Page 1026 - Williams Hematology ( PDFDrive )

1000 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 65: Neutropenia and Neutrophilia 1001

endogenous epinephrine, norepinephrine, or cortisol levels. Acute neu- production caused by chromosome 21 trisomy, but the precise mecha-
trophilia occurs in pregnant patients and may be especially notable at nism is unknown. Idiopathic neutrophilic leukocytosis with a negative
the time of entering labor. Acute neutrophilia occurs with induction of family history and a similar condition of hereditary neutrophilia with
general or epidural anesthesia, with all types of surgery, and with other an autosomal dominant pattern of inheritance have been reported 154,155
acute events such as seizures, gastrointestinal hemorrhage, subarach- but are very rare. An inherited activating mutation in the G-CSF recep-
noid hemorrhage, or other internal bleeding. tor (CSF3R) gene induces chronic hereditary neutrophilia. Careful
156
Neutrophilia occurs with many acute bacterial infections. It occurs clinical examination and followup almost always reveal the cause of the
less predictably with infections caused by viruses, fungi, and parasites. neutrophilia.
Many aspects of the complex interactions of microbes with the infected
host are not fully understood. Most patients with Gram-positive infec- Neutrophilia Associated with Drugs
tions, such as pneumococcal pneumonia, staphylococcal abscesses, Many drugs cause neutropenia, but neutrophilia in response to drugs
and streptococcal pharyngitis, have neutrophilia. Infections caused is uncommon except for the well-known effects of epinephrine, other
by Gram-negative bacteria, particularly those resulting in bacteremia catecholamines, and glucocorticoids. Lithium salts cause sustained
157
146
or septic shock, may cause neutropenia or extreme neutrophilia. neutrophilia. The counts return to normal when the drug is discon-
Increased circulating levels of activated complement components, tinued. The drug increases levels of colony-stimulating factor. Cases of
G-CSF, tumor necrosis factor, and interleukin (IL)-1, IL-6, and IL-8 neutrophilia have been reported with ranitidine and quinidine therapy,
may cause this response. Bacterial infections that have an insidious but such reactions are very uncommon.
onset and cause splenomegaly, such as typhoid fever and brucellosis,
characteristically do not show neutrophilia except in the initial or dis-
seminated phase. Miliary tuberculosis is an important cause of leuke- CLINICAL APPROACH TO PATIENTS WITH
moid reactions. Neutrophilia is far less common with viral infections. In NEUTROPHILIA
general, neutrophilia is seen in infections producing substantial tissue In most instances, the finding of neutrophilia, band neutrophils, and
injury, evoked by toxins produced by the infecting organisms. Damage toxic granules in the mature cells can be related to an obvious ongoing
to host tissues also is the presumed mechanism of neutrophilia in ther- inflammatory condition. Often the finding of neutrophilia helps con-
mal burns, electric shock, myocardial infarction, pulmonary embolism, firm the diagnosis of appendicitis, cholecystitis, or bacterial pharyngi-
sickle cell crisis, and systemic vasculitis. tis. When the cause of neutrophilia is not readily apparent, especially if
Many chronic noninfectious conditions cause neutrophilia. Proba- the neutrophilia is associated with fever or other signs of inflammation,
bly the most frequent cause is cigarette smoking. 147,148 Neutrophil counts more subtle infections such as tuberculosis or osteomyelitis should be
of smokers are increased in proportion to the amount of exposure. Neu- considered. In addition, a history of smoking and evidence for a chronic
trophil counts of smokers inhaling two packs of cigarettes per day aver- anxiety state or an occult malignancy should be sought. If neutrophilia
age twice the normal levels. Chronic inflammatory diseases, including is accompanied by myelocytes and promyelocytes, increased basophils,
dermatitis, bronchitis, rheumatoid arthritis, osteomyelitis, ulcerative and unexplained splenomegaly, the diagnosis of a myeloproliferative
colitis, and gout, may cause a persistent neutrophilia. Sweet syndrome disease (e.g., chronic myelogenous leukemia, idiopathic myelofibro-
is an unusual dermatologic condition manifested as intense neutrophil sis, or polycythemia vera) should be considered. Measurement of leu-
accumulation in the skin and persistent neutrophilia. 149 kocyte alkaline phosphatase activity can be a useful screening test in
9
cases of moderate neutrophilia (15 to 25 × 10 /L). Ordinarily the values
Neutrophilia in Association with Cancer or Heart Disease are elevated with inflammation of any cause and in subjects receiving
Neutrophilia is associated with many nonhematologic malignancies, glucocorticoid therapy. The values are low in chronic myelogenous leu-
such as lung and gastrointestinal malignancies, particularly when they kemia and variable with other myeloproliferative neoplasms. Serum
metastasize to the liver and lung. In some cases, tumor cells produce vitamin B levels and B -binding proteins are elevated in both benign
150
12
12
colony-stimulating factors that presumably cause the neutrophilia by neutrophilia and chronic myelogenous leukemia. In unexplained
direct marrow stimulation. Tumor necrosis and superinfections are neutrophilia, testing for the cytogenetic alterations and the BCR gene
other possible mechanisms. Neutrophilia is unusual in brain tumors, rearrangement (Chap. 89) and JAK2 gene mutations (Chap. 84) are
melanoma, prostate cancer, and lymphocytic malignancies. important in the diagnostic evaluation. Chapter 89 discusses the diag-
Neutrophilia is a marker for the occurrence and severity of a vari- nosis of chronic myelogenous leukemia and other chronic myelogenous
ety of illnesses. Neutrophilia is associated with an increased incidence leukemia disorders with prominent neutrophilia.
and severity of coronary heart disease, independent of smoking sta- Epidemiologic studies show an association of neutrophilia with
tus. 151,152 Similarly, elevated white cell counts have been associated with adverse effects of smoking, obesity, coronary artery disease, cere-
increased cancer mortality, independent of smoking history. In patients bral vascular disease and malignancies. 158–162 In myeloproliferative
with cancer, subarachnoid hemorrhage, and other serious inflammatory neoplasms, neutrophilia is a predictor of thrombotic events. 163–165 In
conditions, neutrophilia portends a less favorable prognosis. patients with sickle cell disease, neutrophilia correlates with increased
complications and severity of the disease. 166,167 In these patients, treat-
ment with hydroxyurea lowers the blood neutrophil counts, and has
Hereditary Neutrophilia and Neutrophilia as a Manifestation been shown in randomized trials to reduce some of the complications
of a Hematologic Disorder of the disease. In some inflammatory diseases, glucocorticoids, which
In addition to the myeloproliferative neoplasms, including chronic raise blood neutrophils, and immunosuppressive therapies, which lower
neutrophilic leukemia and neutrophilic chronic myelogenous leukemia blood neutrophils, are used to reduce inflammation; this is because both
(Chap. 89), several unusual hematologic conditions may be associated of these classes of drugs reduce the deployment of neutrophils and other
with neutrophilia. The mechanisms for most of these disorders remain leukocytes to tissue sites of inflammation. For instance, glucocorticoids
obscure. In Down syndrome, transient neonatal leukemoid reactions usually suppress the inflammation of the skin in Sweet syndrome. In
resembling chronic myelogenous leukemia may occur. This type most clinical settings, therapies to reduce the neutrophil count are gen-
153
of neutrophilia may be related to a defect in regulation of neutrophil erally not indicated.

Kaushansky_chapter 65_p0991-1004.indd 1001 9/17/15 6:44 PM