Effects of medications
Many medications can cause neutropenia either by a direct toxic effect (at the level of the bone marrow or against circulating
cells) or by inducing a secondary immune-mediated disease directed against circulating neutrophils (Table 1).19 The level of cells that are targeted within the bone marrow or circulation will affect the time of onset of the cytopenia
and what blood cell lines are affected. If a neutropenic patient has a history of recent drug use, suspect the medication
as causative and discontinue it.
Table 1: Drugs That Can Cause Neutropenia in Animals*
Chemotherapeutic agents are known to cause myelosuppression, related to the suppression of cell populations with high mitotic
rates. Typically, the myelosuppression is seen five to seven days after treatment. Neutrophils are commonly affected.
Both exogenous (diethylstilbestrol, estradiol cypionate) and endogenous (Sertoli cell tumor) estrogens can cause bone marrow
suppression, perhaps because of induction of a myelopoiesis inhibitory substance from the thymus.20 The prognosis for patients may be grave since cytopenias often do not resolve with removal of the excess estrogens.
Griseofulvin may cause an idiosyncratic neutropenia in cats (particularly FIV-infected cats).21
Antithyroid medications, such as methimazole, can cause severe neutropenia. In 1.5% of cats, this occurs within the first
three months of therapy. The neutropenia typically resolves within a week of discontinuing methimazole therapy.22
In dogs, anticonvulsants, such as phenobarbital and primidone, can induce neutropenia (as well as thrombocytopenia and anemia)
as an idiosyncratic reaction. Phenobarbital can also lead to bone marrow necrosis with long-term use.23
Bone marrow disorders
Neutropenia can also be the result of disorders that affect the bone marrow. Myeloproliferative and lymphoproliferative diseases
and myelophthisis are not infrequently encountered and can result in crowding of the bone marrow space with their respective
populations and subsequent cytopenias. Bone marrow necrosis and myelofibrosis with resultant cytopenias can be caused by numerous
primary disorders (sepsis, lymphoma, drug toxicosis, or systemic lupus erythematosus), or they may be idiopathic.23
Infrequently, genetic disorders can also result in neutropenia. Cyclic stem cell proliferations are noted to occur in gray-colored
rough collies.24 The neutrophils disappear from peripheral blood at 10 to 12-day intervals, during which time dogs are clinically ill. The
syndrome results from a stem cell defect leading to abnormal responses to growth factors or accelerated cell loss through
Malabsorption of vitamin B12 in young giant schnauzers causes neutropenia that is accompanied by anemia and methylmalonic aciduria.25 This disorder responds to parenteral vitamin B12 therapy.
Border collies may present with neutropenia due to a rare disease that causes failure of segmented neutrophils to enter peripheral
Chediak-Higashi syndrome, a form of albinism seen in cats as well as other species, may have a concurrent neutropenia.
Signalment and clinical signs
No breed, sex, or size predisposition has been identified for immune-mediated neutropenia. However, dogs younger than 4 years
old may be 4.1 times as likely to develop idiopathic neutropenia as are dogs older than 4 years.16