Results of routine heartworm antigen testing (including associated testing for Ehrlichia spp, Anaplasma spp, and Borrelia burgdorferi antibodies) were negative. Serum chemistry profile did not indicate clinically significant abnormalities. CBC revealed mild neutropenia (1.79 K/µL; reference range, 2.7-8.9 K/µL; Table).
Neutropenia is caused by decreased production, increased destruction, increased demand, and sequestration.1,2 Common differential diagnoses include infectious disease, neoplasia, bone marrow disease, drug toxicity, and uncommon genetic disease (see Causes of Neutropenia).1-4
CBC was repeated 16 days after presentation to confirm neutropenia before additional diagnostics were performed. Moderate neutropenia (0.92 K/µL) and mild thrombocytopenia were noted.4 Because the neutrophils were <1 K/µL, prophylactic antibiotic therapy was recommended to reduce the risk for sepsis pending further testing for definitive diagnosis and therapy.1,5-9 However, the pet owner chose to routinely monitor Cain’s temperature at home and have CBC rechecked on day 20, which revealed progressive neutropenia and a normal platelet count.
Cain’s owner had recently moved to wooded property; therefore, in-house tick-borne disease testing was repeated and showed a faint positive result for Ehrlichia spp antibodies. Because antibodies indicate exposure—not necessarily infection—a vector-borne disease PCR panel (including Anaplasma spp, Babesia spp, Bartonella spp, Ehrlichia spp, Mycoplasma spp, and Rickettsia spp) was submitted to a reference laboratory to determine whether an active infection was present. Pending these results, Cain was empirically treated with doxycycline (10 mg/kg PO every 24 hours for 30 days) for possible ehrlichiosis. In addition, due to the worsening neutropenia, enrofloxacin (10 mg/kg PO every 24 hours) was administered prophylactically to reduce the risk for sepsis.1,5-9 Enrofloxacin has a better gram-negative spectrum and is bacteriocidal, whereas doxycycline is bacteriostatic.
On day 31, results of the vector-borne PCR panel were positive for Mycoplasma haematoparvum and negative for Ehrlichia spp. Cain was not anemic; thus, the positive mycoplasmal PCR was suspected to be incidental, evidence of early infection, or a false-positive result. Given the negative PCR result and no clinical signs indicating ehrlichiosis (eg, fever, lethargy, petechiae, ecchymoses, lymphadenomegaly, splenomegaly), Ehrlichia spp was excluded as a cause for Cain’s leukopenia.10 A repeat CBC indicated worsening, severe neutropenia and recurrence of mild thrombocytopenia (Table). Additional diagnostic tests for causes of neutropenia were performed. Thoracic radiographs and abdominal ultrasound revealed no abnormalities. Because no causes were found for the neutropenia or thrombocytopenia, bone marrow sampling was recommended.1,2 Presence of a persistent cytopenia or multiple cytopenias increase the possibility of bone marrow disease.2 A bone marrow aspirate for cytology and a core biopsy sample were obtained with the patient under general anesthesia.
Bone marrow cytology was consistent with myeloid hyperplasia, with an increased number of immature neutrophils, indicating an appropriate response to the peripheral neutropenia. In addition, there were adequate to increased megakaryocytes consistent with an appropriate response to the intermittent peripheral thrombocytopenia. There was no evidence of inflammation, infection, or neoplasia. Based on these cytologic findings, the core biopsy was unlikely to yield additional information and was not submitted for histopathology.
Based on cytology results and negative findings for other causes, a diagnosis of immune-mediated neutropenia (IMN) was made. In humans, flow cytometry is used to detect antineutrophil antibodies and is considered the gold standard for diagnosis of IMN; however, this test is not as specific, sensitive, or readily available in veterinary medicine.2,3,11,12 IMN is an uncommon, usually idiopathic, primary condition diagnosed by exclusion of other causes of neutropenia.1,3,11 In dogs with persistent peripheral neutropenia due to IMN, the most common finding on bone marrow cytology is myeloid hyperplasia.2,3,11,12 However, some dogs may have hypoplasia, which indicates destruction of precursor cells in the bone marrow.11