Cytopenia. Bone marrow aspiration or core biopsy is a useful diagnostic tool. It is indicated if there are concurrent cytopenias that cannot be explained by immune-mediated mechanisms or if these cytopenias lack a regenerative response. Bone marrow may show a neoplastic population of cells such as leukemia. Hypoplastic marrow would lend evidence to a drug-induced cytopenia, canine monocytotropic ehrlichiosis, immune-mediated neutropenia due to antibodies directed at bone marrow, or an idiopathic cause of neutropenia. Plasmacytosis may point toward Ehrlichia canis infections.²⁷

In the case of immune-mediated neutropenia, bone marrow aspiration typically reveals hypercellular bone marrow, though hypoplasia can also be seen.⁵ Myeloid hyperplasia with a lack of mature neutrophils in the marrow but lots of bands would suggest peripheral destruction of the neutrophils as opposed to decreased production.

DIAGNOSIS

To definitively diagnose immune-mediated neutropenia, antineutrophil antibodies must be demonstrated. However, no validated canine and feline assays for antineutrophil antibodies exist.^28,29 The difficulty of developing a reliable test in veterinary medicine is related to the inherent fragility of neutrophils and their propensity to degranulate and aggregate in vitro. Many granulocyte antibodies are likely involved. In people, multiple tests are available to detect antibodies against the five different neutrophil surface antigens that are targeted in immune-mediated neutropenia.

Additionally, there are tests for people for antibodies directed against less-specific surface antigens that may be found on multiple cell types.²⁸ The presence of antibodies against these less-specific antigens may lead to concurrent immune-mediated diseases, such as rheumatoid arthritis, immune-mediated thrombocytopenia, or immune-mediated hemolytic anemia. In veterinary medicine, IgG and complement 3 were associated with bone marrow neutrophil elements in two dogs with suspected immune-mediated neutropenia.² More recently, IgG associated with circulating neutrophils in five of six dogs with immune-mediated neutropenia was demonstrated by using flow cytometry.³⁰ However, it was unknown if the targets were neutrophil-specific, a shared antigen, or adsorbed surface antigen.^11,30

Exclusion of other causes

Lacking tests to prove an immune-mediated cause, the diagnosis is determined by excluding other causes and by receiving a positive response to immunosuppression. Concurrent detection of other immune-mediated diseases, such as immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, steroid-responsive meningitis, immune-mediated non-erosive arthritis, panniculitis, or vasculitis, also gives support to the neutropenia being immune-mediated. ^3,4,8,14

TREATMENT

After a short course of antibiotic therapy, treating immune-mediated neutropenia requires immunosuppressive drug regimens.

Antibiotics

Typically, a two- to three-day course of bactericidal antibiotics (beta-lactams, aminoglycosides, fluoroquinolones, and trimethoprim-sulfonamides) is given before instituting immunosuppression. A bacteriostatic antibiotic would require a functional neutrophil population, which is lacking in these patients. A typical regimen might be ampicillin combined with an aminoglycoside. Successful treatment of a concurrent infectious process may improve clinical signs and resolve the toxic change but will not resolve the neutropenia.

Prednisone

To increase the neutrophil numbers, initiate prednisone therapy (2 to 4 mg/kg once a day). Admitting the patient to the hospital for the first few days of therapy to monitor for signs of infection (monitor rectal temperature every four to six hours) is advisable. Neutrophil counts should begin to rise within a few days of instituting immunosuppressive therapy, but it may take up to three weeks to reach acceptable counts (> 1,500/μl in dogs and > 1,000/μl in cats).⁵ Provided the counts remain acceptable, taper immunosuppressive therapy by reducing the dosage 25% every two to four weeks. As with other immune-mediated diseases, lifelong therapy may be required, and the lowest effective dose should be administered every other day.