Utility and prognostic significance of leukocyte ratios in dogs with Primary Immune-Mediated Hemolytic Anemia.

Canine immune-mediated hemolytic anemia (IMHA) is a life-threatening condition that is commonly associated with neutrophilia and monocytosis. Leukocyte ratios have been found to have prognostic value in humans and animals affected by a range of inflammatory, infectious, and neoplastic disorders. We hypothesized that in primary IMHA, neutrophil to lymphocyte (NLR), neutrophil to monocyte (NMR), band neutrophil to segmented neutrophil (BNR) and monocyte to lymphocyte (MLR) ratios would be higher in dogs that did not survive to discharge. Medical records of dogs diagnosed with IMHA at two veterinary teaching hospitals were retrospectively reviewed. Twenty-three of the 72 included dogs did not survive to discharge. NLR, NMR, BNR and MLR ratios were compared between dogs that survived to discharge and dogs that died or were euthanized. None of the ratios were significantly different between survivors and non-survivors (P = 0.14-0.99). Area under the Receiver Operating Characteristic (ROC) curve for prediction of non-survival ranged from 0.5 (95% confidence interval 0.38-0.62) for MLR to 0.61 (0.49-0.72) for NMR and was not significantly different from 0.5 for any ratio (P = 0.29-0.99). After exclusion of 31 dogs that received one or both immunosuppressive medications and blood transfusion before presentation, the area under the ROC curve for prediction of survival was significantly different from 0.5 for MLR (0.78, P = 0.01) and NMR (0.78, P = 0.0002). This study suggests that lower MLR and higher NMR may predict poorer prognosis in untreated dogs with IMHA.

Diagnostic imaging findings in a referral population of dogs diagnosed with immune-mediated haemolytic anaemia: 50 cases (2015-2018).

OBJECTIVES: To describe and characterise changes documented on thoracic and abdominal imaging of dogs with confirmed immune-mediated haemolytic anaemia. MATERIALS AND METHODS: Medical records from a referral hospital were searched from 2015 to 2018 for all dogs diagnosed with immune-mediated haemolytic anaemia that underwent thoracic and abdominal imaging by radiography, ultrasound or computed tomography. RESULTS: Fifty dogs were included. Thoracic imaging revealed abnormalities in 10 dogs (20%) of which lymphadenopathy and cardiomegaly were documented in four dogs (8%) each, and pleural effusion and pleural thickening in one dog (2%) each. Abdominal imaging revealed abnormalities in 43 dogs (86%), in which hepatomegaly and peritoneal effusion were documented in 20 (40%) and 19 dogs (38%), gallbladder wall thickening and sludge in 16 (32%) and 14 dogs (28%) and splenic nodules and splenomegaly in 13 (26%) and seven dogs (14%), respectively. Hepatic and splenic abnormalities were further investigated via fine needle aspirates in 18 dogs and revealed extramedullary haematopoiesis in 12 hepatic (66.7%) and 14 splenic (77.8%) fine needle aspirate samples. Cholecystocentesis was performed in nine dogs with gallbladder abnormalities and revealed bactibilia in three samples (33.3%). CLINICAL SIGNIFICANCE: In this population of dogs with immune-mediated haemolytic anaemia, thoracic imaging abnormalities were uncommon. Hepatomegaly, peritoneal effusion and gallbladder wall thickening were the most common abdominal imaging findings with bactibilia confirmed in one third of collected bile samples. Hepatosplenomegaly and abdominal lymphadenopathy were not associated with neoplasia in any of the dogs included in this study.

Effectiveness of aspirin vs. clopidogrel in dogs with immune mediated haemolytic anaemia evaluated by serial thromboelastography and platelet mapping.

Most dogs with immune mediated haemolytic anaemia (IMHA) are hypercoagulable, as measured by thromboelastography (TEG). Thromboelastography-platelet mapping (TEG-PM) has been used to assess platelet function in human patients treated with aspirin or clopidogrel. The aim of this study was to compare platelet thromboxane A2-receptor inhibition (TXA2-RI) and platelet adenosine diphosphate (ADP)-receptor inhibition (ADP-RI) as measured by TEG-PM in dogs with primary IMHA receiving aspirin or clopidogrel to determine if TEG-PM might be useful to monitor treatment. Eighteen client-owned dogs with IMHA were enroled in a prospective double blinded study. Dogs were randomised to receive aspirin or clopidogrel in addition to standard therapy. Thromboelastography was measured before, and 1 and 4 days after commencing treatment. Thromboelastography-PM was performed on days 1 and 4. Non-responders were defined as < 50 % platelet thromboxane A2-receptor inhibition (TXA2-RI) in the aspirin group and < 50 % platelet adenosine diphosphate (ADP)-receptor inhibition (ADP-RI) in the clopidogrel group, on day 4. Mean platelet TXA2-RI and platelet ADP-RI were not significantly different between groups at any timepoint (P > 0.05). The overall mean percentage inhibition of TXA2-receptor was 25 % (aspirin 33 %, clopidogrel 15 %), and of ADP-receptor was 82 % (aspirin 83 %, clopidogrel 80 %). On day 4, 6/9 dogs (66 %) in the aspirin group and 2/8 dogs (25 %) in the clopidogrel group were non-responders (P = 0.086). Two dogs defined as responders based on TEG-PM developed thromboembolism. Overall, there was no significant difference in efficacy between aspirin and clopidogrel based on measurement of receptor inhibition using TEG-PM (P > 0.05), and routine TEG was not reliable for monitoring treatment response in dogs with IMHA. In some dogs, there was a discrepancy between TEG-PM results and clinical response. Further investigation of TEG-PM use in dogs, including its usefulness to monitor treatment response and adjust treatment in individual dogs and any effect of anaemia, is warranted.

Centrifugal therapeutic plasma exchange in dogs with immune-mediated hemolytic anemia (2016-2018): 7 cases.

OBJECTIVE: To describe the technique of centrifugal therapeutic plasma exchange (cTPE) in dogs diagnosed with immune-mediated hemolytic anemia (IMHA) and summarize the outcome of the procedure. DESIGN: Retrospective review of cTPE performed at North Carolina State University from 2016 to 2018, through a search of the institutional database for cTPE and IMHA. SETTING: University teaching hospital. ANIMALS: Seven dogs with confirmed IMHA were presented to a university teaching hospital ICU for cTPE. Six dogs were not responsive to standard medical management with immunosuppressive agents, while 1 dog presented before immunosuppressive agents were begun. INTERVENTIONS: All dogs underwent multiple cTPE procedures using 1 of 2 commercially available apheresis systems. MEASUREMENTS AND MAIN RESULTS: At presentation, the median HCT was 0.15 L/L (15.7%) (range, 0.10-0.19 L/L [10.3%-19%]) and the median total serum bilirubin was 32.5 mmol/L (1.9 mg/dl) (range, 15.4-597 mmol/L [0.9-34.9 mg/dl]). The median number of transfusions before cTPE was 1 (range, 1-4), with a median total of infused RBCs of 12.9 ml/kg (range, 8.8-37 ml/kg). cTPE with an exchange of ≥4 times total plasma volumes was used to decrease the level of circulating autoreactive antibodies. The median total plasma volumes exchanged was 4.5 times (range, 2.5-6.5 times) over 2-4 procedures. Anticoagulation was performed using a combination of systemic heparinization and regional citrate in all dogs. Six of 7 dogs (85.7%) were discharged from the hospital and were alive 90 days after discharge. One dog (14%) did not respond to cTPE (∼6.5 times total plasma volume exchanged) and was euthanized. CONCLUSIONS: cTPE is a feasible and relatively safe bridging treatment option for the management of canine IMHA.

Treatment of a cat with presumed Bartonella henselae-associated immune-mediated hemolytic anemia, fever, and lymphadenitis.

A 2.5-year-old castrated male cat presented with fever and marked generalized lymphadenopathy of 4-months duration, despite treatment with amoxicillin-clavulanate/marbofloxacin. Abnormalities were not detected on complete blood count, serum chemistry, and FIV/FeLV test apart from a borderline, non-regenerative anemia. Peripheral lymph node fine needle aspirations revealed a marked increase in the percentage of intermediate- and lymphoblastic-lymphocytes in addition to reactive macrophages. Three weeks after presentation, the cat developed a severe, regenerative, immune-mediated hemolytic anemia (IMHA) which responded to immunosuppressive therapy. Fever and lymphadenopathy persisted. Peripheral lymph nodes tested positive for Bartonella henselae DNA in real-time PCR assay and sequencing. Treatment with pradofloxacin and doxycycline resulted in resolution of clinical signs, and negative PCR tests. Despite its reported low pathogenicity, B. henselae infection should also be considered in cats with protracted unexplained fever, lymphadenitis, and IMHA. Furthermore, a combination of pradofloxacin and doxycycline might be considered in cats with bartonellosis given its apparent clinical efficacy.

Presumptive hemophagocytic syndrome associated with immune-mediated anemia in two Miniature Dachshunds.

This report describes the cases of two Miniature Dachshunds who were suspected to have immune-mediated hemolytic anemia (IMHA) and were treated with immunosuppressive therapy. However, progression of anemia, increases in C-reactive protein (CRP) and total-bilirubin (T-Bil) levels, splenomegaly, transition to nonregenerative anemia, and thrombocytopenia occurred after the treatment. Splenectomy and bone-marrow aspirations were performed subsequently. Both dogs were diagnosed with hemophagocytic syndrome (HPS) associated with IMHA. Unfortunately, they died 9 and 6 days later. These findings indicate that some cases of refractory IMHA have the pathogenicity of HPS. HPS should be included as a differential diagnosis of refractory IMHA concurrent with thrombocytopenia. Continuously elevated CRP and T-Bil levels may be helpful indicators in the detection of HPS associated with IMHA.

Immune-mediated haemolytic anaemia and thrombocytopenia in 25 adult equids: 1997-2016.

BACKGROUND: Information concerning clinical presentation, conditions associated with immune-mediated haemolytic anaemia (IMHA) and thrombocytopenia (IMTP) and outcome in equids is lacking. Previous case reports suggest that immune-mediated disease and neoplasia are associated. OBJECTIVES: Characterise the clinical presentation, clinicopathologic data, underlying conditions, treatment and outcome of IMHA and IMTP cases in equids. We hypothesise that IMHA with concurrent thrombocytopenia occurs more often than IMHA or IMTP alone, and that neoplasia is commonly associated with these immune diseases and cases frequently have a poor prognosis. STUDY DESIGN: Retrospective case-control study. METHODS: Medical records were reviewed from 1997 to 2016. Twenty-five equids were diagnosed with IMHA, IMTP or IMHA with thrombocytopenia by Coombs test or flow cytometry. Controls were equids presented for nonimmune-mediated disease immediately prior to and after study animals. Fisher's exact test was used to compare between groups for categorical variables (P < .05). Results reported as odds ratios (OR) and 95% confidence intervals (CI). Unpaired t test and Mann-Whitney test were used to compare between groups for continuous variables (P < .05). RESULTS: Neoplasia incidence was significantly higher in the study population (28%) versus controls (8%) (P = .04). Equids with primary disease were more likely to survive to discharge than equids with secondary disease (8/9 vs 7/16; P = .03; OR = 13.3; 95% CI: 1.3-134.7). Survivors had a significantly lower blood urea nitrogen (BUN) than those that died or were subjected to euthanasia (survivors, 6.1 ± 2.5 mmol/L vs nonsurvivors, 9.9 ± 3.1 mmol/L P = .003). The odds of short-term mortality were higher in horses presenting with increased BUN (OR = 19.5; 95% CI, 1.8-214.1; P = .009). MAIN LIMITATIONS: Retrospective nature of the study, small case numbers and limited long-term follow-up. CONCLUSIONS: Primary IMHA/IMTP cases have a reasonable prognosis and warrant treatment. Secondary cases have a poor prognosis, and are frequently associated with cancer. BUN may have utility as a prognostic indicator for IMHA/IMTP cases.

ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats.

Immune-mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune-mediated erythrocyte destruction, and adverse consequences of long-term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence-based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.

Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

BACKGROUND: Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. OBJECTIVES: The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. METHODS: Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. RESULTS: Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. CONCLUSIONS: Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis.

Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs.

OBJECTIVES: To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. METHODS: Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. RESULTS: A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). CLINICAL SIGNIFICANCE: Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs.

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia.

BACKGROUND: Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated. AIMS: To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases. ANIMALS: 19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs. METHODS: Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset. RESULTS: There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response. CONCLUSIONS: The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA.

Novel immunotherapies for immune-mediated haemolytic anaemia in dogs and people.

Therapy of autoimmune diseases in dogs and people currently relies on use of broad-spectrum immunosuppressive drugs, which are associated with unacceptable adverse effects in some patients. Detractions of such drugs are particularly apparent in people and animals with autoimmune haemolytic anaemia (AIHA), when high doses are often required and for prolonged periods. Greater understanding of the immune aberrations that occur in patients with AIHA has permitted development of several forms of novel immunotherapy, which are intended to re-establish tolerance of self-antigens rather than suppressing all parts of the immune system. Such therapies should be efficacious while still permitting normal responses to pathogens and inoculation. Immunotherapies of particular interest currently include monoclonal antibodies that produce selective depletion of the B cell compartment to decrease autoantibody production, administration of peptide antigens by subcutaneous or sublingual routes to establish tolerance, adoptive transfer of regulatory T cells (Tregs), and administration of low dose recombinant interleukin 2 to encourage proliferation and activation of Tregs. These therapies are in variable stages of development, with some being trialled in people and client-owned dogs, and others undergoing validation in experimental murine models. Continued development of these immunotherapies is likely to lead to the introduction of several novel products for the management of autoimmune disease in veterinary practice in the future.

The use of the rapid osmotic fragility test as an additional test to diagnose canine immune-mediated haemolytic anaemia.

BACKGROUND: Diagnosing canine immune-mediated haemolytic anaemia (IMHA) is often challenging because all currently available tests have their limitations. Dogs with IMHA often have an increased erythrocyte osmotic fragility (OF), a characteristic that is sometimes used in the diagnosis of IMHA. Since the classic osmotic fragility test (COFT) is time-consuming and requires specialized equipment, an easy and less labour-intensive rapid osmotic fragility test (ROFT) has been used in some countries, but its diagnostic value has not yet been investigated.This study aimed to evaluate erythrocyte osmotic fragility in dogs with and without IMHA, to compare results of the classic (COFT) and rapid (ROFT) test and to assess the value of the ROFT as diagnostic test for canine IMHA.Nineteen dogs with IMHA (group 1a), 21 anaemic dogs without IMHA (group 1b), 8 dogs with microcytosis (group 2), 13 hyperlipemic dogs (group 3), 10 dogs with lymphoma (group 4), 8 dogs with an infection (group 5) and 13 healthy dogs (group 6) were included.In all dogs, blood smear examination, in-saline auto-agglutination test, Coombs' test, COFT and ROFT were performed. In the COFT, OF5, OF50 and OF90 were defined as the NaCl concentrations at which respectively 5, 50 and 90% of erythrocytes were haemolysed. RESULTS: Compared with healthy dogs, OF5 and OF50 were significantly higher in group 1a (P < 0.001) and OF5 was significantly higher in group 3 (P = 0.0266). The ROFT was positive in 17 dogs with IMHA, 10 hyperlipemic dogs, one anaemic dog without IMHA and one healthy dog. CONCLUSIONS: Osmotic fragility was increased in the majority of dogs with IMHA and in dogs with hyperlipidemia, but not in dogs with microcytosis, lymphoma or an infection. Although more detailed information was obtained about the osmotic fragility by using the COFT, the COFT and ROFT gave similar results. The ROFT does not require specialized equipment, is rapid and easy to perform and can be used easily in daily practice. Although, the ROFT cannot replace other diagnostic tests, it may be a valuable additional tool to diagnose canine IMHA.

NT-ProBNP and cardiac troponin I in virulent canine babesiosis.

Although cardiac pathology and consequently elevated serum cardiac troponin I (cTnI) have been reported, clinically it remains difficult to diagnose cardiac involvement in canine babesiosis. Thus the use of cardiac biomarkers would be useful in determining if a dog with babesiosis also has concurrent cardiac dysfunction. The objectives of this study were to determine plasma N terminal brain natriuretic peptide (NT-proBNP) in canine babesiosis and if it is correlated with cTnI. Three groups of dogs with babesiosis were used: mild uncomplicated (Group 1), severe uncomplicated (Group 2), and complicated (Group 3), and a control group (Group 4) with 15 dogs per group. Each animal had the following determined: serum urea and creatinine, urea: creatinine ratio, cystatin-C, cTnI, blood lactate, plasma NT-proBNP, fractional shortening (FS), and blood pressure. The median NT-proBNP value in Groups 1-4 was 246, 650, 638, and 106 pmol/l. All 3 babesiosis groups had a statistically elevated NT-proBNP level compared to the control group and Groups 2 and 3 showed significantly higher values compared to Group 1. Median cTnI in Group 1-3 was 0.39, 0.4, and 1.45 ng/ml, respectively with the control group having concentrations below the detection limit (0.2 ng/ml). There was a significant difference in cTnI concentration between the control group and group 3 but no statistical difference between the other babesiosis groups. The study concluded that dogs with babesiosis showed elevated levels NT-proBNP and the more severe the disease process the greater the elevation. This elevation is earlier or independent of the increased cTnI.

Lack of evidence of a beneficial effect of azathioprine in dogs treated with prednisolone for idiopathic immune-mediated hemolytic anemia: a retrospective cohort study.

BACKGROUND: Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA treated with a protocol that included azathioprine and prednisolone versus a protocol that included prednisolone alone. RESULTS: The study included 222 dogs with a hematocrit lower than 0.30 L/L and either a positive Coombs' test or spherocytosis and no evidence of diseases that could trigger IMHA. The clinical and laboratory data at the time of diagnosis and the response to therapy and survival were compared in dogs treated according to the prednisolone and azathioprine protocol (AP protocol; n = 149) and dogs treated according to the prednisolone protocol (P protocol; n = 73). At study entry, the two groups were comparable, except that thrombocyte counts were significantly lower and clinical signs had been present significantly longer in the AP protocol group. No significant difference in survival was found between the two groups: the 1-year survival was 64% (95% CI 54 - 77%) in the P protocol group and 69% (95% CI 59-80%) in the AP protocol group, respectively. CONCLUSIONS: Azathioprine would appear not to be beneficial as standard treatment for all cases of IMHA; however, a blinded, randomized clinical trial is needed to establish whether outcome is different with the two treatment protocols.

The effects of deferoxamine mesylate on iron elimination after blood transfusion in neonatal foals.

BACKGROUND: Hepatic failure is one of the more common complications in foals requiring blood transfusion to treat neonatal isoerythrolysis. Iron intoxication is likely the cause of hepatic injury. OBJECTIVES: To determine the effects of deferoxamine on iron elimination in normal foals. ANIMALS: Thirteen neonatal foals. METHODS: Randomized-controlled trial. At 1-3 days of age, foals received either 3 L of washed packed dam's red blood cells (RBC) or 3 L of saline IV once. Foals were treated with deferoxamine (1 g) or saline (5 mL) SC twice daily for 14 days. Foals were randomly assigned to 1 of 3 groups: RBC/deferoxamine (deferoxamine), RBC/saline (placebo), or saline/saline (control). Blood and urine samples and liver biopsy specimens were collected for measurement of hematological, biochemical, and iron metabolism variables. RESULTS: There was a significant (P<.05) increase in hematocrit, RBC count, and hemoglobin in the groups transfused with packed RBC as compared with controls at all times. Biochemical variables and liver biopsy scores were not significantly different between groups at any time. Urine iron concentrations and fractional excretion of iron were significantly higher in deferoxamine treated foals. By 14 days after transfusion, liver iron concentrations in foals treated with deferoxamine (79.9±30.9 ppm) were significantly lower than that of foals receiving placebo (145±53.0 ppm) and similar to that of controls (44.8±4.09 ppm). CONCLUSIONS AND CLINICAL IMPORTANCE: Deferoxamine enhances urinary iron elimination and decreases hepatic iron accumulation after blood transfusion in foals.

Evaluation of serum ferritin as a tumor marker for canine histiocytic sarcoma.

BACKGROUND: Canine histiocytic sarcoma (HS) is an aggressive malignancy. Hyperferritinemia has been documented in dogs with HS and could serve as a tumor marker aiding in diagnosis and treatment. In people, hyperferritinemia is found in inflammatory diseases, liver disease, and hemolysis, and thus may occur in dogs with these conditions. OBJECTIVE: To determine if serum ferritin concentration is a tumor marker for canine HS. ANIMALS: Dogs with HS (18), inflammatory diseases (20), liver disease (24), immune-mediated hemolytic anemia (IMHA) (15), and lymphoma (23). METHODS: Prospective, observational, cohort study: Serum ferritin concentration was measured at initial diagnosis. Parametric methods were used to compare mean log ferritin concentrations among disease categories. Receiver-operating characteristic curves and likelihood ratios were used to evaluate serum ferritin concentration as a tumor marker. RESULTS: Varying proportions of dogs with IMHA (94%), HS (89%), liver disease (79%), lymphoma (65%), and inflammatory diseases (40%) had hyperferritinemia. Dogs with IMHA had significantly higher mean ferritin concentration than dogs in all other categories. Dogs with HS had significantly higher mean ferritin concentration than those in the inflammatory disease and lymphoma categories. Mean serum ferritin concentration was not significantly different between dogs with HS and those with liver disease. Decision thresholds were determined to distinguish IMHA and HS from the other diseases associated with hyperferritinemia. CONCLUSION: Hyperferritinemia is common in dogs with HS and, after IMHA is ruled out, the degree of hyperferritinemia may be useful in differentiating dogs with HS from dogs with inflammatory diseases, liver disease, and lymphoma.

Coombs', haemoplasma and retrovirus testing in feline anaemia.

OBJECTIVE: To investigate the associations between Coombs' testing, haemoplasma and retroviral infections, and feline anaemia. METHODS: Haematology, Coombs' testing (including assessment of persistent autoagglutination) and selected infection testing (haemoplasma, feline leukaemia virus/feline immunodeficiency virus provirus) were performed in blood samples collected from 60 anaemic and 60 non-anaemic cats. RESULTS: No association between infection and anaemia or Coombs' positivity existed. Anaemic cats (21.7%) were significantly more likely than non-anaemic cats (0%) to have cold autoagglutination (P<0.0001), but significance (set at