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 Paraná, 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 Eritrós 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.
Background: Acute lymphoblastic leukemia (ALL) is a malignant neoplasia in which there is proliferation of lymphoid progenitor cells in the bone marrow, blood, and extramedullary sites. This disorder has a fast and progressive development; in dogs, cases of infiltration of ALL cells in the central nervous system (CNS) are uncommon and rare. Diagnosis can be achieved with the help of the clinical history and physical, radiographic, hematological, myelographic, and cerebrospinal fluid (CSF) tests in patients with or without neurological clinical signs. The present report aims to describe a case of ALL and the presence of lymphoblasts in the CSF of a dog with neurological clinical signs.Case: An 8-year-old Lhasa Apso dog was examined at the Veterinary Hospital of Universidade Federal do Paraná, Curitiba campus. At the physical examination, the animal exhibited apathy and paralysis of pelvic limbs, which progressed to tetraplegia. Abdominal palpation revealed presence of hepatosplenomegaly and absence of lymphadenomegaly. No alterations were observed in radiographs of the cervical, thoracic or lumbar spine. A complete blood count revealed presence of non-regenerative anemia (hematocrit = 22%), extreme lymphocytosis (185,229 cells/µL), lymphoblasts at a level of 72% (133,364 cells/µL), and thrombocytopenia (66,000 platelets/µL). The biochemical tests revealed increased alkaline phosphatase (859 IU/L). The levels of alanine aminotransferase, creatinine, urea, total protein, albumin, and globulin were normal. The diagnosis of ALL was achieved with the help of a myelogram. The myelogram findings included 39% of mature lymphocytes and 59% of lymphoblasts exhibiting large size, spherical shape, poorly delimited borders, with a high nucleus/cytoplasm ratio, marked cytoplasmic basophilia, and 2 to 3 evident nucleoli; metarubricytes (1%) and promyelocytes (0.6%) were also observed. The CSF contained an increased number of nucleated cells (27 cells/µL) comprising lymphocytes (43%), macrophages (33%), and segmented neutrophils (24%). Of the 11.6 lymphocytes per µL of CSF, 8.1 were lymphoblasts, which indicates infiltration of ALL cells in the CNS. The animal died one day after collection of bone barrow and CSF. Discussion: Relevant alterations observed in this case included the neurological signs caused by the infiltration of neoplastic cells in the CNS, severe leukocytosis and lymphocytosis, with large amounts of lymphoblasts in the blood and predominance of lymphoblasts in the bone marrow, which are alterations typically found in ALL. The animal also exhibited non-regenerative anemia and thrombocytopenia, which were secondary to infiltration of leukemic cells in the bone marrow. The CSF exhibited pleocytosis (27 cells/ µL), and 30% of the cells observed were lymphoblasts. Lymphoblast infiltration in the CNS of leukemic dogs is rare, and other studies have reported absence of neurological signs or neurological signs different from those observed in the present study. CSF analysis in indicated in cases of leukemia to assess leukemic cell infiltration in the CNS. In the case reported here, the plasma level of alkaline phosphatase was increased (859 IU/L) as a consequence of hepatomegaly and hepatic cholestasis. ALL is a very aggressive, proliferative neoplasia, and the resulting lymphoblasts infiltrated the CNS of the animal. In cases of ALL, performing complete blood count, myelogram, and CSF analysis is indicated whether the patients exhibit neurological signs or not.
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