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Neutropenia ˌn(y)ü-trə-ˈpē-nē-ə

(Agranulocytosis; Granulocytopenia)

By Mary Territo, MD, University of California, Los Angeles

Neutropenia is an abnormally low number of neutrophils (a type of white blood cell) in the blood.

  • Neutropenia, if severe, significantly increases the risk of life-threatening infection.

  • Neutropenia is often a side effect of the treatment of cancer with chemotherapy or radiation therapy.

  • Doctors suspect neutropenia in people who have frequent or unusual infections.

  • A blood sample is used to make the diagnosis of neutropenia, and a sample of bone marrow may be needed if the cause is not apparent.

  • Treatment depends on the cause and severity of the disorder and can include drugs to stimulate the body's production of neutrophils.

  • Antibiotics are given if the person has neutropenia and fever or other signs of infection.

Neutrophils are a type of white blood cell that serve as the body's major defense against acute bacterial and certain fungal infections. Neutrophils usually constitute about 45 to 75% of all white blood cells in the bloodstream. When the neutrophil count falls below 1,000 cells per microliter of blood, the risk of infection increases. When it falls below 500 cells per microliter (severe neutropenia), the risk of infection increases greatly. Without the key defense provided by neutrophils, people have problems controlling infections and are at risk of dying from an infection.

Causes of Neutropenia

Neutropenia has many causes, but they fall into two main categories:

  • Neutrophils are used up or destroyed faster than the bone marrow can produce new ones

  • The production of neutrophils in the bone marrow is reduced

Many disorders cause neutrophils to be used up or destroyed. These disorders include certain bacterial infections, some allergic disorders, and some drug treatments (such as drugs used to treat hyperthyroidism). People with an autoimmune disorder can make antibodies that destroy neutrophils and result in neutropenia. People with an enlarged spleen may have a low neutrophil count because the enlarged spleen traps and destroys neutrophils.

Production of neutrophils in the bone marrow can be reduced by cancer, viral infections such as influenza, bacterial infections such as tuberculosis, myelofibrosis, or deficiencies of vitamin B12or folate (folic acid). People who have received radiation therapy that involves the bone marrow may also develop neutropenia. Many drugs, including phenytoin, sulfa drugs, and many drugs used in cancer treatment (chemotherapy), as well as certain toxins (benzene and insecticides) can also impair the bone marrow’s ability to produce neutrophils.

Did You Know...

  • Because neutropenia has no specific symptoms, doctors often do not suspect the disorder unless people have frequent or unusual infections.

Production of neutrophils in the bone marrow is also affected by a disorder called aplastic anemia (in which the bone marrow may shut down production of all blood cells). Certain rare hereditary diseases also cause a decrease in the number of neutrophils.

Symptoms of Neutropenia

Neutropenia can develop

  • Suddenly over a few hours or days in response to certain infections or exposures

  • Gradually

Neutropenia may resolve quickly (when the infection resolves or the exposure stops) and is called acute neutropenia, or it may last for months or years (chronic neutropenia). When neutropenia is caused by drugs, people may have a fever, rash, and swollen lymph nodes.

Because neutropenia itself has no specific symptoms, it is usually diagnosed when an infection occurs. People may develop fever and painful sores (ulcers) around the mouth and anus. Bacterial pneumonia and other severe infections can occur.

In chronic neutropenia, people may not have many symptoms if the number of neutrophils is not extremely low.

In cyclic neutropenia, people can have symptoms that come and go as their white blood cell count rises and falls over time.

Diagnosis of Neutropenia

  • Complete blood count

  • Bone marrow examination

When people have frequent or unusual infections or if people are taking drugs known to cause neutropenia, doctors order a blood test (complete blood count) to make the diagnosis. A low neutrophil count indicates neutropenia.

In many cases, the neutropenia is expected and the cause is known, as in people receiving chemotherapy or radiation therapy. When the cause is not known, it must be determined. And whether the cause is known or not, doctors usually also search for a hidden infection that may have been caused by the neutropenia.

Determination of cause

Doctors ask about drug or toxic exposures and look for infections or other disorders that can cause the neutropenia. They frequently take a sample of bone marrow through a needle. The bone marrow sample is examined under a microscope to determine whether it looks normal, has a normal number of neutrophil stem (precursor) cells, and shows normal development of neutrophils. By determining whether the number of stem cells is decreased and whether these cells are maturing normally, doctors may be able to determine whether the problem lies in faulty production of the cells or whether too many cells are being used or destroyed in the blood. Sometimes, the bone marrow examination indicates whether other diseases, such as leukemia or other cancers, or infections, such as tuberculosis, are affecting the bone marrow.

Evaluation for infection

Because people with neutropenia might not have all the typical symptoms and examination findings of an infection, doctors ask people detailed questions about their symptoms and examine them from head to toe. Tests are done for any concerning findings, for example, if the person has abdominal discomfort, computed tomography (CT) of the abdomen may be done.

Even if there are no specific findings, doctors typically also do urinalysis and urine culture, blood cultures, and a chest x-ray. When doctors do a culture, they take a sample of the material being tested (in this case, urine or blood) and send it to the laboratory to grow bacteria or other organisms that may be present.

Treatment of Neutropenia

  • Antibiotics

  • Drugs to stimulate production of neutrophils

The most important thing is to treat any infection that is found. In people with severe neutropenia, infections can rapidly become serious or fatal. Even if doctors cannot diagnose a specific infection, people who have neutropenia and fever are presumed to have an infection. Such people are given antibiotics effective against common infectious organisms.

The treatment of neutropenia itself depends on its cause and severity. Drugs that may cause neutropenia are stopped whenever possible, and exposures to suspected toxins are avoided.

Sometimes the bone marrow recovers by itself without treatment. The neutropenia accompanying viral infections (such as influenza) may be transient and resolve after the infection has cleared. People who have mild neutropenia generally have no symptoms and may not need treatment.

People who have severe neutropenia can rapidly die as a result of infection because their bodies lack the means to fight invading organisms. When these people develop infections, they are usually hospitalized and immediately given strong antibiotics, even before the cause and exact location of the infection are identified. Fever, the symptom that usually indicates infection in people who have neutropenia, is an important sign that immediate medical attention is needed.

Growth factors called colony-stimulating factors, which stimulate the production of white blood cells by the bone marrow, are sometimes helpful and are given as a injection (under the skin or into a vein).

Corticosteroids may help if the neutropenia is caused by an autoimmune disorder. Antithymocyte globulin or other types of therapy that suppress the activity of the immune system may be given by vein when a disorder such as aplastic anemia is present.

When neutropenia is caused by another disorder (such as tuberculosis or leukemia or other cancers), treatment of the underlying disorder may resolve the neutropenia. Bone marrow (or stem cell) transplantation is not used to treat neutropenia per se, but it may be recommended to treat certain serious causes of neutropenia, such as aplastic anemia or leukemia.

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