Anemia occurs when the number of red blood cells (RBC) and/or the hemoglobin contained in these cells fall below normal. Red blood cells and their hemoglobin are needed for the transport and delivery of oxygen from the lungs to other parts of the body. When there is not enough oxygen available, many tissues and organs in the body can be adversely affected. Anemia may be mild, moderate, or severe, depending on the degree of decrease in red blood cell count and/or hemoglobin levels . It is a very common condition in men and women of all ages, races and ethnicities. However, certain individuals are at an increased risk of developing anemia. These people are those who are fed with diets poor in iron and vitamins,kidney disease, diabetes, cancer, inflammatory bowel disease , family history of hereditary anemia, tuberculosis or HIV patients, people with significant blood loss due to injury or surgery.
Generally, there are two main causes of anemia:
- Deterioration or decrease in the production of red blood cells, as in iron deficiency, vitamin B deficiency, or aplastic anemia
- Shortened lifespan and increased destruction of red blood cells, as in hemolytic anemia
There are several different types of anemia and different causes. The most common types are summarized in the Table below. Click on the links and learn more about each.
Type of anemia
There are several different types of anemia and different causes. The most common types are summarized in the Table below. Click on the links and learn more about each.
Type of anemia Definition Causes Iron deficiency Iron deficiency leads to a decrease in the amount of hemoglobin. Low hemoglobin levels also lead to a decrease in normal red blood cells. Blood loss, iron deficiency, poor absorption of iron Pernicious Anemia and Vitamin B Deficiency
The deficiency of B vitamins does not allow red blood cells to grow and then divide as they do during their normal development, leading to a decrease in the production of these cells.
Intrinsic factor deficiency, diet low in B vitamins, decreased absorption of B vitamins Aplastic Decreased production of cells produced by the bone marrow, including red blood cells Cancer treatment, exposure to toxins, autoimmune disorders, viral infections hemolytic Circulating red blood cells live shorter than their normal 120-day life. This leads to a decrease in their numbers. Hereditary causes include sickle cell anemia, thalassemia, other causes include transfusion reaction, autoimmune disease and use of certain drugs (penicillin) Anemia of chronic diseases In the long term, various ailments can cause decreased production of red blood cells. Kidney disease, diabetes, tuberculosis or HIV
Anemia can be acute or chronic. Chronic anemia develops slowly with long-lasting diseases such as diabetes, chronic kidney disease, or cancer. In these diseases, anemia may not become evident as the symptoms are masked by the underlying disease. In chronic diseases, anemia can often be overlooked for a while. Sometimes it can be detected during tests or examinations for other conditions.
Anemia may occur during acute attacks, as in certain hemolytic anemia in which a significant number of red blood cells are destroyed. Signs and symptoms can become evident in a very short time , and the cause can be determined as a result of physical examination, medical history and tests.
Symptoms and signs
Although different types of anemia have different causes, the signs and symptoms can be very similar. Mild to moderate forms of anemia may cause few symptoms. The most common symptoms:
- A general feeling of tiredness and weakness
- energy loss
As the anemia worsens, headache, dizziness, cold and numbness in the hands and/or feet, pale face, shortness of breath, rapid and irregular heartbeat, and chest pain may develop.
Complete blood count (Hemogram)
Anemia can be detected for the first time with a Complete Blood Count requested during a health examination or tests for other conditions. It is also often requested as part of the annual examinations. The complete blood count is a routine test that gives the number and relative proportion of each type of different blood cell found in your bloodstream. It gives your doctor information about the size, shape and relative maturity of the blood cells present in your blood at the time.
Blood smear preparation (Peripheral smear) and Formula leukocyte
If the complete blood count results indicate anemia, then a Blood Smear Preparation or a Formula Leukocyte may be done. The results of these tests can give clues about the causes of anemia. Several other tests may also be done to help identify the cause of anemia and guide treatment. For more information, see the individual discussion of the different types of anemia.
Iron Deficiency Anemia
Iron deficiency anemia is the most common cause of anemia. Disease symptoms are associated with a general decrease in red blood cells and/or hemoglobin levels. Most common signs and symptoms
- fatigue, feeling tired
- energy loss
Symptoms more typical of iron deficiency, which can occur when the body’s iron stores are increasingly depleted, are brittle and spoon-shaped nails, swollen and painful tongue, cracks or ulcerations at the corners of the mouth, and an urge to eat unusual, non-nutritive substances such as ice and dirt (“pica disease”). Also known as disease symptoms are present.
Iron is an essential element for the production of healthy red blood cells. It forms part of the heme component of hemoglobin, a protein that binds to oxygen in red blood cells and enables these cells to carry oxygen throughout the body. When iron is not taken in sufficient amounts according to the body’s needs, the iron stored in the body begins to be used. When iron stores are depleted, fewer red blood cells are made. After all, low amounts of hemoglobin in them lead to anemia.
Some of the causes of iron deficiency are:
- Bleeding – If there is excessive bleeding or prolonged (chronic) bleeding continues, the body may not be able to absorb or store enough iron to form enough hemoglobin and/or red blood cells to replace what has been lost. Although iron deficiency in women may be due to heavy menstrual bleeding, the cause of bleeding in older women and men is usually diseases of the intestines such as ulcers and cancer.
- Deficiency in the diet – Iron deficiency can simply be due to not getting enough iron in the diet. The body needs more iron in children and especially pregnant women. Pregnant and lactating women often develop iron deficiency because the baby needs plenty of iron for growth. Iron loss can cause low birth weight babies and premature birth. These complications are tried to be prevented by routinely giving iron supplements to women before and during pregnancy. Babies breastfed by women with iron deficiency are prone to iron deficiency anemia.
- Absorption problem- In certain diseases, the absorption of iron in food from the gastrointestinal tract (GI) is adversely affected and may lead to anemia over time. These diseases include Celiac disease and Crohn’s disease.
Initial blood tests typically include a complete blood count (Hemogram) . Possible outcomes:
- Hemoglobin (Hb)- may be normal in the early stage of the disease, but will decrease as the anemia worsens.
- Red blood cell indices- red blood cells may be of normal size and color in the early stage (normocytic, normochromic), while as anemia progresses, these cells gradually become smaller (microcytic) and pale (hypochromic).
- The average size (MCV) of red blood cells may decrease.
- The mean amount of hemoglobin (MCH) in red blood cells may decrease.
- Increased variability in the size of red blood cells (red blood cell distribution width (RDW))
A blood smear will show smaller and paler red blood cells than normal, may show differences in the size of the red blood cells (anisocytosis) and differences in their shape (poikilocytosis).
If your doctor suspects that your anemia is due to iron deficiency, he or she may perform several confirmatory tests to confirm iron deficiency. These tests may include:
- Serum iron – the level of iron in your blood is usually low
- Ferritin – reflects the amount of iron stored in your body and is usually at low levels. It is the most specific test to identify iron deficiency anemia unless infection or inflammation is present.
- Total iron binding capacity (TIBC) and transferrin – the amount of protein that carries iron through the blood, will increase.
Other tests and procedures may be performed if iron deficiency is thought to be due to abnormal blood loss, such as with prolonged bleeding from the gastrointestinal (GI) tract. Lab tests that can detect GI bleeding include:
- Fecal occult blood test (FOBT)
- Stool immunochemical test (FIT)
The Helicobacter pylori test can detect a bacterium that can cause ulcers in the GI tract, possibly due to prolonged bleeding. If any of these tests are positive or a GI bleeding is strongly suspected, procedures such as endoscopy or colonoscopy may be performed to locate the bleeding so that it can be treated .
Treatment of iron deficiency typically includes iron supplements. If iron deficiency is suspected to be caused by abnormal blood loss, additional testing is often needed to determine the cause of the bleeding. Anemia usually resolves when the underlying cause is found and treated.
Pernicious Anemia and Other Vitamin B Deficiencies
Pernicious anemia is a condition in which the body cannot produce enough of a substance called “intrinsic factor”. Intrinsic factor is a protein produced by the stomach wall cells ( parietal cells ), which binds to vitamin B12 and ensures its absorption from the small intestines . Vitamin B12 is important in the production of red blood cells. In the absence of sufficient intrinsic factor, the body cannot absorb vitamin B12 from food. As a result, anemia occurs as a sufficient number of red blood cells cannot be produced. In addition to intrinsic factor deficiency, other causes of vitamin B12 deficiency and anemia are low vitamin B12 in foods, surgical reasons, some medications, digestive disorders (Celiac Disease)., Crohn’s Disease) and infections are factors that negatively affect the absorption of the vitamin. Among them, the most common cause of disease symptoms is pernicious anemia.
Vitamin B12 deficiency can lead to nervous system disorders as well as general anemia symptoms. Possible complaints:
- weakness or tiredness
- numbness and tingling initially felt in the hands and feet
Additional signs of illness may include muscle weakness, slowed reflexes, loss of balance, and unsteady gait. In severe cases, confusion, memory loss, depression and/or dementia can be seen.
Folic acid is another B vitamin. Deficiency of this vitamin can also lead to anemia. Folic acid, also known as folate, is found in many foods, especially green leafy vegetables. Folic acid is needed during pregnancy for the normal development of the brain and spinal cord . It is important for women considering pregnancy to take additional folate before becoming pregnant and throughout pregnancy to avoid folate deficiency. A folate deficiency that may develop in the early stages of pregnancy can cause problems in the development of the baby’s brain and spinal cord.
Anemia caused by vitamin B12 or folate deficiency is sometimes called “macrocytic” or “megaloblastic” anemia because the red blood cells are larger than normal. Because a lack of these vitamins does not allow red blood cells to grow and then divide normally, these cells are larger. It ultimately leads to a reduction of abnormally large red blood cells and anemia.
Initially, signs of anemia will be investigated by complete blood count (Hemogram) and formula leukocytes . In pernicious anemia or vitamin B12 deficiency, these tests usually give the following results:
- low hemoglobin level
- Mean cell volume (MCV), one of the red blood cell indicators, was frequently elevated.
- Abnormally large red blood cells will be seen on blood smear preparations.
Like vitamin B12 deficiency, folic acid deficiency can cause the same changes in the size of hemoglobin and red blood cells. If your anemia is thought to be due to pernicious anemia, or a lack of dietary B12 or folate, additional tests are usually done to make a diagnosis. Some of these tests are:
- Vitamin B12 level – In case of vitamin B12 deficiency, the blood level may decrease.
- Folic acid level – Blood level may decrease in this B vitamin deficiency
- Methylmalonic acid (MMA) level – may be elevated in vitamin B deficiency
- Homocysteine - Levels may be elevated in folate or vitamin B deficiency.
- Reticulocyte count – usually low
- Antibodies to intrinsic factor or parietal cell antibodies may be present in pernicious anemia.
Sometimes a bone marrow aspiration may be performed. It may show that the cells that will mature into red blood cells (precursor cells) in the future are larger than normal.
The treatment of these disorders is to replace the missing vitamin. If the deficiency is due to the inability of the vitamin to be absorbed from the digestive tract, the vitamin can be injected. Treating the underlying cause, such as a digestive system disorder or infection, can help relieve anemia.
See Vitamin B12 and Folate Deficiency for more information .
Aplastic anemia is a rare disease characterized by a decrease in the number of all types of blood cells made in the bone marrow. Normally, the bone marrow produces enough new red (RBC) and white blood cells (WBC-leukocytes) and platelets (platelets) for the body to function normally. Each type of cell enters the bloodstream and ends its life after a certain time. For example, the normal lifespan of red blood cells (RBC-erythrocyte) is about 120 days. If the bone marrow cannot produce enough blood cells to replace those that have completed its life, it can lead to many symptoms, including symptoms of anemia.
Symptoms of aplastic anemia may appear suddenly or develop more slowly. Initially, some general symptoms may occur due to a decrease in the number of red blood cells common to different types of anemia. These symptoms are:
- Fatigue, feeling tired
- energy loss
Some additional signs and symptoms that occur in aplastic anemia are due to a decrease in the number of platelets:
- prolonged bleeding
- frequent nosebleeds
- bleeding gums
- bruising easily
or it may be due to a decrease in white blood cells:
- increase in the number and severity of infections
Causes of aplastic anemia are usually associated with damage to stem cells in the bone marrow responsible for the production of blood cells . Some of the factors that are associated with bone marrow damage and can lead to aplastic anemia are:
- exposure to toxic substances such as arsenic, benzene, or pesticides
- cancer treatment (radiation or chemotherapy)
- autoimmune disorders such as lupus or rheumatoid arthritis
- viral infections such as hepatitis , EBV , HIV , CMV , or parvovirus B19 infections
Rarely, aplastic anemia is due to an inherited (genetic) disorder such as Fanconi anemia.
Laboratory Tests A complete blood count (Hemogram)
, the initial test for anemia, can reveal many abnormal results:
- Decreased hemoglobin and/or hematocrit values
- Decreased red (RBC) and white blood cells (WBC)
- Decreased platelet count
- Red blood cell indicators are usually normal.
- The formula shows a decrease in most of the blood cells except leukocyte lymphocytes.
Some additional tests to help determine the type and cause of anemia:
- Reticulocyte count – usually low.
- Erythropoietin – usually increased in aplastic anemia.
- Bone marrow aspiration will show a reduction in the number of all mature cell types.
- Hepatitis, EBV, CMV infection tests to help determine the cause
- Tests for arsenic ( a heavy metal ) and other toxins
- Iron tests and vitamin B12 tests can be done to exclude other causes .
- Antibody tests, such as the ANA test, are done to determine if the cause is autoimmune disease .
A physical examination or a complete medical history may reveal possible causes of aplastic anemia, such as exposure to toxins or certain drugs (eg, chloramphenicol) or prior cancer treatment. Some cases of aplastic anemia cause temporary and some permanent damage to the bone marrow. Treatment depends on the cause. Reducing or eliminating exposure to certain toxins or drugs can help with the disease. Medications may be given to stimulate the bone marrow, treat infections, or suppress the immune system in autoimmune diseases. In severe cases, blood transfusions and bone marrow transplantation may be required.
Rarely, anemia is due to problems that cause red blood cells (RBCs) to die or be destroyed prematurely. Normally, red blood cells live in the blood for about 4 months. In hemolytic anemia, the lifespan of these cells is shortened, to only a few days. Since the bone marrow is unable to rapidly and sufficiently produce new red blood cells to replace those destroyed, the number of these blood cells decreases, resulting in a reduced capacity to supply oxygen to body tissues. This leads to the appearance of typical signs of anemia:
- weakness and/or fatigue
- energy loss
Depending on the cause, different forms of hemolytic anemia can become chronic and take a long time to develop throughout life. May cause acute signs and symptoms . Its various forms can have very different signs and symptoms. For more information on the different types of anemia, see the discussion items below.
The different causes of hemolytic anemia fall into two main categories:
- In inherited forms, a gene or genes passed from one generation to the next lead to the formation of abnormal red blood cells or hemoglobin.
- Acquired forms caused by non-hereditary factors lead to premature destruction of red blood cells.
Hereditary Hemolytic Anemia
The two most common causes of hereditary hemolytic anemia are sickle cell anemia and thalassemia (Mediterranean anemia).
Sickle cell anemia has a characteristic that causes minor problems (you carry a mutated gene from your mother or father (only one)) or a “disease” with severe clinical problems (when you carry a mutated gene from your parents (both)) leads to Red blood cells (RBCs) are malformed, unstable ( leading to hemolysis ) and can clog blood vessels, causing pain and anaemia. Especially newborns are scanned. Sometimes screening tests are done on amniotic fluid samples prior to delivery. Follow-up tests with different forms of hemoglobin can be done to confirm the diagnosis . Treatment is usually arranged according to the type, frequency and severity of the disease symptoms.
thalassemiais an inherited abnormality of hemoglobin production that causes small red blood cells to form, similar to those seen in iron deficiency. In its most severe form, the lifespan of red blood cells is shortened. In its milder forms, anemia is usually absent or mild. It can be detected by the presence of small red blood cells in a routine complete blood count. This genetic disease is commonly found in people of Mediterranean, African, and Asian descent. The defect in production may involve one or both of the alpha and beta protein chains of hemoglobin. Accordingly, the disease is called alpha or beta thalassemia. The “beta minor” form occurs when a person inherits both normal and beta thalassemia genes. It does not give any symptoms and causes only a mild anemia. “Beta major” can cause jaundice and severe anemia
Other less common types of hemolytic anemia:
- Hereditary spherocytosis – the form that can be seen on a blood smear and causes abnormally shaped red blood cells
- Hereditary elliptocytosis – another cause of abnormally shaped red blood cells seen on a blood smear
- Glucose -6-phosphate dehydrogenase ( (G6PD) deficiency – G6PD is an enzyme essential for the survival of red blood cells. Its deficiency can be recognized by a test that looks for its activity .
- Pyruvate kinase deficiency – pyruvate kinase is another enzyme important for the survival of red blood cells. Deficiency can be determined by a test investigating its activity.
Because some of these inherited forms may have mild symptoms, routine Complete blood count (Hemogram) and blood smear preparation may reveal for the first time various abnormal results that provide clues as to the causes of anemia. Then, follow-up tests are usually applied to diagnose the disease. Some of these tests are:
- Tests for different forms of hemoglobin , such as hemoglobin electrophoresis
- DNA analysis – although not routinely performed , this test can be used to help diagnose different forms of hemoglobin and mediterranean anemia and determine carrier status.
- G6PD test – used to detect deficiency of this enzyme.
- Osmotic fragility test – detects whether red blood cells (RBC) are more fragile than normal, may be found in hereditary spherocytosis disease.
Although these genetic disorders cannot be cured, symptoms that often occur as a result of anemia can be alleviated with treatment if necessary.
Acquired Hemolytic Anemia
Some of the conditions and factors associated with acquired forms of hemolytic anemia are given below:
- Autoimmune disorders – Diseases in which the body creates antibodies against its own red blood cells . How it is formed is unknown.
Treatment of anemia due to chronic conditions usually requires identifying and/or curing the underlying disease. Blood transfusions can be done to cure the condition in a short time.
- Blood transfusion (transfusion) reaction – Blood donor-recipient incompatibility. Although it occurs very rarely, serious complications can occur when it occurs.
Anemia Caused by Chronic Diseases
Chronic (long-term) diseases can cause anemia. Anemia caused by chronic diseases often goes undetected unless a routine test, such as a complete blood count, shows abnormal results . Several follow-up tests can be used to identify the underlying cause. Many chronic diseases can cause anemia. Some examples:
- Kidney disease – Blood cells are produced in the bone marrow in response to the hormone erythropoietin, mainly made by the kidneys . Chronic kidney disease can cause very little production of this hormone and anemia. Anemia can be treated with erythropoietin injections.
- Inflammatory conditions- In the presence of chronic disease that stimulates the body’s inflammatory system, the bone marrow’s ability to respond to erythropoietin decreases. For example , rheumatoid arthritis (joint rheumatism : a severe autoimmune joint disease in which the body attacks its own joints) can cause anemia by this mechanism.
- Other diseases that can cause anemia, such as inflammatory conditions, include chronic infections (eg HIV or tuberculosis , TB), cancer, and cirrhosis .
Several tests may be used to identify the underlying cause, following abnormal results from initial tests such as complete blood count and blood smear preparation . Some of these tests may include:
- Reticulocyte count
- Complete metabolic panel (CMP)
- Inflammation tests such as CRP
- Tests for infections such as HIV and Tuberculosis.