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White blood cells, or leukocytes, are part of the innate immune
system. They are one of the body’s major defenses in preventing
and combating infection. The most common types of leukocytes are
lymphocytes, monocytes, and granulocytes. This chapter will deal
primarily with granulocytes. These cells are derived from stem cells
in the bone marrow and have diverse functions. The most common of
the leucocytes is the neutrophil. Deficiency of neutrophils, called neutropenia, is
one of the most common hematologic abnormalities during childhood
and when severe can result in life-threatening infection.
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The absolute neutrophil count and the relative proportions of
neutrophils to lymphocytes vary with age. At birth, neutrophils
predominate but rapidly decrease during the first few days of life.
During infancy, neutrophils comprise approximately 20% to
30% of the circulating white blood cell population. By
5 years of age, neutrophil and lymphocyte counts are equal, and
by puberty, adult proportions of approximately 70% are reached.
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Neutropenia is defined by an absolute decrease in the absolute
number of circulating mature (segmented) and band forms of neutrophils,
which can be determined by calculating the absolute neutrophil count
(ANC). The ANC is calculated by multiplying the total white blood
cells (WBC) obtained from the complete blood count (CBC) by the
combined percentage of segmented neutrophils and bands from the
differential. The normal resting ANC in the general population ranges
between 1500 and 8000 cells/cm3 for Caucasian
children over 6 years of age, while 30% of African American
children have an ANC as low as 1000 cells/μl.
Based on the ANC, neutropenia can be classified as mild (ANC between
1000–1500 cells/μl), moderate
(ANC between 500–1000 cells/μl),
or severe (ANC < 500 cells/μl). Neutropenia
is associated with an increased chance of developing infections. However,
only patients with severe neutropenia are likely to develop life-threatening infections.
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Patients with neutropenia are most frequently infected with endogenous
flora, Staphylococcus aureus, and gram-negative
organisms. Susceptibility to bacterial infections varies even in
the presence of severe neutropenia. Some patients with chronic neutropenia
syndromes with an ANC less than 200 cells do not develop life-threatening
infections, while neutropenia induced by immunosuppressive drugs,
particularly in conjunction with a malignancy, is associated with
higher rates of severe infections, probably due to the additional
loss of cellular immunity. Severe neutropenia is associated with
skin and soft-tissue infections, gingivitis, stomatitis, pneumonia,
and septicemia. However, isolated neutropenia is not associated
with an increased risk for parasitic, viral, or fungal infections. Acute
neutropenia arises when neutrophils are being employed and production
is limited. Chronic neutropenia lasting months to years often evolves
from impaired production or excessive splenic sequestration. Neutropenia
may commonly occur from factors extrinsic to marrow myeloid cells
or less frequently as an acquired disorder of myeloid and stem cells.
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Classification
of Primary Neutropenias
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The inherited disorders of bone marrow production, characterized by
selective loss of neutrophil production without accompanying congenital
anomalies, are diagnosed by clinical and laboratory features and
by genetic testing (Table 441-1).1 Many
of the inherited forms of congenital neutropenia fall into a category
of ...