Systemic toxicosis associated with azathioprine administration in domestic cats.

Five cats were treated with an azathioprine suspension (2.2 mg/kg of body weight on alternate days) and 2 cats were given vehicle (controls) for 9 weeks. Complete blood and platelet counts and serum biochemistry variables were monitored weekly. Bone marrow aspirates were evaluated every 3 weeks, and core bone marrow biopsy was performed at the end of the study. Profound neutropenia (less than 600 cells/microliters) was observed in all treated cats, and 1 cat developed pancytopenia. Treatment was discontinued if the WBC count was less than 3,000 cells/microliters. Four weeks after discontinuation of azathioprine, 1 treated cat again was given azathioprine at a lower dosage (1.1 mg of azathioprine/kg on alternate days) and neutropenia recurred within 2 weeks. During treatment, 3 cats developed thrombocytosis, and 2 developed thrombocytopenia. In 4 of 5 cats, neutropenia and thrombocytopenia resolved when azathioprine was discontinued. Bone marrow cytologic examination during treatment revealed reduction of the neutrophil line, with relative increase in monocytes. Core bone marrow biopsy at the completion of the study revealed hypocellular marrow with marked decrease in the myeloid series in cats given azathioprine. One of the cats that was treated with azathioprine had a hypercellular marrow with increased numbers of mature granulocytes and precursors; however, azathioprine had been discontinued 3 weeks prior to biopsy. Alterations in serum biochemical variables were not associated with azathioprine. Two cats that were treated with azathioprine developed respiratory tract infections, and 1 of them was euthanatized during the study.     

Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus‐negative cat

A 10‐year‐old castrated Domestic Short‐Haired cat was presented to a primary care veterinarian for a wellness examination and laboratory examination for monitoring of diabetes mellitus. The CBC revealed marked thrombocytosis, leukopenia and macrocytic, normochromic anemia. The cat tested negative for FeLV and feline immunodeficiency virus, but was positive for Mycoplasma haemominutum by PCR. Hematologic abnormalities were not responsive to therapy, so a repeat CBC and a bone marrow aspiration for cytology were performed. Additional blood smear findings included anisocytosis with megaloblastic erythroid precursors, large platelets, eosinophilic myelocytes and metamyelocytes, and rare unidentified blasts. The bone marrow smear was highly cellular, and the cytologic pattern was consistent with myelodysplastic syndrome with an erythroid predominance. At that time, 15% blasts were present. The cat was treated with a vitamin K₂ analog, doxycycline, and prednisolone, but without a clinical response. Within 3 months, euthanasia was elected due to declining quality of life, and a necropsy was performed. Postmortem bone marrow smears were highly cellular and dominated by monomorphic blasts of unknown line of origin (52%), persistent marked erythroid and megakaryocytic dysplasia, and ineffective erythropoiesis and granulopoiesis. Immunohistochemical, immunocytochemical, and cytochemical stains resulted in a diagnosis of acute myeloid leukemia of unclassified type. Additional histologic findings included mixed hepatitis with trematode infestation and lymphoplasmacytic interstitial nephritis with fibrosis. The marked thrombocytosis with myelodysplastic syndrome and the FeLV‐negative status of this cat were unusual. The difficulty in classifying the myelodysplasia and subsequent leukemia highlights a need for further reporting and characterization of these types of disease.     

Blood smear from a cat: features to "dys"cover

A 4-year-old, spayed female, domestic shorthair cat was presented for lethargy, nonregenerative anemia, and inappetence. Results of a CBC included macrocytic, normochromic, nonregenerative anemia and a glucocorticoid-associated leukogram. On blood smear examination, neutrophils had abnormal features including hyposegmentation and a diffuse chromatin pattern with nuclear filament formation and nuclear blebbing. Microscopic examination of a roll preparation of bone marrow revealed hypolobulated megakaryocytes with asynchronous maturation of nuclei. The granulocytic to erythrocyte (G:E) ratio was 76. Segmented neutrophils had asynchronous maturation and dysplastic features. The entire erythroid lineage was markedly decreased for the degree of anemia and rare dysplastic features were noted in erythroid precursor cells. The interpretation of bone marrow findings was erythroid hypoplasia, megakaryocytic dysplasia, and granulocytic hyperplasia with dysplasia. Histopathologic examination of a bone marrow core sample also revealed myeloid hyperplasia and erythroid hypoplasia. The result of a direct immunofluorescence assay for FeLV performed on the bone marrow roll preparation was positive. A diagnosis of dysmyelopoiesis associated with FeLV infection was made. This case was unique in that the dysplastic changes occurred in cell lines that did not have associated cytopenias. The dysmyelopoiesis most closely resembled myelodysplastic syndrome with refractory cytopenia (MDS-RC); however, secondary dysmyelopoiesis could not be ruled out.     

Presumptive fenbendazole toxicosis in North American porcupines

CASE DESCRIPTION: 4 North American porcupines were evaluated because of diarrhea or neutropenia (or both) that developed after treatment with fenbendazole for intestinal parasites. CLINICAL FINDINGS: Complete blood cell count abnormalities included severe neutropenia in all affected porcupines and mild anemia in some of them. In 2 porcupines, postmortem findings included bone marrow hypoplasia and intestinal crypt cell necrosis. TREATMENT AND OUTCOME: Affected porcupines received supportive care including fluid supplementation and broad-spectrum antimicrobials. The 2 surviving animals recovered after 9 to 33 days of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Fenbendazole is an anthelminthic that may be used in an extralabel manner for the treatment of intestinal parasitism in wildlife species. The drug inhibits mitosis and can affect rapidly dividing cell lines, such as those in the bone marrow and intestinal crypt mucosa. Fenbendazole may not be an appropriate anthelminthic choice in North American porcupines.     

Prospective Hematologic and Clinicopathologic Study of Asymptomatic Cats With Naturally Acquired Feline Immunodeficiency Virus Infection

Prospective studies were performed over a 28- to 77-month period (median, 66 months) on 5 cats with naturally acquired feline immunodeficiency virus (FIV) infection in an attempt to correlate hematologic and Clinicopathologic changes with the emergence of clinical disease. On presentation, all cats were asymptomatic; free of opportunistic infections; and had normal complete blood counts, bone marrow morphologies, marrow progenitor frequencies, and progenitor in vitro growth characteristics. During study, 2 cats remained healthy, 2 cats showed mild clinical signs, and 1 cat developed a malignant neoplasm (ie, bronchiolar-alveolar adenocarcinoma). Although persistent hematologic abnormalities were not observed, intermittent peripheral leukopenias were common. In 3 of 5 FlV-seropositive cats, lymphopenia (< 1,500 lymphs/μL; normal reference range, 1,500 to 7,000 lymphs/μL) was a frequent finding and the absolute lymphocyte counts had a tendency to progressively decline. One of the other 2 cats had consistently low to low-normal absolute neutrophil counts (1,300 to 4,800 segs/μL; mean, 2,730 segs/μL; normal reference range, 2,500 to 12,500 segs/μL), and the remaining cat had consistently normal leukograms, except for a transient period (ie, 11 months) of benign lymphocytosis (7,200 to 13,430 lymphs/μL) early in the study. Periodic examinations of bone marrow aspirates revealed normal to slightly depressed myeloid-to-erythroid ratios with normal cellular morphology and maturation. Bone marrow abnormalities observed late in the study included mild dysmor-phic changes (ie, megaloblastic features) in 2 cats, and a significant decrease (60% of controls, P < .001) in the frequencies of burst-forming units erythroid (BFU-E) in marrow cultures of FIV-seropositive cats compared with uninfected control cats. Serum biochemical profiles were unremarkable throughout the study, with the exception of hyperglobulinemia (ie, polyclonal gammopathy) in 2 of 5 cats. Peripheral blood and bone marrow findings were of no apparent prognostic value. These results confirm the long latency between natural FIV infection and the development of life-threatening clinical disease. Chronic FIV infection, like infection with human immunodeficiency virus, can be associated with derangements in peripheral blood cell counts, as well as pertubations in marrow cell morphologies and hematopoietic progenitor frequencies before the terminal symptomatic stages of retroviral disease, when persistent cytopenias are prominent.     

Occipitoatlantoaxial malformation with atlantoaxial subluxation in a cat

Occipitoatlantoaxial malformation and atlantoaxial subluxation was diagnosed in a three-year-old castrated male domestic shorthair cat. Clinical signs included ataxia, postural reaction deficits, abnormal spinal reflexes, and behaviour changes. Radiographic examination revealed malformation and hypoplasia of the occipital condyles, hypoplasia of the dens, and atlantoaxial subluxation. Electroencephalographic (EEG) findings included high voltage slow activity and sharp waves with superimposed low voltage fast activity in the occipital leads and sinusoidal beta waves in the frontal leads. Basilar artery compression as a result of atlantoaxial instability is suspected to have caused the behavioural changes and EEG abnormalities in this patient. The cat was treated by stabilisation of the atlantoaxial subluxation by ventral cross pin fixation, odontectomy, and arthrodesis of the atlantoaxial articulation. The patient responded well to treatment and was neurologically normal 18 months after surgery.     

Erythrocyte dysplasia in peripheral blood smears from 5 thrombocytopenic dogs treated with vincristine sulfate

Secondary dyserythropoiesis has been associated with vincristine administration in dogs. Evaluation of bone marrow aspirates for the presence of morphologic abnormalities in the erythroid lineage aids in the diagnosis. However, morphologic features of circulating erythroid precursors in these cases have not been described previously. The purpose of this report was to describe the cytologic features of dyserythropoiesis in peripheral blood and also bone marrow smears in a case series of dogs with immune‐mediated thrombocytopenia (IMT) treated with vincristine sulfate. Nineteen dogs receiving vincristine for treatment of IMT were identified by retrospectively searching a computerized medical record system. There were 5 dogs that had dysplastic erythroid precursors in peripheral blood smears within 7 days of vincristine treatment. Two of those 5 dogs also had evidence for erythrodysplasia in modified Wright's‐stained bone marrow smears obtained postvincristine administration. Morphologic changes included bizarre or inappropriate mitotic figures, abnormal nuclear configurations (fragmentation, elongation, indentation, and binucleation), atypical nuclear remnants (Howell‐Jolly bodies), or nuclear and cytoplasmic asynchrony within the erythroid precursors. A brief review of the literature with discussion of the etiologies for dyserythropoiesis is provided. The dyserythropoiesis was clinically insignificant in all 5 cases and resolved. However, pathologists and clinicians should be aware of these potential findings to prevent misdiagnosis of other conditions.     

Chronic Idiopathic Neutropenia in a Cat

Persistent neutropenia (0-0.6 X 10(9) neutrophils/l) was documented during a 10-month period in a 4-year-old spayed female domestic shorthair cat that was presented for anorexia and depression. Salient abnormalities detected on physical examination were fever (40.3 degrees C), dehydration, and gingivitis. The cat was neutropenic (0.5 X 10(9) neutrophils/l) and enzyme-linked immunosorbent assay (ELISA) test for feline leukemia virus was negative. A bone marrow aspirate showed decreased numbers of mature granulocytic cells. In vitro bone marrow cultures for colony-forming units-granulocyte/macrophage (CFU-GM) were performed comparing bone marrow from the patient with that of a normal cat. The patient had fewer CFU-GM than the control. The number of CFU-GM increased when bone marrow mononuclear cells were cultured in the presence of 10(-5) and 10(-6) mol/l of hydrocortisone, but the cat did not respond to oral prednisolone therapy. The pathogenesis of the neutropenia in this cat remains obscure, but resembles the chronic idiopathic neutropenia syndrome of man.     

Bone marrow hypoplasia in a feminized dog with an interstitial cell tumor.

Bone marrow hypoplasia and feminization developed in a 10-year-old male German Shepherd Dog with interstitial cell tumor. Clinical abnormalities included pyrexia, pale mucous membranes, signs of abdominal pain, large left testis, atrophied right testis, and feminization. Abnormal laboratory findings included pancytopenia, bacteremia, bacteriuria, and pyuria. Results of cytologic examination of a bone marrow aspirate were consistent with aplastic anemia. Serum estradiol concentration was high, and serum testosterone concentration was low, compared with normal values for male dogs. The left testicular mass was identified as an interstitial cell tumor. Other causes of the aplastic anemia or feminization were not found.     

Hemophagocytic syndrome in a cat with multiple myeloma

An 11‐year‐old, castrated male, Domestic Medium Hair cat was presented to the University of Florida Small Animal Hospital with a 2‐week history of upper respiratory infection and increased serum globulins, as reported by the referring veterinarian. Physical examination was unremarkable other than melanosis of the left iris, with no evidence of ocular, nasal, or respiratory disease. Laboratory abnormalities included moderate nonregenerative anemia, mild leukopenia, mild hyperfibrinogenemia, severe hyperglobulinemia, mild hypoalbuminemia, and hypocholesterolemia. Abdominal radiographs and ultrasonographic examination revealed mild splenomegaly with no other abnormalities. Thoracic radiographs revealed no abnormalities. Cytologic evaluation of fine‐needle aspirates from the spleen, liver, and bone marrow revealed numerous plasma cells and many vacuolated macrophages exhibiting marked phagocytosis of mature erythrocytes and platelets, occasionally metarubricytes and leukocytes, and rarely plasma cells. The cytologic interpretation was multiple myeloma and associated hemophagocytic syndrome (HPS). Serum protein electrophoresis revealed a monoclonal gammopathy, providing further evidence for a multiple myeloma. To the authors' knowledge, this is the first report of HPS secondary to neoplasia in a cat.     

Dysmyelopoiesis in the cat: a hematological disorder resembling refractory anemia with excess blasts in man.

Clinical and pathological findings in three cats affected with a myelodysplastic disorder are presented. This hematological disorder resembles that of refractory anemia with excess of blasts as seen in man. The hematological profile in man is one of peripheral cytopenia in one or all of the marrow cell lines which occurs despite a normal to hypercellular bone marrow. Quantitatively, the marrow has a preponderance of blasts (up to 20%). Qualitative abnormalities consist of dysthrombopoiesis and/or dyserythropoiesis and/or dysgranulopoiesis. Myelodysplastic disorders in the cat are a form of marrow failure often associated with infection with feline leukemia virus. The use of the term refractory anemia with excess of blasts appears to be applicable to the cat and should be considered in evaluating dysplastic disorders of the feline bone marrow.     

Diagnostic use of cytologic examination of bone marrow from dogs with thrombocytopenia: 58 cases (1994-2004)

OBJECTIVE: To determine the diagnostic use of cytologic examination of bone marrow from dogs with thrombocytopenia. DESIGN: Retrospective case series. ANIMALS: 58 dogs with thrombocytopenia. PROCEDURES: Medical records were searched and reviewed for dogs with thrombocytopenia. Dogs that had thrombocytopenia and cytologic examination of bone marrow were included in the study. Dogs with other hematologic abnormalities, with a previous diagnosis of hematopoietic neoplasia, or that had previous treatment with cytotoxic drugs were excluded. Bone marrow cytologic findings were reviewed. Results were compared between dogs with severe thrombocytopenia (< 20,000 platelets/microL) and dogs with mild to moderate thrombocytopenia (20,000 to 200,000 platelets/microL). RESULTS: 58 dogs met the inclusion criteria. Of 55 dogs with diagnostic bone marrow aspirates, 36 had severe thrombocytopenia. Cytologic evaluation of bone marrow did not reveal substantial nonmegakaryocytic bone marrow abnormalities or result in a definitive diagnosis in any of these dogs. Nineteen dogs with mild to moderate thrombocytopenia had diagnostic bone marrow aspirates. Bone marrow cytologic findings revealed nonmegakaryocytic abnormalities in 4 of these dogs. Significantly fewer dogs with severe thrombocytopenia had abnormalities identified on cytologic examination of bone marrow, compared with dogs with mild to moderate thrombocytopenia. CONCLUSIONS AND CLINICAL RELEVANCE: Cytologic examination of bone marrow is unlikely to provide specific diagnostic or prognostic information in dogs with severe thrombocytopenia.     

Bone marrow mastocytosis in dogs with myelosuppressive monocytic ehrlichiosis (Ehrlichia canis): a retrospective study

BACKGROUND: Bone marrow mastocytosis has been reported rarely in naturally occurring canine monocytic ehrlichiosis (CME). OBJECTIVES: The aims of the present study were to estimate the prevalence and magnitude of bone marrow mastocytosis in a case series of dogs with natural CME and to assess the association, if any, between mastocytosis and the clinical severity of the disease. METHODS: Seventy-six dogs with confirmed CME (Ehrlichia canis) were included in the study. Affected dogs were allocated into group A (n = 51) without bone marrow hypoplasia and group B (n = 25) with bone marrow hypoplasia. Twenty clinically healthy Beagles not previously exposed to E canis served as controls (group C). The main inclusion criteria for group A were documentation of normocellular to hypercellular bone marrow and complete clinical cure following a 4-week treatment with doxycycline, while those for group B were bone marrow hypoplasia and lack of response to doxycycline. Bone marrow aspirate smears from all 96 dogs were Giemsa-stained and examined for the presence of mast cells, which were calculated as a percentage of 1,000 nucleated cells (NCs). The prevalence of mastocytosis was compared among the 3 groups by the Pearson's chi-square test. RESULTS: Bone marrow mastocytosis (>0.1% of NCs) was found in 5 (20%) dogs in group B (range, 0.5-2.5% of NCs; median, 1% of NCs). One dog in each of groups A and C had 0.1% mast cells in the marrow. The prevalence of bone marrow mastocytosis in dogs in group B was significantly higher (P = .004) than in groups A and C. CONCLUSION: Bone marrow mastocytosis can be seen in a substantial number of dogs with E canis-induced myelosuppression.     

Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks

Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.     

Persistent nonregenerative anemia in a 4-year-old cat

A 4-year-old male neutered domestic shorthair cat was presented to The Ohio State University College of Veterinary Medicine for a 2-month history of severe weight loss, lethargy, anemia, and bilaterally hyperechoic kidneys with loss of corticomedullary distinction as reported by the referring veterinarian. Relevant initial laboratory results included severe non-regenerative normocytic hypochromic anemia, increased blood urea nitrogen, minimally concentrated urine, proteinuria, and an increased urine protein:creatinine ratio. Cytologic evaluation of a bone marrow aspirate revealed a markedly hypocellular marrow with abundant mucinous material. Gelatinous marrow transformation (GMT) was confirmed histologically by the presence of mucinous material in the bone marrow that stained positive for Alcian blue but negative for periodic acid-Schiff. The cat died despite repeated blood transfusions and supportive care. Gelatinous marrow transformation, immune complex-mediated membranoproliferative glomerulonephritis, and gastrointestinal hemorrhage were observed on autopsy and histology. It is likely that the development of GMT was secondary to chronic kidney disease (CKD) and that CKD, GMT, and gastrointestinal hemorrhage contributed to the cat's non-regenerative anemia.     

Presumptive precursor-targeted immune-mediated anemia concurrent with gastrointestinal lymphoma in a cat

A 10-year-old spayed female mixed-breed cat presented with progressive nonregenerative anemia. Clinicopathological abnormalities included severe nonregenerative anemia (packed cell volume [PCV]: 7%, aggregate reticulocytes: 1.12 × 10³/µl) and a hypoechogenic mass well-localized in the stomach. Bone marrow (BM) smears revealed increased particle hematopoietic cellularity with decreased myeloid:erythroid (M:E) ratios, no dysplasia of any lineage, and presence of erythroid precursors phagocytized by macrophages. The cat was diagnosed with presumptive precursor-targeted immune-mediated anemia (PIMA). The stomach mass was consistent with CD 20 positive T-cell lymphoma. The lymphoma was completely resected via surgery, and the PIMA was cured by immunosuppressive therapy. On day 410, both diseases have not recurred without medications. This is the first report of feline PIMA and concurrent gastrointestinal lymphoma.     

Abnormal erythroid cell proliferation and myelofibrosis in a cat

A cat was presented with severe progressive anemia despite marked erythroblastosis. The cat was negative for feline leukemia virus antigen and feline immunodeficiency virus antibody. Bone marrow cytology revealed an excess of erythroid cells with a predominance of prorubricytes and basophilic rubricytes. No response to immunosuppressive therapy was obtained, and a tentative diagnosis of myelodysplastic syndrome was made. The cat showed a partial response to low-dose cytarabine (20 mg/m(2) subcutaneously q24) but died 51 days after the 1st admission. Histopathological examination revealed fibrosis in the bone marrow and marked infiltration of erythroid cells into other organs.     

Uterine torsion and metabolic abnormalities in a cat with a pyometra

A 6-year-old, intact female, Russian Blue cat was presented with abdominal distention, vaginal discharge, and a firm tubular structure palpable in the mid-abdomen. Serum biochemical abnormalities included hyperkalemia, hyponatremia, and azotemia. Exploratory laparotomy revealed a pyometra with uterine torsion; an ovariohysterectomy was performed.     

Bone marrow hypoplasia associated with fenbendazole administration in a dog

A 1.5-year-old Doberman pinscher was presented with sudden-onset of fever and malaise. Twelve days prior to presentation, fenbendazole therapy was initiated for a suspected lungworm infection. Results of a complete blood count on presentation showed pancytopenia, while histopathological evaluation of a bone marrow core sample revealed bone marrow hypoplasia of undetermined etiology. Bactericidal antibiotics and fluid therapy, as well as discontinuation of fenbendazole administration, led to a complete resolution of clinical and hematological abnormalities within 15 days. An idiosyncratic reaction to fenbendazole was suspected based on the absence of infectious, neoplastic, autoimmune, and toxic etiologies, as well as resolution of clinical signs and pancytopenia upon drug withdrawal.     

Malignant mesenchymoma with widespread metastasis including bone marrow involvement in a dog

A male castrated Golden Retriever was presented for evaluation of a large mass over the left shoulder extending to the lower part of the neck that had been present for an extended period of time, but had a recent history of rapid growth. Previous aspirates of the mass were consistent with a lipoma. The mass was surgically excised and was diagnosed as an extraskeletal osteosarcoma based on histopathology. After surgery, the dog was initiated on a chemotherapy protocol with carboplatin and metronomic cyclophosphamide. He became neutropenic, anemic, and thrombocytopenic 14 days after the carboplatin treatment was administered. The neutropenia resolved, but the anemia and thrombocytopenia progressed. A bone marrow aspirate revealed erythroid hypoplasia, myeloid hyperplasia with a predominance of early precursors, and a subset of cells that made up 20% of the total population that were reported as bizarre and unclassifiable. These cells were discrete in nature and were thought to be hematopoietic in origin. The dog was euthanized due to deterioration of the clinical condition. On postmortem examination, widespread metastasis involving the lungs, liver, kidney, heart, and bone marrow was found. Histopathology of the tumor lesions determined 2 distinct malignant populations of liposarcoma and osteosarcoma, consistent with malignant mesenchymoma. However, the possibility of 2 separate neoplastic processes cannot be definitively excluded. This is the first report of bone marrow metastasis of a malignant mesenchymoma in a dog.