Dogs may be asymptomatic or may be presented for nonspecific clinical signs. How long dogs or cats might be neutropenic before showing clinical signs is unknown, but the duration from the onset of illness to the time of referral ranged from three to 180 days (median = 46 days) in one retrospective case series.⁵ Commonly reported clinical signs include lethargy, lameness (possibly shifting), and anorexia.¹⁶ Less commonly reported signs include diarrhea, vomiting, and hypersalivation.^2,3,11

History taking and physical examination

Given that infections and drug administration are the most common causes of neutropenia, history taking and physical examinations need to be directed at gathering information relevant to these areas.

Physical examinations need to be directed at detecting any nidus of infection. Careful auscultation for murmurs (endocarditis), abdominal palpation, spinal palpation (discospondylitis), and palpation of the lymph nodes are vital.

Persistent fever is the most frequently reported physical examination finding in dogs and cats with immune-mediated neutropenia.⁶ In case reports, joint effusion, conjunctivitis, facial edema, oral ulcerations, epistaxis, pyoderma, abscessation of a digit with local lymphadenomegaly, abdominal pain, mucoid vaginal discharge, and scrotal inflammation have all been reported.^2,3,5,11

Complete blood count

On a complete blood cell count (CBC), dogs with immune-mediated neutropenia have a lower neutrophil count than do dogs with neutropenia attributed to other causes.⁶ Severe neutropenia (< 500/μl) with a lack of toxic change is common,¹⁴ although reports in the literature are limited. Similarly, some reports of immune-mediated neutropenia in cats reveal that the cats commonly have a marked lymphocytosis and mild thrombocytopenia.¹⁴ Toxic change of neutrophils strongly indicates concurrent secondary infection and should resolve with appropriate antibiotic therapy.

Concurrent anemia, which can be immune-mediated or from chronic inflammation or bone marrow disease, may be noted. Thrombocytopenia may also be noted, with immune-mediated thrombocytopenia or bone marrow disease being the most likely causes. Multiple cytopenias increase the likelihood of bone marrow disease.

Blood smear cytology may show clumping of neutrophils.³ It has been proposed that a concurrent monocytosis may compensate for the lack of neutrophils; this situation is seen in people. Concurrent lymphocytosis may be related to chronic antigenic stimulation and may lead to hypergammaglobulinemia.

Additional diagnostic testing

Ultimately, the diagnostic approach to a neutropenic dog or cat depends on whether the patient is symptomatic and how severe the neutropenia is.

Febrile patients. If the patient is febrile, look for a septic focus such as a pulmonary, hepatic, or splenic infection or abscess. Use radiography and ultrasonography, and obtain blood, urine, joint fluid, and cerebrospinal fluid samples for bacterial culture.

If the results of these tests are negative, consider using a technetium-99m-labeled neutrophil scan to detect neutrophil accumulation at a focus of infection. Serologic or polymerase chain reaction tests are also indicated to rule out infectious disorders such as ehrlichiosis in dogs and FeLV and FIV infections in cats.

Anemic patients. With the presence of anemia, especially if it is marked, Coombs tests are indicated. An antiplatelet antibody test in dogs with concurrent thrombocytopenia may be of interest. Evidence of concurrent immune-mediated blood cell destruction supports a diagnosis of immune-mediated neutropenia. Similarly, positive antinuclear antibody or rheumatoid factor test results may lend evidence of concurrent immune-mediated disease. False positive results are common if these tests are run indiscriminately (e.g. testing for rheumatoid factor in a dog without evidence of erosive polyarthritis).¹⁴ Similarly, restrict antinuclear antibody testing to those patients in which concurrent nonerosive polyarthritis is present or suspected.