Neutropenia in dogs and cats: a retrospective study of 261 cases

Case records of 232 dogs and 29 cats with neutropenia were reviewed to examine the spectrum of underlying etiologies causing the neutropenia. Six etiological categories included nonbacterial infectious disease; increased demand due to marked inflammation, bacterial sepsis, or endotoxemia; drug-associated neutropenia; primary bone-marrow disease; immune-mediated neutropenia; and diseases of unclear etiology. The largest single category associated with the development of neutropenia was nonbacterial infectious disease (e.g., feline leukemia virus [FeLV], feline immunodeficiency virus [FIV], histoplasmosis, cryptococcosis, and parvovirus), with parvovirus infection accounting for 47.1% of all cases. The least common (0.38%) cause was naturally occurring immune-mediated neutropenia.     

Azathioprine for treatment of immune-mediated thrombocytopenia in two horses.

Azathioprine, a thiopurine antimetabolite used in the treatment of immune-mediated thrombocytopenia in human beings and dogs, was used in 2 cases of immune-mediated thrombocytopenia in horses that failed to respond to corticosteroid therapy alone. Platelet counts were increased to acceptable values in both horses. One horse returned to a successful racing career, and the other was euthanatized after developing renal disease and mild laminitis.     

Risk factors for sterile hemorrhagic cystitis in dogs with lymphoma receiving cyclophosphamide with or without concurrent administration of furosemide: 216 cases (1990-1996)

OBJECTIVES: To determine incidence and identify predisposing factors for sterile hemorrhagic cystitis (SHC) in dogs with lymphoma that were treated with cyclophosphamide and to evaluate whether furosemide administered i.v. concurrently with cyclophosphamide decreased the incidence of SHC. DESIGN: Retrospective study. ANIMALS: 216 dogs with lymphoma. PROCEDURE: Medical records of dogs with lymphoma that received cyclophosphamide chemotherapy in accordance with 1 of 2 protocols, with or without concurrent i.v. administration of furosemide, were examined. Data for the 2 groups were analyzed to determine the incidence and predisposing factors (age, breed, sex, weight, previous or preexisting disease, previous or preexisting urinary tract infection, neutropenia, azotemia, dose, and number of cyclophosphamide treatments) for cyclophosphamide-associated SHC. RESULTS: Cyclophosphamide-associated SHC developed in 12 of 133 (9%) dogs that had not received concurrent administration of furosemide and cyclophosphamide treatments; of the 83 dogs that had received furosemide, only 1 (1.2%) developed SHC. Dogs receiving cyclophosphamide and furosemide concurrently were significantly less likely to develop SHC than dogs that did not receive furosemide. Dogs with previous or preexisting immune-mediated disease were significantly more likely to develop cyclophosphamide-associated SHC. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results suggested an association between i.v. administration of furosemide concurrently with cyclophosphamide and decreased incidence of cyclophosphamide-associated SHC. Incidence of cyclophosphamide-associated SHC was similar in treated dogs that did not receive concurrent furosemide to that observed for other studies in which cyclophosphamide was administered orally. Cyclophosphamide-associated SHC appeared to develop early during the course of chemotherapy when furosemide was not administered concurrently with cyclophosphamide.     

Evaluation of clinicopathologic features, response to treatment, and risk factors associated with idiopathic neutropenia in dogs: 11 cases (1990-2002)

OBJECTIVE: To evaluate the clinicopathologic features, response to treatment, and risk factors associated with idiopathic neutropenia in dogs. DESIGN: Retrospective case series. ANIMALS: 11 dogs. PROCEDURES: Medical records of dogs with idiopathic neutropenia were reviewed. Signalment, history, clinical signs, and response to treatment were recorded and compared with that in dogs with neutropenia attributable to known causes and to dogs without neutropenia (controls). RESULTS: Compared with dogs with neutropenia attributable to known causes, dogs with idiopathic neutropenia had lower neutrophil counts and were younger. When compared with control dogs, age < 4 years was identified as a risk factor for developing idiopathic neutropenia. In all dogs with idiopathic neutropenia, remission of neutropenia occurred within 18 days after administration of prednisone (2 to 4 mg/kg [0.9 to 1.8 mg/lb], PO, daily) and no serious complications or infections developed. CONCLUSIONS AND CLINICAL RELEVANCE: An immune-mediated pathogenesis should be considered for dogs with idiopathic neutropenia in which the cause is not known. Severe neutropenia and young age were significantly associated with idiopathic neutropenia in dogs. Prognosis appeared to be excellent with prednisone treatment.     

Intravenous Human Immunoglobulin for the Treatment of Immune-Mediated Hemolytic Anemia in 13 Dogs

Intravenous immunoglobulin (IVGG) was administered to 13 of 37 dogs with immune-mediated hemolytic anemia. All dogs received concurrent prednisone therapy, 14 dogs also received cyclophosphamide; and a single dog each received cyclosporine, azathioprines, and danazol. Dogs that responded to prednisone therapy without IVGG generally did so within 7 days (mean ± standard deviation = 5.6 ± 2.9 days). Intravenous immunoglobulin was administered after 10.4 ± 6.6 days of prednisone therapy as an intravenous infusion of 0.5 g/kg (range 0.25 to 0.73 g/kg). Eleven dogs received a single treatment, 2 dogs each received 2 treatments. No relevant adverse effects were noted. Eleven dogs had an increase in PCV of at least 4% 2.2 ±1.5 days after IVGG infusion. In 10 of these dogs, the PCV continued to increase until the time of hospital discharge. One responder died 1 hour after the increase in PCV, 1 dog was euthanized within 24 hours of IVGG administration, and 1 dog had no response over a period of 13 days. Results of this study suggest that IVGG therapy may be of value in dogs with immune-mediated hemolytic anemia that do not respond within 7 days of appropriate corticosteroid therapy.     

Dermatologic disorders in dogs with diabetes mellitus: 45 cases (1986-2000)

OBJECTIVE: To characterize skin lesions and causative infections in diabetic dogs and evaluate other potential causes of dermatologic disorders, including concurrent endocrinopathies, allergic skin disease, and long-term corticosteroid administration. DESIGN: Retrospective study. ANIMALS: 45 dogs with diabetes mellitus (DM) that were examined by dermatologists. PROCEDURE: Medical records were reviewed for signalment; allergic conditions prior to development of DM; prior corticosteroid administration; and results of dermatologic examinations, ear and skin cytologic examinations, skin scrapings for parasites, bacteriologic and fungal culturing of ear and skin specimens, histologic examinations, and endocrine testing. RESULTS: Bacterial skin infection was the most common dermatologic disorder (n = 38 [84%]), followed by otitis (26 [58%]) and Malassezia-induced dermatitis (19 [42%]). Twenty-two (49%) dogs had pruritic skin disease consistent with allergic dermatitis, which preceded diagnosis of DM. Prior corticosteroid administration was reported in 21 (47%) dogs. Concurrent hyperadrenocorticism was diagnosed in 13 (29%) dogs, and concurrent hypothyroidism was diagnosed in 5 (11%) dogs. Iatrogenic hyperadrenocorticism was diagnosed in 1 additional dog. Only 10 (22%) dogs did not have a documented concurrent endocrinopathy or allergic disease that could have caused the dermatitis. CONCLUSIONS AND CLINICAL RELEVANCE: Bacterial and yeast-induced dermatitis and otitis develop in dogs with DM. Many diabetic dogs with dermatologic problems have a preexisting allergic condition, history of prior corticosteroid administration, or concurrent endocrinopathy that may be a more likely cause of dermatologic problems than DM alone.     

Pattern of Coombs' test reactivity has diagnostic significance in dogs with immune-mediated haemolytic anaemia

OBJECTIVES: To investigate the clinical significance of the pattern of Coombs' test reactivity in dogs with immune-mediated haemolytic anaemia. METHODS: Sixty-five anaemic dogs with a positive Coombs' test were included. Coombs' testing was performed at 4 and 37 degrees C with polyvalent canine Coombs' reagent and antisera specific for each of canine immunoglobulin G, immunoglobulin M and complement factor C3. The impact of performing testing with only polyvalent antiserum at 37 degrees C was assessed. Chi-squared tests were used to compare Coombs' test reactivity in dogs with primary immune-mediated haemolytic anaemia (group A) and in dogs with concurrent/underlying disease (group B). Following Bonferroni correction, significance was set at P < or = 0.003. RESULTS: Eleven dogs would have been regarded as Coombs' negative had they been tested with polyvalent antiserum at 37 degrees C alone. Group A dogs were significantly more likely to be positive with polyvalent antiserum and/or anti-dog immunoglobulin G at 4 and/or 37 degrees C (P < or = 0.001) and tended to be less likely to be positive with anti-dog immunoglobulin M at 4 degrees C (P=0.040). CLINICAL SIGNIFICANCE: Testing of anaemic dogs with polyvalent Coombs' reagent at 37 degrees C was less sensitive than testing with monovalent reagents at 4 and 37 degrees C. The pattern of Coombs' test reactivity differed significantly between dogs with primary immune-mediated haemolytic anaemia and those with concurrent/underlying disease.     

Concurrent Diseases and Conditions in Dogs with Splenic Vein Thrombosis

Background: Splenic venous thrombosis (SVT) is usually considered an incidental finding on abdominal ultrasound examination but can indicate the presence of underlying disease. Concurrent disease processes and conditions in dogs with SVT have not been identified previously. Objectives: To identify concurrent diseases and conditions in dogs with SVT. Animals: Eighty dogs with SVT. Methods: Retrospective review. Medical records from 1994 through 2008 were searched for dogs with SVT identified by ultrasound examination. These records were then reviewed for signalment, medical history, clinicopathologic testing, diagnostic imaging, and clinical diagnosis. Results: The most common concurrent conditions were neoplasia (54%), exogenous corticosteroid administration (43%), systemic inflammatory response syndrome (26%), disseminated intravascular coagulation (20%), pancreatitis (18%), and immune‐mediated disease (16%). The most common neoplastic disease was lymphoma, and the most common immune‐mediated disease was immune‐mediated hemolytic anemia. Protein‐losing nephropathy and naturally occurring hyperadrenocorticism were identified in <10% of the dogs. Concurrent splenic infarcts were identified in 33% of dogs, and concurrent portal vein thrombi were found in 18% of dogs. Conclusions: SVT is a sonographic finding of clinical importance, and dogs with SVT can have 1 or more coexisting diseases.     

Evaluation of platelet activation in canine immune-mediated haemolytic anaemia

Objectives : To establish whether heightened platelet activation is a common feature of canine immune-mediated haemolytic anaemia, and to evaluate the hypothesis that platelet activation plays a role in the pathogenesis of thromboembolism. Methods : Using whole-blood flow-cytometric analysis, the proportion of activated platelets and platelet-leucocyte aggregates in blood samples from 14 dogs with immune-mediated haemolytic anaemia and 14 healthy dogs was calculated. General linear models with binomial errors were used to compare groups. Results from the immune-mediated haemolytic anaemia-affected dogs were then correlated with established risk factors for thromboembolism in canine immune-mediated haemolytic anaemia, D-dimer concentration and antithrombin activity. Results : There was a strong correlation between platelet activation and severe thrombocytopenia, with heightened platelet activation being observed predominantly in severely thrombocytopenic dogs. Clinical Significance : Dogs with immune-mediated haemolytic anaemia, particularly those with concurrent severe thrombocytopenia, are likely to have heightened platelet activation, which may play a role in the pathogenesis of thromboembolism.     

Immune-mediated Hemolytic Anemia and Thrombocytopenia in the Dog: A retrospective study of 55 cases diagnosed from 1979 through 1983 at the Western College of Veterinary Medicine

All recognized cases (n = 55) of immune-mediated hemolytic anemia and immune-mediated thrombocytopenia in dogs presented to the Western College of Veterinary Medicine from 1969 through 1983 were reviewed. Specific areas of concern were: association with other conditions, therapeutic response, prognosis, relapse rate and final outcome. Of these 55 cases, 19 were immune-mediated hemolytic anemia, 26 were immune-mediated thrombocytopenia and 10 were both immune-mediated hemolytic anemia and thrombocytopenia. Females were slightly over-represented and the mean age was 6.4 years. Therapy consisted of various combinations of immuno-suppressive drugs and in some cases, whole blood transfusion and splenectomy. No firm conclusions could be made regarding therapeutic efficacy, as a result of variation in treatment protocol and the occasional unavailability of follow-up data. Well over half of all cases were diagnosed as idiopathic. Precipitating factors or diseases most frequently implicated in secondary immune-mediated thrombocytopenia or hemolytic anemia were: recent vaccination, drug therapy, obstetrical complications, stress, recent viral infection and neoplasia. Twice as many cases of immune-mediated hemolytic anemia were seen in the cooler months (October to March), although this could not be related to antibody class or thermal reactivity. Immune-mediated thrombocytopenia both as a single disease and combined with immune-mediated hemolytic anemia had no seasonal incidence. History, clinical findings and hematological and clinical chemistry findings were consistent with data previously reported, with the exception of icterus, which appeared to be of higher incidence than most reports, being present in almost 50% of immune-mediated hemolytic anemia cases. Just over half of all dogs survived, although the survival rate was highest for immune-mediated hemolytic anemia, followed closely by immune-mediated thrombocytopenia and lowest for the combined disease. Immune-mediated thrombocytopenia most frequently ran a relapsing course requiring long-term or intermittent therapy.     

Spontaneous systemic hypertension in dogs: five cases (1981-1983)

Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that were examined because of apparent blindness caused by intraocular hemorrhage and/or retinal detachment. Secondary causes of hypertension, including renal, adrenal, and thyroid disease, were investigated. Four of the dogs had glomerulonephropathy, renal insufficiency, and proteinuria. Four dogs had compensatory cardiac hypertrophy. Hypertension in 4 of 5 dogs was associated with glomerulosclerosis with chronic renal insufficiency, bilateral adrenocortical hyperplasia, adrenocortical adenoma with renal amyloidosis, and immune-mediated glomerulonephritis with chronic renal insufficiency, respectively. The fifth dog was determined to have essential hypertension. The dogs were treated for their primary diseases. Sodium restriction alone was inadequate to reduce blood pressure; 4 of the dogs also required antihypertensive medications.     

Sclerosing Encapsulating Peritonitis in Four Dogs and a Cat

Sclerosing encapsulating peritonitis (SEP) was diagnosed in four dogs and one cat. Clinical signs included vomiting, abdominal pain, palpable abdominal mass, and ascites. The abdominal fluid was red-tinged and contained large numbers of red blood cells, macrophages, mixed inflammatory cells, reactive mesothelial cells, and fibroblasts. At surgery, the typical appearance was of multiple surfaces covered with granulation tissue or fibrous tissue or both. Multiple adhesions were often present. Causes of SEP included steatitis, fiberglass ingestion, and bacterial infection. Treatment included administration of antibiotic, corticosteroid, and diuretic medications. The major long-term management problems were chronic weight loss, ascites, and progression of concurrent disease.     

Diagnostic investigations in 101 dogs with pyrexia of unknown origin

Records from 101 dogs presented for investigation of unexplained pyrexia were reviewed. The most common diagnosis was immune-mediated disease (22 per cent of cases), with immune-mediated polyarthritis accounting for 20 per cent of all diagnoses. The frequency of positive results obtained in investigative tests was also assessed. Cytological and radiological examinations provided a high diagnostic success rate, although routine haematology and plasma biochemistry were also useful screening tests. On the basis of these results it is suggested that, in the investigation of unexplained pyrexia, a diagnosis of immune-mediated polyarthritis should be excluded before less common diagnoses are considered.     

Splenectomy as an adjunctive treatment for dogs with immune-mediated hemolytic anemia: ten cases (2003–2006)

Objective – To describe the patient population, disease severity, and outcome in dogs with immune-mediated hemolytic anemia (IMHA) that underwent splenectomy. To compare presurgical and postsurgical data.
Design – Retrospective case series.
Setting – Emergency clinic/referral hospital.
Animals – Ten dogs diagnosed with IMHA.
Interventions – Splenectomy in addition to standard medical management for IMHA.
Measurements – Medical records of 10 dogs with IMHA, in which a splenectomy was performed were reviewed. The population was analyzed with regards to physical and clinicopathologic data, severity, treatment, and outcome. Outcome was defined as survival at 30 days, percentage of dogs on medications at 30 days, and number of relapses documented by 30 days. The presurgical and postsurgical PCV and transfusion requirements were documented and compared for each dog.
Results – Nine of 10 dogs survived to 30 days. Four of the 9 that survived were not on any immunosuppressive medications. There were no relapses during the 30 days. The 3-day postsplenectomy PCVs were significantly higher than presplenectomy. The number of transfusions administered postsplenectomy was significantly less than those administered presplenectomy.
Conclusion – The use of splenectomy may be associated with an improved outcome in dogs with IMHA.     

Acquired amegakaryocytic thrombocytopenia--four cases and a literature review

Acquired amegakaryocytic thrombocytopenla was diagnosed in four dogs. Initial platelet counts in all four dogs were less than 50,000 x 10(9)/litre and initial bone marrow examinations revealed megakaryocytic hypoplasia with minimal changes in the erythroid and myeloid cell lines. Two dogs had evidence of idiopathic immune-mediated disease and two dogs had evidence of associated infectious disease. One dog had a positive antibody titre to Borrella burgdorferi, and one dog had positive titres to both Ehrlichia canis and B. burgdorferi. Treatment consisted of prednisone and cyclophosphamide for the dogs with presumptive immune-mediated disease, and prednisone and tetracycline for the dogs with positive antibody titres to the Infectious organisms. Both dogs with evidence of associated infectious disease responded to treatment. A postmortem examination did not reveal the underlying aetiology in the two dogs with presumptive idiopathic immune-mediated disease.     

Ulcerative otitis externa responsive to immunosuppressive therapy in two dogs

Two middle-aged dogs were presented with bilateral severe ulcerative otitis externa without previous history of disease or evidence of other skin disease. Based on the exclusion of microbial infection and other primary causes, histopathological findings and response to immunomodulatory treatment, a diagnosis of presumed immune-mediated ulcerative otitis externa was made in both cases. However, the two cases differed with regard to their histopathological characteristics and the course of the disease. This report indicates that primary ulcerative disease needs to be considered in cases of ulcerative otitis externa which are unresponsive to appropriate antimicrobial therapy.     

Detection of antiplatelet immunoglobulin in thrombocytopenic dogs

Indirect enzyme-linked immunosorbent assays (ELISA) were used to detect platelet-associated immunoglobulin in sera from dogs with immune-mediated thrombocytopenia (IMT) and/or other autoimmune syndromes. One ELISA, utilizing whole platelets as the antigen substrate, readily detected antibody associated with platelets, either as specific, antiplatelet antibody or as immune complexes. This assay apparently lacked specificity because of the position reactions with sera from dogs with miscellaneous autoimmune disorders and no concurrent thrombocytopenia. Although the second ELISA, utilizing immunoaffinity purified platelet antigens was not influenced as much by immune complexes, absorbance values apparently were slightly increased. However, a small number of dogs with non-thrombocytopenic autoimmune disease tested positive. Immunoadsorption and Western immuno-blotting techniques demonstrated a complex pattern of specificities for antiplatelet antibodies. Clinical significance of these findings is discussed.     

Use of inhaled medications to treat respiratory diseases in dogs and cats

Noninfectious disorders of the respiratory tract, including laryngitis, tracheitis, bronchitis, and asthma are common problems in dogs and cats. Traditional therapies have often included corticosteroids and bronchodilators given by mouth or injection. Side effects of this form of treatment can be severe and can result in cessation of therapy. Inhaled corticosteroid drugs are not as absorbed into the systemic circulation, do not result in significant side effects, and are now the standard of care for dogs and cats with respiratory diseases that would otherwise be treated with systemic medications.     

Pulmonary Thromboembolism in 29 Dogs: 1985–1995

Pulmonary thromboembolism (PTE) occurs as a complication to a number of commonly encountered clinical diseases. Antemortem recognition of this life-threatening disorder is hampered by nonspecificity of clinical signs. This retrospective study was performed to analyze clinical features, laboratory findings, imaging abnormalities, and concurrent postmortem diagnoses in 29 dogs with confirmed pulmonary embolism. A variety of clinicopathologic and radiographic abnormalities were noted but there were no pathognomonic findings for PTE. Arterial blood gas analyses were performed in 15 (52%) of 29 dogs; 12 (80%) of 15 exhibited hypoxemia and 15 (100%) of 15 had increased alveolar-arterial oxygen gradients. Response to supplemental O2 was variable and did not correlate with the presence or absence of additional pulmonary pathology on postmortem. At postmortem, 25 (86%) of 29 dogs had grossly visible emboli, 17 (59%) of 29 dogs had multiple disease processes, and 16 (55%) of 29 dogs had additional pulmonary pathology. PTE was suspected antemortem in 11 (38%) of 29 dogs. In dogs with respiratory signs consistent with PTE, the condition was a differential diagnosis in 11 of 17 animals; all had diseases previously reported to be associated with PTE. Neoplasia, systemic bacterial disease, and immune-mediated hemolytic anemia were diagnosed most frequently.     

Chronic Pancreatitis in Dogs

Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.