What is neutropenia?

"Neutropenia" is a condition in which the number of neutrophils in the bloodstream is decreased. Neutrophils are a type of white blood cell also known as polymorphonuclear leukocytes or PMNs. Neutropenia affects the body's ability to fight off infections.

White blood cells are also known as leukocytes. There are five major types of white blood cells:

1. basophils,
   
   
2. eosinophils,
   
   
3. lymphocytes (T-cells and B-cells),
   
   
4. monocytes, and
   
   
5. neutrophils.

Some white blood cells, called granulocytes, are filled with microscopic granules that are little sacs containing enzymes (compounds that digest microorganisms). Neutrophils, eosinophils, and basophils are all granulocytes and are part of the innate immune system with somewhat nonspecific, broad-based activity. They do not respond exclusively to specific antigens, as do the lymphocytes (B-cells and T-cells).

Neutrophils contain enzymes that help the cell kill and digest microorganisms it has engulfed by a process known as phagocytosis. The mature neutrophil has a segmented nucleus (it is often called a 'seg' or 'poly'), while the immature neutrophil has a band-shape nucleus (it is called a band). Neutrophils are made in the bone marrow and released into the bloodstream. The neutrophil has a life-span of about three days.

How is neutropenia defined?

The white blood cell count (WBC) is the number of white blood cells in a volume of blood. The normal range for the WBC varies slightly among laboratories but is generally between 4,300 and 10,800 cells per microliter or cubic millimeter (cmm). The WBC can also be referred to as the leukocyte count and can be expressed in international units as 4.3 x 109to 10.8 x 109 cells per liter. The percentage of the different types of white blood cells in the WBC is called the WBC differential.

The absolute neutrophil count (ANC) is determined by the product of the white blood cell count (WBC) and the fraction of neutrophils among the white blood cells as determined by the WBC differential analysis. For example, if the WBC is 10,000 per microliter and 70% are neutrophils, the ANC would be 7,000 per microliter.

An ANC of less than 1500 per microliter (1500/microL) is the generally accepted definition of neutropenia. Neutropenia is sometimes further classified as:

• mild if the ANC ranges from 1000-1500/microL,
  
  
• moderate with an ANC of 500-1000/microL, and
  
  
• severe if the ANC is below 500/microL.

Some medical terms may be used synonymously with neutropenia, even though their precise definitions are different.

• Leukopenia refers to a reduced number of white blood cells in general, while granulocytopenia refers to a decreased number of all the granulocyte-type blood cells (neutrophils, eosinophils, and basophils).
  
  
• Since neutrophils normally far outnumber the other types of granulocytes, this term is sometimes used to refer to neutropenia.
  
  
• Finally, agranulocytosis literally refers to a complete absence of all granulocytes, but this term is sometimes used to refer to severe neutropenia.

What are the clinical consequences of neutropenia?

Neutropenia results in an increased susceptibility to bacterial infections. The degree of risk depends upon the cause and severity of the neutropenia, the underlying medical condition of the patient, and the presence or absence of bone marrow reserves for the production of neutrophils.

The most common type of infections seen in neutropenic patients are caused by bacteria normally found on the skin (such as Staphylococcus aureus) or from the gastrointestinal and urinary tract. Fungal infections are also more frequent in patients with neutropenia. The infections may be limited to certain areas of the body (commonly the oral cavity, genital area, and skin) or may spread via the bloodstream to the lungs and other organs in severe, prolonged neutropenia.

What causes neutropenia?

Neutropenia can be present (though it is relatively uncommon) in normal healthy individuals, notably in some persons of African or Arabic descent and and Yemenite Jews. Neutropenia may arise as a result of decreased production of neutrophils, destruction of neutrophils after they are produced, or pooling of neutrophils (accumulation of the neutrophils out of the circulation).

Neutropenia may arise as a result of numerous medical conditions:

• Infections (more commonly viral infections, but also bacterial or parasitic infections). Examples include: HIV, tuberculosis, malaria, Epstein Barr virus (EBV);
  
  
• Medications that may damage the bone marrow or neutrophils, including cancer chemotherapy;
  
  
• Vitamin deficiencies (megaloblastic anemia due to vitamin B12 and/or folate deficiency);
  
  
• Diseases of the bone marrow such as leukemias, myelodysplastic syndrome, aplastic anemia, myelofibrosis;
  
  
• Radiation therapy;
  
  
• Congenital (inborn) disorders of bone marrow function or of neutrophil production, for example, Kostmann syndrome;
  
  
• Autoimmune destruction of neutrophils (either as a primary condition or associated with another disease such as Felty's syndrome) or from drugs stimulating the immune system to attack the cells
  
  
• Hypersplenism, which refers to the increased sequestration and/or destruction of blood cells by the spleen

How is neutropenia diagnosed?

Neutropenia is diagnosed by a blood cell count performed on a sample of blood removed from a vein. To determine the specific cause of neutropenia in a given situation, other tests may be required. Sometimes a bone marrow biopsy may be required to diagnose the specific cause of neutropenia.

How is neutropenia treated?

Treatment of neutropenia is based upon the underlying cause, severity, and the presence of associated infections or symptoms as well as the overall health status of the patient. Obviously, treatment must also be directed toward any underlying disease process. Treatments that directly address neutropenia may include (note that all of these treatments may not be appropriate in a given setting):

• antibiotic and/or antifungal medications to help fight infections;
  
  
• administration of white blood cells growth factors (such as recombinant granulocyte colony-stimulating factor (G-CSF, filgrastim) in some cases of severe neutropenia;
  
  
• granulocyte transfusions; or
  
  
• corticosteroid therapy or intravenous immune globulin for some cases of immune-mediated neutropenia.

Preventive measures may also be implemented in neutropenic patients to limit risk of infections. These measures might include strict attention to hand washing, use of private rooms, or in some cases, use of gloves, gowns, and/or face masks by caregivers.

Neutropenia At A Glance

• Neutropenia is a condition in which the number of neutrophils (a type of white blood cell) in the bloodstream is decreased, affecting the body's ability to fight off infections.
  
  
• Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500 per microliter (1500/microL)
  
  
• Neutropenia may be caused by or associated with numerous medical conditions
  
  
• Most infections that occur as a result of neutropenia are due to bacteria that are normally present on the skin or in the gastrointestinal or urinary tract.
  
  
• Treatment depends upon the cause and severity of he condition as well as the underlying disease state responsible for the neutropenia.

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