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Overview of Anemia

By Alan E. Lichtin, MD, Associate Professor;Staff Hematologist-Oncologist, Cleveland Clinic Lerner College of Medicine;Cleveland Clinic

Anemia is a condition in which the number of red blood cells or the amount of hemoglobin (the protein that carries oxygen in them) is low.

Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts of the body. When the number of red blood cells is reduced or the amount of hemoglobin in them is low, the blood cannot carry an adequate supply of oxygen. An inadequate supply of oxygen in the tissues produces the symptoms of anemia.


The causes of anemia are numerous, but most can be grouped within three major mechanisms that produce anemia:

  • Blood loss (excessive bleeding)

  • Inadequate production of red blood cells

  • Excessive destruction of red blood cells

Anemia may be caused by excessive bleeding. Bleeding may be sudden, as may occur in an injury or during surgery. Often, bleeding is gradual and repetitive, typically due to abnormalities in the digestive or urinary tract or heavy menstrual periods. Chronic bleeding typically leads to low levels of iron, which leads to worsening anemia.

Anemia may also result when the body does not produce enough red blood cells. Many nutrients are needed for red blood cell production. The most critical are iron, vitamin B12, and folate (folic acid), but the body also needs trace amounts of vitamin C, riboflavin, and copper, as well as a proper balance of hormones, especially erythropoietin (a hormone that stimulates red blood cell production). Without these nutrients and hormones, production of red blood cells is slow and inadequate, or the red blood cells may be deformed and unable to carry oxygen adequately. Chronic disease also may affect red blood cell production. In some circumstances, the bone marrow space may be invaded and replaced (for example, by leukemia, lymphoma, or metastatic cancer), resulting in decreased production of red blood cells.

Anemia may also result when too many red blood cells are destroyed. Normally, red blood cells live about 120 days. Scavenger cells in the bone marrow, spleen, and liver detect and destroy red blood cells that are near or beyond their usual life span. If red blood cells are destroyed prematurely (hemolysis), the bone marrow tries to compensate by producing new cells faster. When destruction of red blood cells exceeds their production, hemolytic anemia results. Hemolytic anemia is relatively uncommon compared with the anemia caused by excessive bleeding and decreased red blood cell production. Hemolytic anemia may result from disorders of the red blood cells themselves, but more often it results from other disorders that cause red blood cells to be destroyed.

Common Causes of Anemia



Chronic excessive bleeding

Bladder tumors

Cancer in the digestive tract

Heavy menstrual bleeding


Kidney tumors


Polyps in the digestive tract

Ulcers in the stomach or small intestine

Sudden excessive bleeding



A ruptured blood vessel


Decreased red blood cell production

Aplastic anemia

Chronic disorders

Folate deficiency

Iron deficiency



Metastatic cancer

Myelodysplasia (abnormalities in bone marrow tissue)


Multiple myeloma

Vitamin B12 deficiency

Vitamin C deficiency

Increased red blood cell destruction

Autoimmune reactions against red blood cells

An enlarged spleen

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Hemoglobin C disease

Hemoglobin E disease

Hemoglobin S-C disease

Hereditary elliptocytosis

Hereditary spherocytosis

Mechanical damage to red blood cells

Paroxysmal nocturnal hemoglobinuria

Sickle cell disease


More About Some Causes of Anemia





Enlarged spleen

An enlarged spleen traps and destroys too many red blood cells.

The disorder that caused the spleen to enlarge is treated.

Sometimes the spleen must be removed surgically.

Symptoms tend to be mild.

Often, an enlarged spleen also traps platelets and white blood cells, thus reducing their number in the bloodstream.

Mechanical damage to red blood cells

Abnormalities in blood vessels (such as an aneurysm), an artificial or damaged heart valve, or extremely high blood pressure can break normal red blood cells apart.

The cause of the damage is identified and corrected.

The kidneys eventually filter the damaged red blood cells out of the blood but may be damaged by them.

The spleen also filters the damaged red cells out of the blood.

Paroxysmal nocturnal hemoglobinuria

The immune system destroys red blood cells.

Hemoglobin from these damaged cells is concentrated in urine during the night, resulting in dark, reddish urine in the morning.

Corticosteroids and a new drug, eculizumab, help relieve symptoms

People with blood clots may need to take an anticoagulant.

People may have severe stomach cramps and clotting in the large veins of the abdomen and legs.

Symptoms often occur in episodes (paroxysmally).

Hereditary spherocytosis

Red blood cells become misshapen and rigid, getting trapped and destroyed in the spleen.

Treatment is usually not needed, but severe anemia may require removal of the spleen.

This hereditary disorder can also cause bone abnormalities, such as a tower-shaped skull.

Hereditary elliptocytosis

Red blood cells are oval or elliptical in shape rather than the normal disk shape.

Severe anemia may require removal of the spleen.

The anemia is usually mild and requires no treatment.

Red blood cell enzyme abnormalities

Glucose-6-phosphate dehydrogenase (G6PD) deficiency: The G6PD enzyme is missing from red blood cell membranes, making cells more fragile.

Pyruvate kinase (PK) deficiency, which is usually present at birth (congenital), also makes red blood cells more fragile.

In G6PD deficiency, anemia can be prevented by avoiding things that trigger it, such as drugs.

In PK deficiency, some people may benefit from removal of the spleen.

G6PD deficiency is a hereditary disorder that almost always affects males.

About 10% of black males and a smaller percentage of white people of Mediterranean origin have G6PD deficiency.

Pyruvate kinase deficiency is rare.

Symptoms and Diagnosis

Symptoms vary depending on the severity of the anemia and how rapidly it develops. Some people with mild anemia, particularly when it develops slowly, have no symptoms at all. Other people may experience symptoms only with physical exertion. More severe anemia may produce symptoms even when people are resting. Symptoms are more severe when mild or severe anemia develops rapidly, such as with bleeding that occurs when a blood vessel ruptures.

Mild anemia often causes fatigue, weakness, and paleness. In addition to these symptoms, more severe anemia may produce faintness, dizziness, increased thirst, sweating, a weak and rapid pulse, and rapid breathing. Severe anemia may produce painful lower leg cramps during exercise, shortness of breath, and chest pain, especially if people already have impaired blood circulation in the legs or certain types of lung or heart disease.

Sometimes anemia is detected before people notice symptoms when routine blood tests are done.

Low levels of hemoglobin and a low hematocrit (the percentage of red blood cells in the total blood volume) found in a blood sample confirm the anemia. Other tests, such as examining a blood sample under a microscope and, less often, examining a sample taken from the bone marrow, help determine the cause of the anemia.

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