Page 1020 - Williams Hematology ( PDFDrive )

994 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 65: Neutropenia and Neutrophilia 995

parenteral nutrition, with a history of gastrectomy, and in malnourished antigens can be identified on neutrophils and neutrophil precursors
children 86–88 and the bicytopenia or tricytopenias with a marrow show- with monoclonal antibodies. The clearest associations of autoantibodies
ing dysplastic precursors can masquerade as myelodysplastic syndrome. and neutropenia are with NA-1 and NA-2. 101
Neutropenia Resulting from Immune Suppression of Produc- Several tests are available for detecting antineutrophil antibodies,
tion Pure white cell aplasia is a rare acquired disorder causing severe including agglutination and microagglutination, cytotoxicity, direct
selective neutropenia. The marrow is devoid or nearly devoid of neu- and indirect immunofluorescence, direct and indirect antiglobulin
89
trophils and their precursors. Ibuprofen, chlorpropamide, excessive assays, and tests involving the binding of staphylococcal protein A to
101
zinc, and various infectious and inflammatory diseases are considered immunoglobulins on the surface of cells. The agglutination tests are
possible causes of this syndrome. Differential diagnosis includes aplastic the oldest methods and depend on the propensity of immunoglobulin-
anemia, myelodysplasia, hairy cell leukemia, and neutropenia associ- coated cells to aggregate. Immunofluorescence tests utilize antihuman
ated with the large granular lymphocyte syndrome. Immunosuppressive γ-globulin tagged with a fluorescein label. These tests can be adapted
therapy with antithymocyte globulin, glucocorticoids, and cyclosporine for quantitative studies with fluorescence-activated cell sorting. Immu-
has been used in individual cases. nofluorescence and staphylococcal protein A–binding tests also can be
Chronic Idiopathic Neutropenia in Adults This is a distinct adapted for examining immunoglobulins bound to single cells, includ-
syndrome predominantly affecting young adult women ages 18 to ing marrow cells. Direct methods are used to detect the antibodies on
90
35 years; the female-to-male ratio is approximately 8:1. The medi- the patient’s neutrophils. Indirect methods are used to test the patient’s
cal history (lack of episodes of fever, gingivitis, mouth sores, or other plasma or serum against panels of normal cells. Use of paraformalde-
infections) and previous blood counts suggest the condition is acquired hyde to expose antigens and to preserve the neutrophils for multiple
in most cases. Erythrocyte, reticulocyte, and platelet counts usually are tests has been especially helpful. Appropriate controls are essential
normal. Mild leukopenia and lymphocytopenia may be present, and for proper interpretation of these studies. Measurements of apopto-
the spleen is normal or only minimally enlarged. The patients have no sis and cytokine-mediated cellular injury are done through research
chromosomal abnormalities or other evidence of myelodysplasia. 91,92 laboratories.
Marrow examinations show a spectrum of abnormalities, ranging from
normal cellularity to selective hypoplasia of the neutrophilic series. In Causes of Immune-Mediated Neutropenia
most cases, quantitative marrow studies show the ratio of immature Alloimmune Neonatal Neutropenia Newborn infants may have neu-
to mature cells is increased, suggesting loss of cells during the matu- tropenia for a variety of reasons. In some cases, the disorder results
102
93
ration process, that is, ineffective granulocytopoiesis. Antineutrophil from transplacental passage of maternal immunoglobulin (Ig) G anti-
antibodies, autoantibodies, including antinuclear or antimitochondrial bodies that bind to the infant’s neutrophil-specific antigens, usually
94
antibodies, are absent. Chronic idiopathic neutropenia in adults is the FcγRIIIb (HNA1 or CD16b) isotype inherited from the infant’s
the result of accelerated apoptosis of neutrophils and their precur- father. 103,104 Other antigens, such as NB1 glycoprotein (NB1 or CD177),
95
sors mediated via the Fas ligand or interferon-γ. The disease mech- HNA-3a(5b), HLA, and unknown antigens, also may be involved.
101
anism, that is, activation of the extracellular apoptotic pathway, is Overall, this disorder occurs in approximately 1 in 2000 neonates. The
similar to the mechanism described for patients with systemic lupus disorder usually lasts 2 to 4 months until the passively acquired anti-
erythematosus. 96 body is lost.
For most patients, the clinical course can be predicted from the Immune neonatal neutropenia may be severe or relatively mild. It
level of blood neutrophils, marrow examination, and prior history of often is not recognized until bacterial infections occur in an otherwise
fevers and infections. In general, patients with the lowest levels of blood healthy infant. The hematologic picture usually consists of severe neu-
and marrow neutrophils have the most frequent problems. Long-term tropenia with normal to increased lymphocytes and normal monocytes,
observations show, however, that some patients have very low blood erythrocytes, and platelets. Marrow cellularity is normal or increased,
neutrophil levels for long periods with few or no infections. Evolution with reduced numbers of mature neutrophils. Alloimmune neonatal
to acute leukemia or aplastic anemia generally does not occur. G-CSF neutropenia may be confused with neonatal sepsis because the latter
increases neutrophils in most patients and is a useful therapy for patients condition also causes severe neutropenia. The diagnosis of alloimmune
with recurrent fever and infections. 37,97 neutropenia usually is made using neutrophil agglutination or immu-
nofluorescence tests. Treatment should be conservative; antibiotics are
used only when necessary. Exchange transfusions to decrease antibody
DISORDERS AFFECTING NEUTROPHIL titers or neutrophil transfusions from the patient’s mother are rarely
UTILIZATION AND TURNOVER needed.
Autoimmune Neutropenia Neutrophil autoantibodies can
Mechanisms of Immune Neutropenia decrease neutrophil survival and impair neutrophil production. From a
Immune disorders primarily alter the distribution of neutrophils in the clinical perspective, however, distinguishing autoimmune neutrope-
105
blood and accelerate neutrophil turnover. Antineutrophil antibodies nia from chronic idiopathic neutropenia often is difficult. Patients
cause transfusion reactions, alloimmune neonatal neutropenia, and diagnosed with autoimmune neutropenia have one or more positive
autoimmune neutropenia. Antigen–antibody complexes, autoantibod- tests for antineutrophil antibodies. Their cytopenia is selective; other
ies, and cytokine-mediated cellular injury are possible contributors to blood cell counts are normal or near normal. Marrow morphology
neutropenia of systemic lupus erythematosus and Felty syndrome. The (Fig. 65–3), colony forming cells, and other tests, including antinu-
association of neutropenia with increased numbers of circulating large clear antibody tests, are normal. In general, therapy should be conser-
granular lymphocytes demonstrates that cellular and humoral immune vative and expectant. Intravenous γ-globulin may transiently increase
mechanisms can cause neutropenia (Chap. 94). neutrophils, but the therapy is expensive and relatively ineffective. The
Neutrophils share surface antigens with other tissues including response to glucocorticoid therapy is unpredictable. Daily or alternate-
the i-I antigens and human leukocyte antigens (HLAs). They also have day G-CSF is effective but should be reserved for patients with recurrent
some specific antigens, including NA-1, NA-2 (now recognized as iso- infections. Spontaneous remissions appear to occur much more com-
types of FcγRIII or CD16), NB-1, NC-1, and NC-9a. 98–100 A number of other monly in children than adults. 106,107

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