Neutropenia

Neutropenia is an abnormally low number of neutrophils in the blood. Neutrophils serve as the major defense of the body 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 somewhat; when it falls below 500 cells per microliter, the risk of infection increases greatly. Without the key defense provided by neutrophils, a person has problems controlling infections and is at risk of dying from an infection.

What Causes it?

1) Reduced production of neutrophils in the bone marrow can occur in some people with cancer, viral infections such as influenza, bacterial infections such as tuberculosis, or deficiencies of vitamin B₁₂ or folic acid. People who have received radiation therapy that involves the bone marrow may also develop neutropenia. Many drugs, including phenytoin, chloramphenicol, 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.Production of neutrophils in the bone marrow is also affected by a severe disorder called aplastic anemia, in which the bone marrow may shut down production of all blood cells.

2) With some bacterial infections and some drug treatments, neutrophils are destroyed faster than they are produced. Some newborn infants and older children with an autoimmune disease 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.

3) Certain rare hereditary diseases also cause the number of neutrophils to decrease. Congenital cases are generally subcategorized on the basis of associated physical findings and abnormalities in other organ systems. Kostmann’s syndrome (congenital agranulocytosis) is a severe form of congenital neutropenia and the neutrophils are severely reduced from birth. Congenital neutropenia can also be present with other symptoms - for example in Schwachman-Diamond syndrome and Glycogen Storage disease type 1b.

What does it look like?

Neutropenia can develop suddenly over a few hours or days (acute neutropenia), or it can develop gradually and last for months or years (chronic neutropenia). Symptoms which patients experience depend on the level of neutropenia. The lower the neutrophil count, the greater the risk of infection. This risk increases if low neutrophil counts persist for more than three days. Types of infection include otitis media (ear infections), tonsillitis, sore throat, mouth ulcers, gum infections and skin abscesses.

Kostman syndrome patients suffer from severe bacterial infections, such as omphalitis (infection of the navel), pneumonia, skin abscesses or otitis media during their first few months of life. Therefore, in most patients congenital neutropenia is diagnosed early during infancy. In children with autoimmune neutropenia serious infections are uncommon. Children usually 'grow out' of this disorder within two years of diagnosis.

Severe neutropenia can lead to serious problems, which require prompt care and attention as the patient could potentially develop a bacterial, fungal or mixed infection at any time. These infections can be life threatening when the patient is persistently severe neutropenic and it is therefore important that if the patient develops any fever or signs or symptoms of an infection, then he or she should be seen by a doctor as soon as possible and treated with medications(such as antibiotics) to fight the infection.

How is it diagnosed?

When a person has frequent or unusual infections, a doctor may suspect neutropenia and order a complete blood cell 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 those receiving chemotherapy or radiation therapy. When the cause is not known, it must be determined.

Blood tests and then a bone marrow biopsy (which involves taking a small sample of the bone marrow for examination under a microscope) will generally help to decide which sort of neutropenia your child has. By determining whether the number of neutrophil stem cells is decreased and whether these cells are maturing normally, the doctor 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 bloodstream. Congenital neutropenia is distinguished from autoimmune neutropenia of the newborn by its persistence after the first few weeks to months of life and by specific antibody tests. Chronic idiopathic neutropenia is also diagnosed by excluding infectious, malignant and autoimmune disorders.

How is it treated?

The treatment of neutropenia depends on its cause and severity. Drugs that may cause neutropenia are discontinued 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 succumb to infection because their bodies lack the means to fight invading organisms. When these people develop infections, they are generally 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 a person who has neutropenia, is an important sign and indicates that immediate medical attention is needed.

Treatment with granulocyte colony stimulating factors (G-CSFs) is the main option of treatment with severe congenital neutropenia. G-CSFs are artificial versions of natural hormones that drive the bone marrow to produce neutrophils. Many children with congenital neutropenia need G-CSFs every day to keep them free of dangerous infections. Some only need to boost their neutrophils when they get a severe infection. G-CSFs are given by an injection just under the skin using a very small needle. Corticosteroids may help if the neutropenia is caused by an autoimmune reaction. Removing an enlarged spleen may cure the neutropenia involved with hypersplenism. When neutropenia is caused by another disease (such as tuberculosis or leukemia or other cancers), treatment of the underlying disease may resolve the neutropenia. Bone marrow (or stem cell) transplantation may be recommended to treat certain serious causes of neutropenia, such as Kostmann syndrome, aplastic anemia or leukemia.