Pancytopenia in a Dog Induced by Concomitant Use of Myelotoxic Drugs

Abstract

Background: The indiscriminate use of drugs is an issue in Veterinary Medicine, as it has serious consequences for the animals. Many drugs are myelotoxic and cause a decrease in the production of blood cells, which may be irreversible in some cases. The present work reports a case of pancytopenia induced by the concomitant use of myelotoxic drugs (estrogen, metamizole and phenobarbital) in a dog and describes findings on myelotoxicity, hematological alterations and treatment success. Case: A 7-year-old Lhasa Apso bitch was referred to the Veterinary Hospital of Federal University of Parana, Curitiba campus, with hematuria and a history of treatment with phenobarbital [2 mg/kg twice a day (bis in die, BID)], metamizole [25 mg/kg three times a day (ter in die, TID)], and use of estrogen hormone (estradiol cypionate). At physical examination, the animal was normohydrated and exhibited normal palpable lymph nodes, pale mucous membranes, galactorrhea, and a body temperature of 36°C. A complete blood count including reticulocyte count and a total plasma protein (TPP) exam were requested. The results revealed pancytopenia (18% hematocrit, 1,400 total leucocytes/µL, and 22,000 reticulocytes/µL). An abdominal ultrasound exam did not detect any relevant alterations. In view of the results obtained, medullary aplasia was suspected. A bone marrow aspiration was performed. A myelogram revealed a decrease in cellularity (erythrocytic and granulocytic hypoplasia), with presence of rare erythroid and granulocytic precursors. The diagnosis was medullary aplasia. The animal was treated, and the evolution of the hematological alterations was monitored. The treatment consisted of administration of erythropoietin (100UI/kg subcutaneously every 48 h), prednisone (2 mg/kg BID), Leucogen (3 mg/kg BID), interferon (0.2 IU/kg BID) and Eritros Dog Tabs [1 tablet once a day (semel in die, SID)]. After five days of treatment, the patient’s clinical picture improved (30% hematocrit, 5,300 total leukocytes/µL, 84,000 platelets/µL, and 195,000 reticulocytes/µL), and the hematological alterations were resolved after 25 days of treatment (43% hematocrit, 5,100 total leukocytes/µL, and 333,000 platelets/µL). The bitch was discharged after 89 days of treatment. Discussion: The hematological alterations found in the patient were consistent with pancytopenia, and the myelogram allowed the establishment of a diagnosis of medullary aplasia. There are various causes of pancytopenia in dogs; in this case, it was caused by medications, as the drugs administered to the patient (estrogens, metamizole, and phenobarbital) are myelotoxic. Canine bone marrow is susceptible to suppression by estrogens, which can induce medullary aplasia even with a single dose. No reports on hematological alterations caused by dipyrone (metamizole) in dogs were found; however, in humans, development of aplastic anemia, agranulocytosis, nephrotoxicity, and allergic reactions have been attributed to the use of this drug. Phenobarbital can cause adverse reactions that lead to anemia, leukopenia, and thrombocytopenia. Evaluating the bone marrow of animals with pancytopenia is important because this procedure allows the establishment of a diagnosis that may prompt treatment while hematopoietic precursors are still present in the bone marrow. In this case, a treatment using hematopoietic stimulants was employed owing to the presence of erythrocytic and myelocytic precursors in the patient’s bone marrow. The treatment instituted was efficacious, as only five days of therapy already improved the hematological condition of the patient, who was discharged after 89 days of treatment.