Bone marrow failure in a dog

A 7-month old Boxer bitch with lethargy and inappetence of several days' duration was found to have pancytopenia. A bone marrow aspirate contained many lymphocytes and immature myeloid cells but few erythrocyte precursors; marrow phagocytes appeared active and megakaryocytes were immature. Circumstantial evidence suggested that the cause of marrow failure was prior administration of thiacetarsamide, an organic arsenical. Recovery was spontaneous and within four weeks the haemo-gram was normal, except that platelet numbers were not fully restored.
The bitch was examined 6 months later because of a recurrence of signs, with several syncopic episodes during the preceding week. A severe non-regenerative anaemia was present, with absence of erythroid precursors from bone marrow. Neutrophil and platelet counts were normal. The cause of the erythrocyte aplasia was not determined. The dog was given blood transfusions, oxymetholone and prednisolone but died after one month. A post-mortem marrow sample contained many erythroid cells, some with morphological abnormalities suggesting dyserythropoiesis.     

Idiopathic aplastic anemia in a dog

A case of idiopathic aplastic anemia in a dog was characterized by pancytopenia and bone marrow aplasia. Erythroid colony-forming units (CFU-E) were not detected in bone marrow culture. Addition of the dog's serum to CFU-E culture from control dogs failed to suppress colony formation, suggesting that humorally-mediated suppression at the CFU-E level was not a cause of the aplastic anemia.     

Myelophthisic pancytopenia in a pony mare

Myelophthisic pancytopenia was diagnosed in a 10-year-old pony mare with a history of recurring colic and anemia. Physical findings were unremarkable, with the exception of pale mucous membranes. Hematologic analysis revealed nonregenerative pancytopenia. Testing for equine infectious anemia and antiglobulin (Coombs) yielded negative results. The mare was treated with antibiotics, boldenone undecylenate, and corticosteroids, but a regenerative bone marrow response was not seen. Postmortem examination revealed severe myelofibrosis and multiple sites of extramedullary hematopoiesis. Myelophthisic pancytopenia develops when a space-occupying lesion destroys sufficient bone marrow or disturbs marrow architecture, resulting in decreased production capacity. Pancytopenia in the pony of this report resulted from inadequate production of blood cellular components secondary to replacement of the bone marrow by myelofibrosis. Cause of the myelofibrosis was not identified.     

Aplastic anemia in cats - clinicopathological features and associated disease conditions 1996-2004

A retrospective study of 128 feline bone marrow reports identified 13 cases of aplastic anemia. Clinical diagnoses included chronic renal failure (n=5), feline leukemia virus infection (n=2), hyperthyroidism treated with methimazole (n=1) and idiopathic aplastic anemia (n=5). In some cats, starvation may play a role in the development of marrow aplasia. Some cats with aplastic anemia can have prolonged survival without resolution of the pancytopenia.     

Pancytopenia in two horses following administration of potentiated sulfonamide antimicrobials

Adverse drug reactions to potentiated sulfonamide antimicrobial drug combinations have been reported in many species, including horses. This report describes the occurrence of pancytopenia in 2 horses, one subsequent to an immune mediated reaction and the other bone marrow aplasia following the administration of trimethoprim and sulfadimidine. These cases highlight the importance of judicious use of antimicrobial agents and describe adverse drug reactions in horses receiving potentiated sulfonamide antimicrobials.     

ERYTHROCYTE APLASIA IN A DOG

Erythrocyte aplasia was diagnosed in a 6-year-old dog which had severe non-regenerative anaemia with depletion of erythroid cells in the bone marrow but normal production of granulocytes and platelets. Treatment with blood transfusions, testosterone and dexamethasone was unsuccessful. The dog died 46 days after initial examination as a result of anaemia, transfusion reactions, and toxaemia from an ascending urinary tract infection.     

Toxic effects of mebendazole at high dose on the haematology of red-legged pademelons (Thylogale stigmatica)

OBJECTIVE: To investigate the effects of mebendazole at high dose on the haematology of macropods. Experimental. PROCEDURE: Five red-legged pademelons (Thylogale stigmatica) were dosed orally with mebendazole at 50 mg/kg/d for 5 to 6 days. Two control pademelons were dosed with water. Regular blood samples were taken for haematology over 20 days. RESULTS: All four treated pademelons sampled at 5 days developed severe leucopenia and neutropenia, moderate lymphopenia, thrombocytopenia, eosinopenia and monocytopenia, as well as bone marrow aplasia within 5 to 11 days after the first mebendazole dose. Four pademelons died unexpectedly or became ill and were euthanased 5 to 11 days after the first dose while the other animal recovered after 5 days of illness. Necropsy revealed systemic infection with opportunistic enteric bacteria, non-suppurative inflammation in tissues, haemorrhage and ulceration of the gastrointestinal tract. CONCLUSIONS: Red-legged pademelons rapidly develop bone-marrow aplasia and subsequent septicaemia after administration of high doses of mebendazole. Mebendazole at high doses should not be used for macropods.     

Bone marrow necrosis and myelophthisis: manifestations of T‐cell lymphoma in a horse

Abstract: A 14‐year‐old spayed American Paint mare was evaluated for mild colic, anorexia, pyrexia, and pancytopenia. Physical examination revealed mild tachycardia, tachypnea, and pale mucous membranes. Serial laboratory analyses revealed progressive pancytopenia, hyperfibrinogenemia, and hyperglobulinemia. A few large atypical cells were observed in peripheral blood smears. Results of tests for equine infectious anemia and antipenicillin antibody were negative. Serum protein electrophoresis indicated a polyclonal gammopathy. Smears of bone marrow aspirates contained hypercellular particles, but cell lines could not be identified because the cells were karyolytic, with pale basophilic smudged nuclei and lack of cellular detail. A diagnosis of bone marrow necrosis was made. Treatment consisted of antimicrobials, nonsteroidal anti‐inflammatory drugs, and corticosteroids. The pyrexia resolved; however, the pancytopenia progressively worsened and petechiation and epistaxis developed. The horse was humanely euthanized. Postmortem examination revealed a diffuse round cell neoplasm infiltrating the kidneys, spleen, lymph nodes, lungs, and bone marrow. Immunophenotyping results (CD3+, CD79α−) indicated the neoplastic cells were of T‐cell lineage. Infiltration of lymphoma cells into the bone marrow appeared to have resulted in severe myelophthisis and bone marrow necrosis. Bone marrow necrosis has been associated previously with lymphoma in humans and dogs. To our knowledge, this is the first reported case of lymphoma resulting in bone marrow necrosis in a horse.     

Primary pure red cell aplasia in dogs: 13 cases (1996-2000)

OBJECTIVES: To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA). DESIGN: Retrospective study. ANIMALS: 13 dogs with severe nonregenerative anemia and bone marrow erythroid aplasia. PROCEDURES: Medical records of dogs determined to have PRCA on the basis of results of blood and bone marrow analysis between 1996 and 2000 were reviewed. Criteria for inclusion in the study were severe nonregenerative anemia (Hct < 20%; reticulocyte count < 1.0%), selective erythroid aplasia in bone marrow, and lack of underlying diseases that may have caused the anemia. RESULTS: Median age of dogs was 6.5 years. Females were significantly overrepresented. Median Hct was 10%, and median reticulocyte count was 0.1%. Direct Coombs' test results were negative for all dogs tested, and spherocytosis was evident in 2 dogs. All dogs were treated with prednisolone, and 2 dogs were treated with prednisolone and cyclophosphamide. Responses to treatment were complete, partial, and poor in 10, 1, and 2 dogs, respectively. Median time required to achieve an increase of 5% or more in Hct was 38 days, and median time to complete remission was 118 days. Of 10 dogs for which follow-up information was available, only 1 required long-term immunosuppressive treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with PRCA appear to respond readily to treatment with immunosuppressive drugs; however, hematologic responses may not be observed for weeks to months after initiation of treatment.     

Reproduction of bovine neonatal pancytopenia (BNP) by feeding pooled colostrum reveals variable alloantibody damage to different haematopoietic lineages

Bovine neonatal pancytopenia (BNP) is a recently described haemorrhagic disease of calves characterised by thrombocytopenia, leucopenia and bone marrow depletion. Feeding colostrum from cows that have previously produced a BNP affected calf has been shown to induce the disease in some calves, leading to the hypothesis that alloantibodies in colostrum from dams of affected calves mediate destruction of blood and bone marrow cells in the recipient calves. The aims of the current experimental study were first to confirm the role of colostrum-derived antibody in mediating the disease and second to investigate the haematopoietic cell lineages and maturation stages depleted by the causative antibodies. Clinical, haematological and pathological changes were examined in 5 calves given a standardised pool of colostrum from known BNP dams, and 5 control calves given an equivalent pool of colostrum from non-BNP dams. All calves fed challenge colostrum showed progressive depletion of bone marrow haematopoietic cells and haematological changes consistent with the development of BNP. Administration of a standardised dose of the same colostrum pool to each calf resulted in a consistent response within the groups, allowing detailed interpretation of the cellular changes not previously described. Analyses of blood and serial bone marrow changes revealed evidence of differential effects on different blood cell lineages. Peripheral blood cell depletion was confined to leucocytes and platelets, while bone marrow damage occurred to the primitive precursors and lineage committed cells of the thrombocyte, lymphocyte and monocyte lineages, but only to the more primitive precursors in the neutrophil, erythrocyte and eosinophil lineages. Such differences between lineages may reflect cell type-dependent differences in levels of expression or conformational nature of the target antigens.     

Cephalosporin-induced changes in the ultrastructure of canine bone marrow

Fourteen healthy dogs were given 540 to 840 mg/kg of cefazedone (Refosporen) intravenously for up to 4 months or until peripheral blood cell count were depressed. Within 6 to 10 weeks treated dogs developed pancytopenia (5/14), thrombocytopenia (11/14), moderate to severe neutropenia (8/14), and/or normocytic anemia with erythroblastemia (8/14). Ultrastructural changes in bone marrow of severely cytopenic dogs included mitochondrial damage in hematopoietic and nonhematopoietic cells, thickening of endosteal bone lining layers, increased adventitial coverage of vascular sinuses, and an increased number of active macrophages. Swollen, ruptured mitochondria were in erythroid, granulocytic, and megakaryocytic cells, and, to a lesser extent, in macrophages, reticular endothelial, and bone lining cells. Maturation arrest was evident in both erythroid and granulocytic cell lines. There was also evidence of ineffective erythropoiesis and granulopoiesis. None of these changes were observed in bone marrow of controls, treated dogs that did not develop cytopenia, or dogs allowed to recover after cessation of dosing.     

A retrospective study of aplastic pancytopenia in the dog: 9 cases (1996-2003)

BACKGROUND: Aplastic pancytopenia is defined by the presence of pancytopenia in blood and a hypocellular bone marrow with the hematopoietic space replaced by adipose tissue. Several causes of acquired aplastic pancytopenia are known; however, in some cases, an underlying cause is never determined. OBJECTIVE: The objective of this retrospective study was to identify the incidence, potential causes, and outcome of aplastic pancytopenia in dogs. METHODS: Bone marrow cytologic and core biopsy reports were reviewed to identify dogs diagnosed with aplastic pancytopenia between July 1, 1996 and June 30, 2003. Four-hundred eighty-six bone marrow reports that included aspirate and core biopsy evaluations were reviewed. Signalment, treatment given, previous and current disease conditions, clinical signs of disease, clinical laboratory data, therapy, response to therapy, and survival time were recorded. RESULTS: Nine dogs (1.85% of bone marrow samples reviewed) met the criteria for inclusion. Two dogs (22%) had associated diseases that included monocytic ehrlichiosis and Sertoli cell tumor. In 7 dogs (78%), the cause of aplastic pancytopenia could not be definitively determined, although an idiosyncratic drug reaction to griseofulvin was suspected in 1 of the dogs. The median age of dogs diagnosed with aplastic pancytopenia was 3.2 years, and apparent breed or sex predilection was not identified. Median HCT, total WBC count, and platelet count on the day of presentation were 21.8%, 1.0 x 10(3)/microL, and 2.0 x 10(3)/microL, respectively. Six of 9 dogs diagnosed with aplastic pancytopenia died or were euthanized within 21 days. Two dogs had complete hematologic recovery. One dog was living 3 years after diagnosis, but hematologic recovery was never documented. CONCLUSIONS: Aplastic pancytopenia is diagnosed infrequently and idiopathic aplastic pancytopenia may account for up to 67% or more of canine cases. Although the prognosis is guarded, some dogs with aplastic pancytopenia recover.     

Bone marrow necrosis in a cat infected with feline leukemia virus

A one-year old castrated male cat was admitted to the hospital with vomiting and diarrhea. Laboratory examination revealed pancytopenia and positive for FeLV antigen. A bone marrow examination indicated necrosis of the nucleated cells. Based on these findings, the cat was diagnosed as bone marrow necrosis. Pancytopenia was effectively treated with corticosteroids. Re-examination of the bone marrow confirmed a recovery of normal hematopoietic cells with a infiltration of many macrophages. It is strongly suspected that the bone marrow necrosis in this case could be associated with a bone marrow suppression due to FeLV infection.     

Aplastic anemia associated with trimethoprim-sulfadiazine and fenbendazole administration in a dog

A dog that was treated with trimethoprim-sulfadiazine and fenbendazole developed transient aplastic anemia. The onset of bone marrow aplasia at 14 days after initiation of treatment and remission of it after cessation of treatment suggested that the aplasia was drug-induced. A hematologically normal dog treated with the same drug combination failed to develop hematologic dyscrasia. Because of the potential toxic effects of trimethoprim-sulfadiazine and/or fenbendazole, animals under treatment with this combination should be monitored by use of periodic CBC.     

Pancytopenia caused by bone marrow aplasia in a horse

Pancytopenia was evaluated in a mature Quarter Horse gelding. A diagnosis of bone marrow aplasia was made on the basis of bone marrow hypocellularity. History of drugs administered included penicillin, oxytetracycline, trimethoprim-sulfadiazine, phenylbutazone, dipyrone, flunixin meglumine, and isoxsuprine. Clinical remission was observed after treatment with glucocorticoids, androgens, and broad-spectrum antimicrobials.     

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.     

Sera from dams of calves with bovine neonatal pancytopenia contain alloimmune antibodies directed against calf leukocytes

Bovine neonatal pancytopenia (BNP) is a bleeding and pancytopenic syndrome in neonatal calves, which recently emerged all over Europe. The present study tested whether antibodies directed against calf leukocytes are present in sera from known BNP dams. Sera from BNP dams (n=11) were combined with leukocytes from 11 calves (5 BNP survivors and 6 controls). After adding a fluorescein conjugated F(ab')(2) fragment of rabbit anti-bovine IgG (H&L) the level of antibody binding was measured by flow cytometry. As control groups both sera from dams from BNP affected (n=48) as from unaffected (n=54) herds were combined with leukocytes from the same calves. With sera from BNP dams, antibody binding could be visualised by immunofluoresence in both peripheral blood as in bone marrow smears. Mean fluoresence intensity values of all leukocyte subpopulations were significantly higher for the BNP dams compared to both control groups (P<0.01). BNP dams showed significantly more antibody binding on multiple leukocyte subpopulations of both BNP survivors and control calves and this from cut off values of MFI 100 onwards (P<0.01). The BNP survivor calves reacted significantly more often with sera from the BNP dams than the control calves (P<0.01). In conclusion the present study supports the hypothesis that BNP is an immune-mediated disease.     

Pancytopenia Secondary to Lymphoid Leukemia in Three Horses

Pancytopenia was observed in two 3-year-old geldings and one 11-year-old mare. All horses had a brief history (2 days to 4 weeks) of fever, anorexia, and depression. One of the three horses had blast cells present on a peripheral blood smear. Examination of the bone marrow showed substantial infiltration with neoplastic lymphoid cells. At necropsy, neoplastic cells were restricted to the bone marrow in one horse, present in bone marrow, liver, and spleen in the second horse, and reported in multiple tissues in the third horse, including bone marrow, kidneys, lung, myocardium and lymph nodes. The value of a bone marrow aspirate and core biopsy in the investigation of pancytopenia is highlighted. (Journal of Veterinary Internal Medicine 1993; 7:360–363. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Idiopathic pure red cell aplasia and nonregenerative immune-mediated anemia in dogs: 43 cases (1988-1999)

OBJECTIVE: To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA) and idiopathic nonregenerative immune-mediated anemia (NRIMA). DESIGN: Retrospective study. ANIMALS: 43 dogs with severe nonregenerative anemia. PROCEDURE: Medical records of dogs determined to have PRCA, NRIMA, or ineffective erythropoiesis on the basis of bone marrow analysis between 1988 and 1999 were reviewed. Criteria for inclusion were > or = 5-day history of severe nonregenerative anemia (Hct < 20%; < 60.0 x 10(3) reticulocytes/microliter) with no underlying diseases. Information was retrieved on signalment, clinical signs, laboratory test results, treatment, and outcome. RESULTS: Median age of the dogs was 6.5 years. Spayed females and Labrador Retrievers were significantly overrepresented. Median Hct was 11% with no evidence of regeneration (median, 1.5 x 10(3) reticulocytes/microliter). Direct Coombs' test results were positive in 57% of dogs. Biochemical abnormalities included hyperferremia and high percentage saturation of transferrin. Bone marrow findings ranged from PRCA (5%) to erythroid hyperplasia (55%). Myelofibrosis was common. Dogs were treated with immunosuppressive drugs and the response was complete, partial, and poor in 55, 18, and 27% of the dogs, respectively. Mortality rate was 28%. CONCLUSIONS AND CLINICAL RELEVANCE: An immune-mediated pathogenesis should be considered in dogs with severe, nonregenerative anemia, normal WBC and platelet counts, hyperferremia, mild clinical signs, and no evidence of underlying disease. Bone marrow findings range from the rare PRCA to erythroid hyperplasia. Myelofibrosis is often detected in affected dogs and may prevent bone marrow aspiration.     

Oestrogen-induced bone marrow aplasia in a dog with a Sertoli cell tumour

A 10-year-old male Drahthaar dog with unilateral cryptorchidism was examined because of feminisation and myelotoxicity. Radiography and ultrasonography revealed an abdominal mass which was surgically removed. The mass was identified as a Sertoli cell tumour on histological examination. Findings on bone marrow examination were compatible with aplasia due to the oestrogens secreted by the tumoral cells. Treatment with fluids, antibiotics, whole blood transfusions, corticosteroids and lithium carbonate was unsuccessful. Survival time was 22 days after surgery.