October 02, 2017

Promising New Treatment for Ehrlichiosis-Associated Pancytopenia

Treatment with a human granulocyte-colony stimulating factor analog can markedly improve the clinical course of chronic canine ehrlichiosis.
By JoAnna Pendergrass, DVM
Canine monocytic ehrlichiosis (CME) is caused by the rickettsial bacterium Ehrlichia canis, which is transmitted to the host by the tick Rhipicephalus sanguineus. Distributed worldwide and affecting multiple body systems, CME has 3 clinical phases—acute, subclinical, and chronic.

Bone marrow aplasia is a common and fatal sequela of chronic CME. It can cause bleeding and superinfections due to thrombocytopenia and neutropenia, respectively, making disease management challenging. Despite these serious complications, which can lead to a poor prognosis for patients with CME, it remains unclear why myelosuppression occurs with CME; possible reasons include immune dysfunction and E. canis strain.

A report recently published in Topics in Companion Animal Medicine described the case of a dog with chronic CME-associated nonregenerative pancytopenia that made a remarkable recovery after treatment with high-dose filgrastim.

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Case Presentation
An 8-year-old male mixed-breed dog weighing about 6 kg “presented with a 1-month history of hyporexia, adynamia, and a weight loss of approximately 1 kg,” the report’s authors wrote. Physical examination findings, including tachycardia, abdominal petechiae, and lethargy, indicated poor condition.

Complete blood count results revealed severe leukocytopenia, thrombocytopenia, and anemia. No blood chemistry abnormalities were present. A direct immunofluorescence assay was positive for E. canis. The dog tested negative for Anaplasma sp and Babesia spp.

Treatment
Initial treatment involved doxycycline and imidocarb diproprionate to kill E. canis. The anemia was treated with erythropoietin, iron, and folate. The authors noted that off-label human erythropoietin use is common for treating canine diseases; however, it has limited usefulness in chronic conditions because of anti-erythropoietin antibody development. The iron and folate corrected the iron deficiency that can occur with CME-associated bone marrow aplasia.

Following initial treatment, the dog improved slightly because of increased erythrocyte production, but leukocyte and platelet deficiencies remained. Petechiae, epistaxis, and gingival bleeding worsened.

Subsequently, the dog received a short course of high-dose filgrastim (50 µg/kg SC q48h) and prednisolone. Filgrastim can reportedly treat canine neutropenia due to toxins and bone marrow transplantation. For CME, prolonged therapeutic filgastrim doses have shown limited clinical success, justifying the short course and high dose described in this case report.

The prednisolone treated the dog’s thrombocytopenia, which, in CME, can result from splenic sequestration and platelet destruction. Prednisolone use can be controversial due to the risk of exacerbating immunosuppression. In this case, though, the dog’s worsening bleeding problems justified prednisolone treatment.

After filgrastim and prednisolone treatment, the dog’s adynamia initially worsened, potentially due to bone pain associated with high-dose filgrastim; the hyporexia also worsened. Two weeks post-filgrastim, the dog had fewer bleeding problems, more energy, and a better appetite. Neutrophil and platelet counts steadily improved, with the dog making a full recovery 2 months after diagnosis.

Implications
Based on this dog’s full recovery, the authors suggested that a treatment regimen including high-dose filgrastim is a reasonable alternative for treating chronic CME-associated pancytopenia.

Because filgrastim and erythropoietin treatment for CME would be considered off-label usage, the authors advised veterinarians to “always report adverse effects and therapeutic failures to the veterinary pharmacovigilance program when using off-label medications.”

 
Dr. Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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