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CHAPTER 65 NEUTROPENIA

NEUTROPENIA AND Neutropenia refers to an absolute blood neutrophil count (total leu-
kocyte count per microliter × percent of neutrophils) that is less than
NEUTROPHILIA 2 SD below the normal mean of the population. The terms leukope-
nia, a reduced total white blood cell count, and granulocytopenia,
reduced numbers of blood granulocytes (neutrophils, eosinophils, and
basophils), sometimes are imprecisely used as synonyms for neutropenia.
David C. Dale and Karl Welte Agranulocytosis literally means a complete absence of blood granulo-
cytes, but this term often is used to indicate severe neutropenia, that is,
counts less than 0.5 × 10 /L (0.5 × 10 /μL).
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The concentration of neutrophils in blood is influenced by age,
SUMMARY activity, and genetic and environmental factors (Chap. 2). For chil-
dren from 1 month to 10 years old, neutropenia is defined as a blood
Neutropenia designates a blood absolute neutrophil count that is less than 2 neutrophil count less than 1.5 × 10 /L. For individuals older than age
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SD below the mean of a normal population. Neutropenia can be inherited or 10 years, neutropenia is defined as a count less than approximately 1.8 ×
acquired. It usually results from decreased production of neutrophil precursor 10 /L (see Chap. 7 regarding levels in newborns). Healthy older persons
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cells in the marrow. Neutropenia also can result from a shift of neutrophils have the same blood neutrophil counts as younger individuals (Chap.
from the circulating into the marginated cell pools in the circulation. Less 9). Some racial and ethnic groups, such as Africans, African Ameri-
commonly, neutropenia results from accelerated destruction of neutrophils or cans, and Yemenite Jews, have lower mean neutrophil counts than per-
increased egress of neutrophil from the circulation into the tissues. When neu- sons of Asian or European ancestry (see Chap. 2, Table 2–2). The mean
tropenia is the sole or dominant abnormality, the condition is called “selective” differences in neutrophils are modest and have no recognized health
consequences.
1,2
or isolated” neutropenia, such as severe congenital neutropenia, chronic idio- Severe neutropenia is a predisposing factor for infections. The
pathic neutropenia, or drug-induced neutropenia. Neutropenia can occur in organisms normally are found on the skin, in the nasopharynx, and as
other inherited or acquired marrow failure syndromes, such as severe aplastic part of the intestinal flora. The risk of infections is inversely related to
anemia or Fanconi anemia, in which the condition is a bicytopenia or pan- the severity of the neutropenia (Chap. 24). Individuals with neutrophil
cytopenia. In some diseases, several cell lineages are mildly affected but the counts of 1.0 to 1.8 × 10 /L are at little risk of infection. In general,
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reduction in neutrophil is the most severe, such as Felty syndrome. Neutrope- neutrophil counts between 0.5 and 1.0 × 10 /L are associated with only
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nia may be an indicator of an underlying systemic disease, such as early vitamin slight risk of infection unless other contributing factors are present.
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B or transcobalamin deficiency. Neutropenia, particularly severe neutropenia Individuals with neutrophil counts less than 0.5 × 10 /L are at substan-
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(neutrophil counts <0.5 × 10 /L [500/μL]), increases susceptibility to bacte- tially greater risk, but the frequency of infections varies considerably,
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rial or fungal infections and impairs the resolution of these infections. Therapy depending on the cause and duration of neutropenia. Severe acute neu-
with the hormone primarily responsible for neutrophil production, granulo- tropenia (i.e., developing over a few hours or days) usually is associated
with greater risk of infection than severe chronic neutropenia (usually
cyte colony-stimulating factor, can increase blood neutrophil counts for most present for months or years). Neutropenia resulting from disorders of
types of neutropenia, although whether its administration makes a clinically production that affect early hematopoietic precursor cells (e.g., aplastic
useful impact is dependent on the origin, duration and severity of the neutro- anemia, severe congenital neutropenia) leads to greater susceptibility to
penia. Clinical guidelines have been published on the rational use of the drug. infections than do conditions with adequate neutrophil precursors in
Neutrophilia is an increase in the absolute neutrophil count to a concentra- the marrow and neutropenia attributed to accelerated turnover in the
tion greater than 2 SD above the normal population mean value. Neutrophilia blood (e.g., rheumatoid arthritis, Felty syndrome, autoimmune neutro-
contributes to the inflammatory response and to resolution of infections. penia). For patients made severely neutropenic by cancer chemother-
Inflammatory and infectious diseases are the most frequent causes of neu- apy, the risk is greater when the neutrophils are decreasing than with
trophilia. Bacterial infections usually produce neutrophilia, whereas viral similar counts when neutrophils are increasing. Neutropenia accompa-
infections may not produce neutrophilia or may raise the neutrophil count nied by monocytopenia, lymphocytopenia, or hypogammaglobuline-
only slightly. Solid tumors occasionally engender striking neutrophilia. Hered- mia is more serious than isolated neutropenia. Other factors, such as
the integrity of the skin and mucous membranes, the vascular supply to
itary neutrophilia can be caused by activating mutations within the CSF3R tissues, and the nutritional status of the patient, also influence the risk
gene. When the neutrophil count is very high, it may be referred to as a leu- of infections.
kemoid reaction. The rare neutrophilic variants of chronic myeloid leukemia
and chronic neutrophilic leukemia may result in striking neutrophilia. Demar-
gination of neutrophils or rapid release of neutrophils from a large marrow PATHOPHYSIOLOGIC MECHANISMS
pool may transiently increase the blood neutrophil count. Sustained increased General Mechanisms
require increased production of these cells. Neutropenia occurs because of (1) hypoplastic neutropoiesis, (2) inef-
fective neutropoiesis (resulting from exaggerated apoptosis of late
precursors), (3) accelerated removal or utilization of circulating neu-
trophils, (4) shifts of cells from the circulating to the marginal blood
Acronyms and Abbreviations: ANA, antinuclear antibody; BTH, Bruton tyrosine pools, or (5) a combination of these mechanisms (Fig. 65–1). Some
kinase; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage production disorders are caused by intrinsic abnormalities of hemato-
colony-stimulating factor; Ig, immunoglobulin; IL, interleukin; TRAIL, tumor necrosis poietic progenitor cells (Chap. 83). Other disorders in cell production
factor-related apoptosis-inducing ligand. are caused by extrinsic factors, including changes in the marrow envi-
ronment, such as tumor infiltration, fibrosis, or irradiation (Chap. 45).

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