, enjoy normal activities, and live into adulthood. This treatment is lifesaving, but it’s expensive and carries a risk of transmitting infections and viruses (for example, hepatitis). However, the risk is very low in the United States because of careful blood screening.

Iron Chelation Therapy

The hemoglobin in red blood cells is an iron-rich protein. Thus, regular blood transfusions can lead to a buildup of iron in the blood. This condition is called iron overload. It damages the liver, heart, and other parts of the body.

To prevent this damage, doctors use iron chelation therapy to remove excess iron from the body. Two medicines are used for iron chelation therapy.

• Deferoxamine is a liquid medicine that’s given slowly under the skin, usually with a small portable pump used overnight. This therapy takes time and can be mildly painful. Side effects include problems with vision and hearing.
• Deferasirox is a pill taken once daily. Side effects include headache, nausea (feeling sick to the stomach), vomiting, diarrhea, joint pain, and tiredness.

Folic Acid Supplements

Folic acid is a B vitamin that helps build healthy red blood cells. Your doctor may recommend folic acid supplements in addition to treatment with blood transfusions and/or iron chelation therapy.

Other Treatments

Other treatments for thalassemias have been developed or are being tested, but they’re used much less often.

Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant replaces faulty stem cells with healthy ones from another person (a donor). Stem cells are the cells inside bone marrow that make red blood cells and other types of blood cells.

A stem cell transplant is the only treatment that can cure thalassemia. But only a small number of people who have severe thalassemias are able to find a good donor match and have the risky procedure.

Possible Future Treatments

Researchers are working to find new treatments for thalassemias. For example, it might be possible someday to insert a normal hemoglobin gene into stem cells in bone marrow. This will allow people who have thalassemias to make their own healthy red blood cells and hemoglobin.

Researchers also are studying ways to trigger a person’s ability to make fetal hemoglobin after birth. This type of hemoglobin is found in fetuses and newborns. After birth, the body switches to making adult hemoglobin. Making more fetal hemoglobin might make up for the lack of healthy adult hemoglobin.

Treating Complications

Better treatments now allow people who have moderate and severe thalassemias to live longer. As a result, these people must cope with complications that occur over time.

An important part of managing thalassemias is treating complications. Treatment might be needed for heart or liver diseases, infections, osteoporosis, and other health problems.

Living with Thalassemias

Survival and quality of life have improved for people who have moderate or severe thalassemias. This is because:

• More people are able to get blood transfusions now.
• Blood screening has reduced the number of infections from blood transfusions. Also, treatments for other kinds of infections have improved.
• Iron chelation treatments are available that are easier for some people to take.
• Some people have been cured through blood and marrow stem cell transplants.

Living with thalassemia can be challenging, but several approaches can help you cope.

Follow Your Treatment Plan

Following the treatment plan your doctor gives you is important. For example, get blood transfusions as your doctor recommends, and take your iron chelation medicine as prescribed.

Iron chelation treatment can take time and be mildly painful. However, don’t stop taking your medicine. The leading cause of death among people who have thalassemias is heart disease caused by iron overload. Iron buildup can damage your heart, liver, and other organs.

Several chelation treatments are now available, including injections and pills. Your doctor will talk with you about which treatment is best for you.

Take folic acid supplements if your doctor prescribes them. Folic acid is a B vitamin that helps build healthy red blood cells. Also, talk with your doctor about whether you need other vitamin or mineral supplements, such as vitamins A, C, or D or selenium.

Get Ongoing Medical Care

Keep your scheduled medical appointments, and get any tests that your doctor recommends.

These tests may include:

• Monthly complete blood counts and tests for blood iron levels every 3 months
• Yearly tests for heart function, liver function, and viral infections (for example, hepatitis B and C and HIV)
• Yearly tests to check for iron buildup in your liver
• Yearly vision and hearing tests
• Regular checkups to make sure blood transfusions are working
• Other tests as needed (such as lung function tests, genetic tests, and tests to match your tissues with a possible donor if a stem cell transplant is being considered)

Children who have thalassemias should receive yearly checkups to monitor their growth and development. The checkups include a physical exam, including a height and weight check, and any necessary tests.

Take Steps To Stay Healthy

Take steps to stay as healthy as possible. Follow a healthy eating plan and your doctor’s instructions for taking iron supplements.

Get vaccinations as needed, especially if you’ve had your spleen removed. You may need vaccines for the flu, pneumonia, hepatitis B, and meningitis. Your doctor will advise you about which vaccines you need.

Watch for signs of infection (such as a fever) and take steps to lower your risk for infection (especially if you’ve had your spleen removed). For example:

• Wash your hands often.
• Avoid crowds during cold and flu season.
• Keep the skin around the site where you get blood transfusions as clean as possible.
• Call your doctor if a fever develops.

Emotional Issues and Support

If you or your child has thalassemia, you may have fear, anxiety, depression, or stress. Talk about how you feel with your health care team. Talking to a professional counselor also can help. If you’re very depressed, your doctor may recommend medicines or other treatments that can improve your quality of life.

Joining a patient support group may help you adjust to living with thalassemia. You can see how other people who have the same symptoms have coped with them. Talk with your doctor about local support groups or check with an area medical center.

Support from family and friends also can help relieve stress and anxiety. Let your loved ones know how you feel and what they can do to help you.

Some teens and young adults who have thalassemias may have a hard time moving from pediatric care to adult care. Doctors and other health professionals who care for these children might not be familiar with adult issues related to the disorder, such as certain complications.

Also, it might be hard for adults who have thalassemias to find doctors who specialize in treating the disorder. Ask your child’s doctor to help you find a doctor who can care for your child when the time comes to make the switch. Planning and good communication can help this move go smoothly.

What is iron deficiency anemia

Iron deficiency anemia is a condition where a lack of iron in the body leads to a reduction in the number of healthy red blood cells. Red blood cells carry oxygen to the body’s tissues.

Iron deficiency anemia is a common type of anemia and it has many causes – particularly in women, premature or very small babies, children and people on restricted diets. Symptoms are related to the overall decrease in the number of red blood cells (RBCs) and the level of hemoglobin. If the iron deficiency anemia is mild to moderate, there may be no signs or symptoms. In addition to the most common signs and symptoms, there are some that are more unique to iron deficiency and may appear as iron stores in the body are chronically depleted. These may include:

• Brittle or spoon-shaped nails
• Swollen or sore tongue
• Cracks or ulcers at the corners of the mouth
• Difficulty in swallowing
• Craving to eat unusual non-food substances such as ice or dirt (also known as “pica”)

Iron is an essential trace element and is necessary for the production of healthy red blood cells. It is one component of heme, a part of hemoglobin, which is the protein in red blood cells that binds to oxygen and allows red blood cells to transport oxygen throughout the body. If not enough iron is taken in compared to what the body needs, then iron stored in the body begins to be used up. As iron stores are depleted, the body makes fewer red blood cells with decreased amounts of hemoglobin in them, resulting in anemia.

What happens if you don’t get enough iron ?

In the short term, getting too little iron does not cause obvious symptoms. The body uses its stored iron in the muscles, liver, spleen, and bone marrow. But when levels of iron stored in the body become low, iron deficiency anemia sets in. Red blood cells become smaller and contain less hemoglobin. As a result, blood carries less oxygen from the lungs throughout the body.

Symptoms of iron deficiency anemia include tiredness and lack of energy, GI (gastrointestinal) upset, poor memory and concentration, and less ability to fight off germs and infections or to control body temperature. Infants and children with iron deficiency anemia might develop learning difficulties.

Iron deficiency without anemia

Although iron deficiency is not common in the United States, iron deficiency is the most common known form of nutritional deficiency worldwide. It can occur in people who do not eat meat, poultry, or seafood; lose blood; have gastrointestinal diseases that interfere with nutrient absorption; or eat poor diets.Its prevalence is highest among young children and women of childbearing age (particularly pregnant women). In children, iron deficiency causes developmental delays and behavioral disturbances, and in pregnant women, it increases the risk for a preterm delivery and delivering a low-birthweight baby. In the past three decades, increased iron intake among infants has resulted in a decline in childhood iron-deficiency anemia in the United States. As a consequence, the use of screening tests for anemia has become a less efficient means of detecting iron deficiency in some populations. For women of childbearing age, iron deficiency has remained prevalent ⁵⁾.

Iron deficiency has negative effects on work capacity and on motor and mental development in infants, children, and adolescents, and maternal iron deficiency anemia might cause low birthweight and preterm delivery ⁶⁾, ⁷⁾, ⁸⁾. Although iron deficiency is more common in developing countries, a significant prevalence was observed in the United States during the early 1990s among certain populations, such as toddlers and females of childbearing age ⁹⁾.

Centers for Disease Control and Prevention (CDC) has published recommendations to prevent iron deficiency in the United States ¹⁰⁾. To prevent iron deficiency, vulnerable populations should be encouraged to eat iron-rich foods and breast-feed or use iron-fortified formula for infants.

The definition of iron deficiency was an abnormal value for at least two of the following three indicators: serum ferritin, transferrin saturation, and free erythrocyte protoporphyrin. Persons with iron deficiency and a low hemoglobin value were considered to have iron deficiency anemia ¹¹⁾.

The estimated prevalence of iron deficiency was greatest among toddlers aged 1–2 years (7%) and adolescent and adult females aged 12–49 years (9%–16%) ¹²⁾. The prevalence of iron deficiency was approximately two times higher among non-Hispanic black and Mexican-American females (19%–22%) than among non-Hispanic white females (10%).

Complications of iron deficiency anemia

Mild iron deficiency anemia usually doesn’t cause complications. However, left untreated, iron deficiency anemia can become severe and lead to health problems, including the following:

• Heart problems. Iron deficiency anemia may lead to a rapid or irregular heartbeat. Your heart must pump more blood to compensate for the lack of oxygen carried in your blood when you’re anemic. This can lead to an enlarged heart or heart failure.
• Problems during pregnancy. In pregnant women, severe iron deficiency anemia has been linked to premature births and low birth weight babies. But the condition is preventable in pregnant women who receive iron supplements as part of their prenatal care.
• Growth problems. In infants and children, severe iron deficiency can lead to anemia as well as delayed growth and development. Additionally, iron deficiency anemia is associated with an increased susceptibility to infections.

Iron deficiency anemia causes

Iron is stored in your liver, spleen and bone marrow and is vital for mental and physical well-being.

While most of the body’s iron is recycled from red blood cells that have died, a small but essential amount comes from food. (Iron is one of the many minerals found in food.)

Iron deficiency anemia occurs when your body doesn’t have enough iron to produce hemoglobin. Hemoglobin is the part of red blood cells that gives blood its red color and enables the red blood cells to carry oxygenated blood throughout your body.

If you aren’t consuming enough iron, or if you’re losing too much iron, your body can’t produce enough hemoglobin, and iron deficiency anemia will eventually develop.

The reasons for getting iron deficiency anemia include the following.

Loss of iron as a result of blood loss, for example from:

• heavy periods;
• stomach and bowel problems (including ulcers, bowel polyps, hemorrhoids or cancer), which can go unnoticed because the blood loss may be very slow; or
  regular use of medicines that can cause stomach bleeding (for example, aspirin and non-steroidal anti-inflammatory medicines – NSAIDs).

Inadequate intake of iron in the diet to meet the demands of the body, due to:

• lack of iron in the diet over a long period of time (vegetarians and vegans are at increased risk);
• fast growth in children;
• being born early (premature);
• being pregnant — the mother’s iron stores go to her baby; or
• excessive exercise — where the body needs more iron than usual and iron is also lost in sweat.

Inadequate absorption of iron from the gut, due to:

• being unable to absorb iron in the bowel, for example in Crohn’s disease or untreated Celiac disease; or
• surgery that involves removing or bypassing part of the stomach or small bowel (for example, some types of weight loss surgery).

Risk factors of iron deficiency anemia

These groups of people may have an increased risk of iron deficiency anemia:

• Women. Because women lose blood during menstruation, women in general are at greater risk of iron deficiency anemia.
• Infants and children. Infants, especially those who were low birth weight or born prematurely, who don’t get enough iron from breast milk or formula may be at risk of iron deficiency. Children need extra iron during growth spurts. If your child isn’t eating a healthy, varied diet, he or she may be at risk of anemia.
• Vegetarians. People who don’t eat meat may have a greater risk of iron deficiency anemia if they don’t eat other iron-rich foods.
• Frequent blood donors. People who routinely donate blood may have an increased risk of iron deficiency anemia since blood donation can deplete iron stores. Low hemoglobin related to blood donation may be a temporary problem remedied by eating more iron-rich foods. If you’re told that you can’t donate blood because of low hemoglobin, ask your doctor whether you should be concerned.

How Can Iron-Deficiency Anemia Be Prevented ?

Eating a well-balanced diet that includes iron-rich foods may help you prevent iron-deficiency anemia.

Taking iron supplements also may lower your risk for the condition if you’re not able to get enough iron from food. Large amounts of iron can be harmful, so take iron supplements only as your doctor prescribes.

Infants and young children and women are the two groups at highest risk for iron-deficiency anemia. Special measures can help prevent the condition in these groups.

Infants and Young Children

A baby’s diet can affect his or her risk for iron-deficiency anemia. For example, cow’s milk is low in iron. For this and other reasons, cow’s milk isn’t recommended for babies in their first year. After the first year, you may need to limit the amount of cow’s milk your baby drinks.

After age 6 months, start feeding your baby iron-fortified cereals or pureed meats at least twice a day to boost iron intake. After one year, be sure children don’t drink more than 20 ounces (591 milliliters) of milk a day. Too much milk often takes the place of other foods, including those that are rich in iron.

Also, babies need more iron as they grow and begin to eat solid foods. Talk with your child’s doctor about a healthy diet and food choices that will help your child get enough iron.

Your child’s doctor may recommend iron drops. However, giving a child too much iron can be harmful. Follow the doctor’s instructions and keep iron supplements and vitamins away from children. Asking for child-proof packages for supplements can help prevent overdosing in children.

Because recent research supports concerns that iron deficiency during infancy and childhood can have long-lasting, negative effects on brain health, the American Academy of Pediatrics recommends testing all infants for anemia at 1 year of age.

Women and Girls

Women of childbearing age may be tested for iron-deficiency anemia, especially if they have:

• A history of iron-deficiency anemia
• Heavy blood loss during their monthly periods
• Other risk factors for iron-deficiency anemia

The Centers for Disease Control and Prevention (CDC) has developed guidelines for who should be screened for iron deficiency, and how often:

• Girls aged 12 to 18 and women of childbearing age who are not pregnant: Every 5 to 10 years.
• Women who have risk factors for iron deficiency: Once a year.
• Pregnant women: At the first prenatal visit.

For pregnant women, medical care during pregnancy usually includes screening for anemia. Also, your doctor may prescribe iron supplements or advise you to eat more iron-rich foods. This not only will help you avoid iron-deficiency anemia, but also may lower your risk of having a low-birth-weight baby.

You can reduce your risk of iron deficiency anemia by choosing iron-rich foods.

Choose iron-rich foods

Foods rich in iron include:

• Red meat, pork and poultry
• Seafood
• Beans
• Dark green leafy vegetables, such as spinach
• Dried fruit, such as raisins and apricots
• Iron-fortified cereals, breads and pastas
• Peas

Your body absorbs more iron from meat than it does from other sources. If you choose to not eat meat, you may need to increase your intake of iron-rich, plant-based foods to absorb the same amount of iron as does someone who eats meat.

Choose foods containing vitamin C to enhance iron absorption

You can enhance your body’s absorption of iron by drinking citrus juice or eating other foods rich in vitamin C at the same time that you eat high-iron foods. Vitamin C in citrus juices, like orange juice, helps your body to better absorb dietary iron.

Vitamin C is also found in:

• Broccoli
• Grapefruit
• Kiwi
• Leafy greens
• Melons
• Oranges
• Peppers
• Strawberries
• Tangerines
• Tomatoes

How much iron do you need ?

The amount of iron you need each day depends on your age, your sex, and whether you consume a mostly plant-based diet. Average daily recommended amounts are listed below in milligrams (mg). Vegetarians who do not eat meat, poultry, or seafood need almost twice as much iron as listed in the table because the body doesn’t absorb nonheme iron in plant foods as well as heme iron in animal foods.

Most people in America get enough iron. However, certain groups of people are more likely than others to have trouble getting enough iron:

• Teen girls and women with heavy periods.
• Pregnant women and teens.
• Infants (especially if they are premature or low-birthweight).
• Frequent blood donors.
• People with cancer, gastrointestinal (GI) disorders, or heart failure.

Iron deficiency anemia signs and symptoms

The symptoms of iron deficiency anemia are caused by a lack of oxygen being supplied to the tissues.

Iron deficiency anemia signs and symptoms may include:

• Tiredness;
• Weakness;
• Short of breath (especially when exercising);
• Light-headed or dizziness;
• Have headaches or become irritable;
• Extreme fatigue
• Pale skin
• Chest pain, fast heartbeat or shortness of breath
• Cold hands and feet
• Inflammation or soreness of your tongue
• Brittle nails
• Unusual cravings for non-nutritive substances, such as ice, dirt or starch
• Poor appetite, especially in infants and children with iron deficiency anemia

In addition, your skin and the inside of your mouth may be pale.

Older people with anemia may get angina (pain in the chest) because the heart has to work harder to supply enough oxygen to the body.

Signs and symptoms of iron deficiency include the following:

• In the early stages of iron deficiency you may have no symptoms or just mild fatigue.
• You may be more likely to pick up infections.
• Eventually, your nails can become spoon-shaped and brittle, the corners of your mouth may crack, and you may have difficulty swallowing.
• Some people with low iron levels, especially children, may have difficulty with concentration and memory, or have trouble learning. Iron deficiency anemia in children may cause problems with development.
• Some people get cravings for unusual substances, such as ice or earth (soil).

How is iron deficiency anemia diagnosed?

Your doctor will ask about your symptoms and perform a physical examination, looking for signs of anemia and iron deficiency.

If they suspect iron deficiency anemia, they may also ask about your diet and other possible causes.

If your anemia is not severe you may not have any symptoms and may be diagnosed following a routine blood test.

Your doctor will diagnose iron-deficiency anemia based on your medical history, a physical exam, and the results from tests and procedures.

Once your doctor knows the cause and severity of the condition, he or she can create a treatment plan for you.

Mild to moderate iron-deficiency anemia may have no signs or symptoms. Thus, you may not know you have it unless your doctor discovers it from a screening test or while checking for other problems.

Your doctor will do a physical exam to look for signs of iron-deficiency anemia. He or she may:

• Look at your skin, gums, and nail beds to see whether they’re pale
• Listen to your heart for rapid or irregular heartbeats
• Listen to your lungs for rapid or uneven breathing
• Feel your abdomen to check the size of your liver and spleen
• Do a pelvic and rectal exam to check for internal bleeding

Iron deficiency anemia tests

Your doctor will recommend blood tests to determine whether you have iron deficiency anemia, and possibly further tests to work out the cause.

• A complete blood count (CBC) and blood film show the hemoglobin level, plus the number and size of red blood cells. A low hemoglobin plus red blood cells that are smaller than normal and pale in color are features of iron-deficiency anemia.
• Iron studies (including iron, ferritin and transferrin) measure iron and iron stores in the body.

The complete blood count (CBC) measures many parts of your blood.

This test checks your hemoglobin and hematocrit levels. Hemoglobin is an iron-rich protein in red blood cells that carries oxygen to the body. Hematocrit is a measure of how much space red blood cells take up in your blood. A low level of hemoglobin or hematocrit is a sign of anemia.

The normal range of these levels varies in certain racial and ethnic populations. Your doctor can explain your test results to you.

The complete blood count (CBC) also checks the number of red blood cells, white blood cells, and platelets in your blood. Abnormal results may be a sign of infection, a blood disorder, or another condition.

Finally, the complete blood count (CBC) looks at mean corpuscular volume (MCV). MCV is a measure of the average size of your red blood cells. The results may be a clue as to the cause of your anemia. In iron-deficiency anemia, for example, red blood cells usually are smaller than normal.

Other tests may be needed to see if there is any bleeding in your stomach or bowel, or a condition which may be affecting the absorption of iron.

If the CBC results confirm you have anemia, you may need other blood tests to find out what’s causing the condition, how severe it is, and the best way to treat it.

Reticulocyte count. This test measures the number of reticulocytes in your blood. Reticulocytes are young, immature red blood cells. Over time, reticulocytes become mature red blood cells that carry oxygen throughout your body.

A reticulocyte count shows whether your bone marrow is making red blood cells at the correct rate.

Peripheral smear. For this test, a sample of your blood is examined under a microscope. If you have iron-deficiency anemia, your red blood cells will look smaller and paler than normal.

Tests to measure iron levels. These tests can show how much iron has been used from your body’s stored iron.

Tests to measure iron levels include:

• Serum iron. This test measures the amount of iron in your blood. The level of iron in your blood may be normal even if the total amount of iron in your body is low. For this reason, other iron tests also are done.
• Serum ferritin. Ferritin is a protein that helps store iron in your body. A measure of this protein helps your doctor find out how much of your body’s stored iron has been used.
• Transferrin level, or total iron-binding capacity. Transferrin is a protein that carries iron in your blood. Total iron-binding capacity measures how much of the transferrin in your blood isn’t carrying iron. If you have iron-deficiency anemia, you’ll have a high level of transferrin that has no iron.

Other tests. Your doctor also may recommend tests to check your hormone levels, especially your thyroid hormone. You also may have a blood test for a chemical called erythrocyte protoporphyrin. This chemical is a building block for hemoglobin.

Children also may be tested for the level of lead in their blood. Lead can make it hard for the body to produce hemoglobin.

Tests and Procedures for Gastrointestinal Blood Loss

Your doctor may refer you to a gastroenterologist (a specialist in conditions affecting the digestive tract) or surgeon, who may recommend an endoscopy and/or colonoscopy to investigate your digestive tract.

• Endoscopy. Doctors often check for bleeding from a hiatal hernia, an ulcer or the stomach with the aid of endoscopy. In this procedure, a thin, lighted tube equipped with a video camera is passed down your throat to your stomach. This allows your doctor to view the tube that runs from your mouth to your stomach (esophagus) and your stomach to look for sources of bleeding.
• Colonoscopy. To rule out lower intestinal sources of bleeding, your doctor may recommend a procedure called a colonoscopy. A thin, flexible tube equipped with a video camera is inserted into the rectum and guided to your colon. You’re usually sedated during this test. A colonoscopy allows your doctor to view inside some or all of your colon and rectum to look for internal bleeding.

Further investigation of women with heavy periods may involve an ultrasound of the pelvis to determine if there is an underlying cause, such as fibroids in the uterus (womb).

Iron deficiency anemia treatment

Treatment for iron deficiency anemia involves treating the underlying cause of your anemia and replacing iron with iron supplements and a good diet.

Severe iron-deficiency anemia may require a blood transfusion, iron injections, or intravenous (IV) iron therapy. Treatment may need to be done in a hospital.

The goals of treating iron-deficiency anemia are to treat its underlying cause and restore normal levels of red blood cells, hemoglobin, and iron.

Your blood count will be checked regularly to make sure the anemia has not returned.

Iron supplements

You may need iron supplements to build up your iron levels as quickly as possible. Iron supplements can correct low iron levels within months. Supplements come in pill form or in drops for children.

Large amounts of iron can be harmful, so take iron supplements only as your doctor prescribes. Keep iron supplements out of reach from children. This will prevent them from taking an overdose of iron.

Iron supplements are usually given as tablets, but if you need a high dose of iron, you may have an injection into a muscle or intravenous infusion (via a drip into a vein).

Intravenous iron therapy presents some safety concerns. It must be done in a hospital or clinic by experienced staff. Iron therapy usually is given to people who need iron long-term but can’t take iron supplements by mouth. This therapy also is given to people who need immediate treatment for iron-deficiency anemia.

Standard multivitamin tablets do not contain iron and, those that do, are usually labeled as multivitamins with iron. Iron for treatment of iron deficiency is available as various ferrous ion salts (gluconate, sulfate, fumarate), usually in concentrations of 200 to 400 mg per tablet, representing 30 to 100 mg of elemental iron. The typical recommended dose is 100 to 200 mg of elemental iron daily, which may represent 1 to 4 tablets (see Table 1) ¹³⁾.

Table 1. Concentrations of elemental iron in typical iron tablets

Side effects of Iron tablets can include:

• dark or black bowel motions (this is harmless);
• indigestion;
• nausea;
• diarrhea; or
• constipation.

If side effects are troubling you, your doctor may change the tablets or suggest taking a smaller dose more frequently.

Take your tablets as prescribed and keep tablets out of the reach of children (an accidental overdose of iron tablets can be dangerous for children).

Taking your iron supplements

• Take iron tablets on an empty stomach (at least an hour before eating) to increase absorption. However, if you get bad indigestion you should take them with food.
• Don’t take iron supplements with milk, tea or coffee — these can reduce the amount of iron your body absorbs.
• Vitamin C helps with iron absorption – your doctor may recommend taking your tablets with orange juice.
• Wait 2 hours after taking iron tablets before taking other medicines. Some medicines and supplements – including antacids, medicines for gastro-esophageal reflux disease (GERD) and calcium supplements – can reduce iron absorption.
• Keep taking the tablets for at least 3 months or until your doctor tells you to stop. You should take them until well after your hemoglobin is normal.

If you are pregnant you may be given iron tablets. A healthy diet is also recommended.

Children with iron deficiency anemia should be given their iron medicine (usually in liquid form) before meals with orange juice (not milk), as vitamin C increases iron absorption. They should use a straw because liquid iron can discolor the mouth.

Iron deficiency anemia diet

Your doctor may advise you to eat more foods that are rich in iron. The best source of iron is red meat, especially beef and liver. Chicken, turkey, pork, fish, and shellfish also are good sources of iron.

The body tends to absorb iron from meat better than iron from nonmeat foods. However, some nonmeat foods also can help you raise your iron levels. Examples of nonmeat foods that are good sources of iron include:

Iron-fortified breads and cereals

• Peas; lentils; white, red, and baked beans; soybeans; and chickpeas
• Tofu
• Dried fruits, such as prunes, raisins, and apricots
• Spinach and other dark green leafy vegetables
• Prune juice

The Nutrition Facts labels on packaged foods will show how much iron the items contain. The amount is given as a percentage of the total amount of iron you need every day.

Vitamin C

Vitamin C helps the body absorb iron. Good sources of vitamin C are vegetables and fruits, especially citrus fruits. Citrus fruits include oranges, grapefruits, tangerines, and similar fruits. Fresh and frozen fruits, vegetables, and juices usually have more vitamin C than canned ones.

If you’re taking medicines, ask your doctor or pharmacist whether you can eat grapefruit or drink grapefruit juice. Grapefruit can affect the strength of a few medicines and how well they work.

Other fruits rich in vitamin C include kiwi fruit, strawberries, and cantaloupes.

Vegetables rich in vitamin C include broccoli, peppers, Brussels sprouts, tomatoes, cabbage, potatoes, and leafy green vegetables like turnip greens and spinach.

Iron-rich diet

Your body absorbs only a small amount of iron, so it is important to eat a lot of iron-rich foods (meat, fish or poultry, whole or enriched grains) every day. If you don’t eat meat (the best source of iron), make sure you eat plenty of leafy green vegetables, iron fortified foods (such as cereals), eggs, nuts, wholemeal bread and pasta, dried fruit, beans and lentils.

Eating a lot of foods rich in vitamin C (e.g. citrus fruits, kiwi fruit, red capsicum, leafy green vegetables) will help iron absorption.

Limit your milk intake to 500 mL daily in adults. Talk with your doctor, dietitian or community health nurse about other ways to get enough calcium.

Don’t drink tea with meals — it prevents iron absorption.

Your doctor or dietitian can tell you how much iron you need daily. A dietitian can plan a diet for you, and discuss iron intake for vegetarians.

What foods provide iron ?

Iron is found naturally in many foods and is added to some fortified food products. You can get recommended amounts of iron by eating a variety of foods, including the following:

• Lean meat, seafood, and poultry.
• Iron-fortified breakfast cereals and breads.
• White beans, lentils, spinach, kidney beans, and peas.
• Nuts and some dried fruits, such as raisins.

Iron in food comes in two forms: heme iron and nonheme iron. Nonheme iron is found in plant foods and iron-fortified food products. Meat, seafood, and poultry have both heme and nonheme iron.

Heme iron has higher bioavailability than nonheme iron, and other dietary components have less effect on the bioavailability of heme than nonheme iron ¹⁴⁾. The bioavailability of iron is approximately 14% to 18% from mixed diets that include substantial amounts of meat, seafood, and vitamin C (ascorbic acid, which enhances the bioavailability of nonheme iron) and 5% to 12% from vegetarian diets ¹⁵⁾. In addition to ascorbic acid, meat, poultry, and seafood can enhance nonheme iron absorption, whereas phytate (present in grains and beans) and certain polyphenols in some non-animal foods (such as cereals and legumes) have the opposite effect ¹⁶⁾. Unlike other inhibitors of iron absorption, calcium might reduce the bioavailability of both nonheme and heme iron. However, the effects of enhancers and inhibitors of iron absorption are attenuated by a typical mixed western diet, so they have little effect on most people’s iron status.

Several food sources of iron are listed in Table 2. Some plant-based foods that are good sources of iron, such as spinach, have low iron bioavailability because they contain iron-absorption inhibitors, such as polyphenols ¹⁷⁾.

Your body absorbs iron from plant sources better when you eat it with meat, poultry, seafood, and foods that contain vitamin C, like citrus fruits, strawberries, sweet peppers, tomatoes, and broccoli.

Table 2: Selected Food Sources of Iron

* DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers compare the nutrient contents of products within the context of a total diet. The DV for iron is 18 mg for adults and children age 4 and older. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.

Other treatments

For severe iron deficiency anemia, you may need a blood transfusion.

• If you have heavy periods your doctor may be able to suggest medicines (such as the oral contraceptive pill) to reduce blood loss.
• Antibiotics and other medications to treat peptic ulcers
• Surgery to remove a bleeding polyp, a tumor or a fibroid

Prevention

The best way to prevent iron deficiency is to ensure your intake of iron is adequate, especially if you are at increased risk. See your doctor or a dietitian for advice on following an iron-rich diet.

Iron supplements may be recommended to prevent iron-deficiency anemia in people who are unable to get sufficient iron from food.