What is neutropenia?

Definition

Neutropenia occurs when the peripheral blood contains an abnormally low number
of circulating neutrophils, a type of white blood cell that helps the body
fight bacterial
infections. Diagnosis is made when a blood test, the absolute
neutrophil count (ANC), is less than 1.5 x 109/liters.

Neutropenia and the Immune System

Neutrophils are essential to the immune system because they help to destroy bacteria. In
homeostasis (physiologic health), the body maintains an
equilibrium between neutrophil production and utilization. When this balance is
disrupted and more neutrophils are needed than are produced, neutropenia
results.

Healthy adults produce about sixty billion neutrophils per day, but only a
small percentage is usually expended. Neutrophils, sometimes called
granulocytes, are produced in the bone marrow and released
through the bloodstream. Neutrophils contain microscopic granules (sacs of
enzymes) that help them kill and digest invading microorganisms through a process
known as phagocytosis. People with neutropenia cannot rid the body of
these foreign organisms and thus become highly susceptible to infection.

Severe Chronic Neutropenia (SCN)

SCN is characterized by abnormalities in neutrophil production and classified
as congenital, cyclic, and chronic idiopathic neutropenia, the causes of which are
thought to be a receptor signaling/postreceptor defect, a regulatory defect, and
faulty immune mechanisms, respectively. SCNs affect the body’s integumentary
system and cause infections in the oropharyngeal (throat), respiratory, and
gastrointestinal mucosa; the hair follicles; and the skin’s glandular
structures.

Kostmann’s syndrome is an inherited disorder that causes significant fever and infection at birth and throughout life. Newborns typically have little evidence of mature neutrophil production and extremely low ANCs (0.1 x 109/liters). People with cyclic neutropenia have recurring three-to-six-day episodes of neutropenia followed by recovery, and are especially prone to fever and infection during extreme neutropenic periods when ANCs can fall as low as 0.1 x 109/liters. In chronic idiopathic neutropenia, ANCs are normal at birth but become lower in time, thus predisposing patients to infection.

Acquired or Secondary Neutropenia

Autoimmune neutropenia occurs when the immune system attacks the body’s own blood neutrophils; diagnosis requires that neutrophil-specific antibodies be present. Many drugs used to treat autoimmune diseases cause bone marrow suppression, compromising blood cell production and increasing the risk for neutropenia.

Chemotherapy-induced neutropenia (CIN) is a serious side effect of cancer
treatment. In chemotherapy, cytotoxic agents destroy bone marrow cells and
strip the body of its natural defenses against infection. Patients who become very
neutropenic may need to halt chemotherapy or have their dosages lowered to prevent
infection. CIN is called febrile neutropenia when fever develops in patients with
ANCs below 500/cubic millimeters. Fever is the body’s response to infection and is
especially troubling in these patients because they do not show the usual signs of
redness, swelling, and pus associated with infection.

Impact

Neutropenia, particularly CIN, results in high morbidity and mortality,
increases medical costs, and lowers quality of life. The challenge is to minimize
the incidence of infection with the judicious use of therapeutic interventions,
such as granulocyte colony stimulating factor (G-CSF) or hematopoietic growth
factor, corticosteroids, and broad-spectrum antibiotics.

Bibliography

“Disorders of Phagocyte Function and Number.” In Hematology: Basic Principles and Practice, edited by Ronald Hoffman et al. 5th ed. Philadelphia: Churchill Livingstone/Elsevier, 2009.

Hadley, Andrew G., and Peter Soothill, eds. Alloimmune Disorders of Pregnancy: Anaemia, Thrombocytopenia, and Neutropenia in the Fetus and Newborn. New York: Cambridge University Press, 2002.

Holland, Steven, et al. “Immunodeficiencies.” In Infectious Diseases, edited by Jon Cohen, William Powderly, and Steven Opal. Philadelphia: Mosby/Elsevier, 2010.

“Infectious Diseases: Neutropenia (Agranulocytosis; Granulocytopenia).” In The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers et al. 18th ed. Whitehouse Station, N.J.: Merck Research Laboratories, 2006.

Provan, Drew, and John Gribben, eds. Molecular Haematology. 2d ed. Malden, Mass.: Blackwell, 2005.