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immune-mediated neutropenia (part 1)

Joshua W. Tumulty, DVM, DACVIM (Int. Med.)
Chairman, Dept of Internal Medicine
Long Island Veterinary Specialists




neutrophils are a part of the granulocytic because of
cell line and play an essential role in initiating Increased margination or egress of neu-
an immune response to invading pathogens, trophils from the circulating pool to the
such as bacteria, and releasing chemotactic marginated pool as may occur with in-
substances that attract other inflammatory fection, immune-mediated disorders, or
cells, such as monocytes. Neutropenia (< 3,000 hypersplenism
neutrophils/l in dogs, < 2,500 neutrophils/l Decreased production resulting from
in cats) as a solitary laboratory fnding is often bone marrow injury, such as that caused
not associated with clinical signs and may be by certain drugs, or infltration as in my-
detected on routine screening of otherwise elophthisis (normal hemopoietic tissue noted. If the infectious process is overwhelm-
apparently healthy patients. Alternatively, is replaced with fbrous tissue or a non- ing, increased destruction may exceed bone
neutropenic dogs may present with a fever or hemopoietic tissue such as carcinoma), marrow production. Some infections, such as
lethargy or other signs associated with infec- myeloproliferative disorders, and lympho- canine monocytotropic ehrlichiosis, impair
tion. Prompt recognition and treatment are proliferative disorders bone marrow proliferation. Neutropenia may
vital because if the neutropenia is not resolved, Increased consumption or destruction also be associated with systemic mycosis
infections may be persistent or recurrent and of neutrophils as in immune-mediated (histoplasmosis, cryptococcosis) if myelo-
may result in death. destruction or severe infection in which phthisis occurs and results in subsequent
Immune-mediated neutropenia is a primary use or destruction is in excess of bone cytopenias (Figure 1).
disorder or may occur secondary to infection, marrow production and release of neu- In dogs, the most common infection con-
neoplasia, or the effects of certain drugs. It trophils. sistently associated with neutropenia is par-
results when antibodies directed against neu- These causes of neutropenia are not mutu- vovirus. In both dogs and cats, parvovirus
trophil surface antigens or potentially against ally exclusive, and multiple mechanisms are targets tissues with high mitotic rates such
growth regulators of granulopoiesis develop. It frequently concurrent. as the bone marrow, leading to cytotoxic he-
can occur concurrently with other immune-me- Immune-mediated neutropenia represents matopoietic cell death as well as ineffective
diated diseases, such the least common hematopoiesis. Parvovirus infection will also
as rheumatoid arthri- cause of neutropenia lead to increased neutrophil margination and
tis or systemic lupus Immune-mediated and results primar- consumption associated with gastrointestinal
erythematosis in dogs neutropenia is a primary ily from increased damage and endotoxemia.
and people. Immune- disorder or may occur destruction of neutro- In cats, feline leukemia virus (FeLV) and
mediated neutropenia phils when they be- feline immunodeficiency virus (FIV) infec-
is a well-recognized secondary to infection, come coated with anti- tions are the most common infectious causes
cause of neutropenia neoplasia, or the effects of neutrophil antibodies. of neutropenia. FeLV infection causes the
in people, primarily af- certain drugs. The spleen also se- destruction of hematopoietic stem cells and
fecting infants. Much questers antibody- ineffective maturation of neutrophils associ-
of the available infor- coated blood cells, so
mation about immune-mediated neutropenia increased margination may concurrently be Continued on Page 13 ➤
in animals is extrapolated from the disease present (Felty syndrome: neu-
in people. tropenia, rheumatoid arthritis,
Immune-mediated neutropenia is a rela- and splenomegaly).
tively uncommon cause of neutropenia in cats
and dogs, and recognizing it is challenging. It Differential Diagnoses
can only be identifed by understanding the For Neutropenia
pathophysiology of neutropenia in general and Neutropenia can occur for a va-
ruling out its differential diagnoses. This ar- riety of reasons including infec-
ticle will review the pathophysiology of neutro- tions, drug reactions, and bone
penia, and the differentials that accompany the marrow and genetic diseases.
neutropenic patient. An accompanied article
will subsequently review the diagnostic and Infections
therapeutic approach for immune-mediated Overall, infections with bac-
neutropenia. teria, viruses, and fungi are
the most common causes of
Pathophysiology Of Neutropenia decreased neutrophils. In the
Several mechanisms of neutropenia must be case of endotoxemia, sepsis,
considered before diagnosing immune-me- or localized infections, in- Figure 1 Bone marrow cytology demonstrating canine Leishmaniasis
diated neutropenia. Neutropenia can occur creased margination may be


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