Immune-mediated hemolytic anemia in a horse

An 18-year-old Quarter Horse gelding was determined to have immune-mediated hemolytic anemia after detection of autoagglutination of RBC spherocytosis as well as a positive direct Coombs test result. A lack of response to treatment with corticosteroids necessiated the administration of cyclophosphamide and azathioprine. The anemia resolved after treatment with chemotherapeutic drugs.     

Immune-mediated hemolytic anemia in an eclectus parrot

CASE DESCRIPTION: A 2-year-old female Solomon Island eclectus parrot (Eclectus roratus) was evaluated by a veterinarian because of a 4-day history of progressive lethargy, weakness, poor appetite, and inactivity. The bird was referred to a veterinary teaching hospital for further examination. CLINICAL FINDINGS: Clinicopathologic analyses revealed that the parrot had marked regenerative anemia, autoagglutination, and biliverdinuria. Small, rounded RBCs (thought to be spherocytes) were detected in blood smears. The abnormal findings met the diagnostic criteria for dogs with primary immune-mediated hemolytic anemia. However, analyses of blood samples for lead and zinc concentrations and plasma bile acids concentrations; the use of PCR assays for Chlamydophila psittaci, psittacine circovirus 1 (causative agent of beak and feather disease), and polyomavirus; and microbial culture and Gram staining of feces did not reveal a cause for the hemolytic anemia. TREATMENT AND OUTCOME: Although administration of immunosuppressive doses of cyclosporine was initiated, there was a rapid progression of disease, which lead to death of the parrot before this treatment could be continued long-term. Lack of an identifiable underlying disease (confirmed by complete histologic examinations at necropsy) supported the diagnosis of primary immune-mediated hemolytic anemia. CLINICAL RELEVANCE: Primary immune-mediated hemolytic anemia has not been widely reported in psittacine birds. A comprehensive evaluation and complete histologic examination of tissues to rule out underlying disease processes are required to definitively establish a diagnosis of primary immune-mediated hemolytic anemia in parrots. Primary immune-me-diated hemolytic anemia should be considered as a differential diagnosis for regenerative anemia in a parrot.     

Immune-mediated hemolytic anemia and thrombocytopenia in a foal

A one-month-old Quarter Horse filly had unilateral epistaxis, hyphema, icterus, petechial hemorrhages in the oral, nasal, conjunctival, and vulvar mucous membranes, anemia, thrombocytopenia, negative antinuclear test result, and a positive direct Coombs' test result. Megakaryocytes or cell-associated IgG (fluorescent antibody and immunoperoxidase stains) were not found in bone marrow biopsy specimens. Treatment consisted of glucocorticoids, antibiotics, and a single whole blood transfusion. The foal responded well to treatment, did not develop relapses of the disease, and was clinically normal one year after treatment.     

Immune-mediated hemolytic anemia: understanding the nemesis.

IMHA is one of the most common causes of anemia in small animals. Although treatment may be rewarding, many patients do not respond adequately to glucocorticoids alone and require additional immunosuppressive therapy. Some patients may succumb to acute severe anemia and die within the first few weeks of treatment; even if they survive, relapses may occur. IMHA is the nemesis; as our understanding of this disease increases and treatment options expand, it is hoped that survival rates will finally improve.     

Immune-mediated hemolytic anemia associated with trimethoprim-sulphamethoxazole administration in a horse.

A 10-year-old, thoroughbred gelding was administered sulphonamide drugs during surgical treatment of guttural pouch mycosis. The horse became anemic and a diagnosis of immune-mediated hemolytic anemia was made after other causes of anemia had been ruled out. The anemia resolved after the drugs were withdrawn.     

Immune-mediated hemolytic anemia: 70 cases (1988-1996).

Survival times and mortality rates in dogs with idiopathic immune-mediated hemolytic anemia (IMHA) have been infrequently reported in the literature. This study evaluates survival and mortality in a large group of dogs with IMHA. The association of age, sex, and breed with IMHA was evaluated by comparing affected dogs to control dogs admitted to the hospital during the same time period. Treatment regimens were reviewed to determine the effects of different agents upon survival of dogs with IMHA during hospitalization and after discharge. Median survival times for each treatment group were 57 days (prednisone), 28 days (prednisone, cyclophosphamide), 974 days (prednisone, azathioprine), 15 days (prednisone, cyclophosphamide, azathioprine), and one day (no treatment). Overall mortality rate in the population of dogs studied was 70%. Twenty-nine (41.4%) dogs either died or were euthanized while hospitalized. Forty-one (59%) dogs were discharged from the hospital. Of the dogs discharged, 10 died within the first month, another five died within three months, and another five died within a year of discharge due to assumed complications of therapy or relapses of IMHA.     

Isotype-specific antibodies in horses and dogs with immune-mediated hemolytic anemia

Classes of antibody bound to erythrocytes were determined using direct immunofluorescence (DIF) flow cytometry in 3 horses and 12 dogs with immune-mediated hemolytic anemia (IMHA). Background levels of antibody binding were determined in samples from 12 horses and 12 dogs that were free of clinical disease. The range of nonspecific binding of a fluorescein isothiocyanate (FITC)-conjugated goat anti-equine immunoglobulin G (IgG) was 19.9–36.7%, but was eliminated by the use of the F(ab)₂ fragment of FITC-conjugated goat anti-equine IgG. Background binding by other class-specific antibodies to equine and canine erythrocytes was negligible. The DIF results were compared to the direct antiglobulin (Coombs) test in 5 horses and 20 dogs with anemia. The former assay was more sensitive in dogs with IMHA than was the Coombs' test (100% versus 58%). In contrast, the Coombs' test had better specificity than the DIF assay (100% versus 87.5%, respectively). Using clinical parameters or response to therapy as the comparison, the positive and negative predictive values for the DIF test were 92% and 100% compared to the values of the Coombs' test of 100% and 62%. The DIF assay detected low levels of cells bound with antibody (<30%) in 5 dogs that were Coombs' test-negative. For both species, performance of the DIF test was independent of the prozone effect. Five dogs with IMHA had IgG and IgM on erythrocytes, 5 had IgG, and 2 had IgM. Three horses had surface-bound IgG, including a horse with suspected penicillin-induced IMHA, a foal with neonatal isoerythrolysis, and a foal with clostridial septicemia. The DIF method was valuable in monitoring the response to therapy in the foal with neonatal isoerythrolysis.     

Lymphosarcoma and associated immune-mediated hemolytic anemia and thrombocytopenia in horses

Three horses with equine lymphosarcoma were examined because of clinical signs including chronic weight loss, respiratory distress, peripheral edema, and chronic colic. Clinicopathologic findings included evidence of an immune-mediated hemolytic anemia. Immune-mediated thrombocytopenia also was diagnosed in 1 of the horses and suspected in another. One horse died in spite of treatment, 1 died 5 hours after surgical removal of a tumor encircling the jejunum, and 1 was euthanatized because of deteriorating condition. Necropsy of each horse revealed extensive neoplastic infiltration of peripheral lymph nodes and abdominal or thoracic viscera with neoplastic lymphocytes.     

Acute hemolytic anemia induced by oral administration of indole in ponies

Eight ponies were allotted to 2 groups of 4. Group-1 ponies (1-4) were given 0.2 g of indole/kg of body weight orally and group-2 ponies (5 to 8) were given 0.1 g of indole/kg. Various physical, hematologic, and physiologic measurements were obtained after administration of indole. Intravascular hemolysis and hemoglobinuria were detected in both groups within 24 hours of dosing. Hemolysis was reflected by decreases in PCV, hemoglobin concentration, and RBC count, and an increase in indirect bilirubin. Erythrocyte fragility appeared to increase in both groups at 8 hours after dosing and peaked at 16 hours after dosing. At 72 hours after dosing, the RBC fragility value was less than predose measurements. Heinz body formation was noticed in group-2 ponies, but not in group 1. Plasma indole concentrations increased in both groups from the nondetectable predose concentrations. Group-1 values were 203% of group-2 values. In group 2, plasma indole was nondetectable by 12 hours, whereas low concentrations could still be measured in the group-1 ponies at 24 hours. Ponies in group 1 died or were euthanatized between 24 and 72 hours after dosing, whereas group-2 ponies were euthanatized between 48 and 120 hours. At necropsy, all body fat, mucous membranes, and elastic tissue were stained yellow. Hemoglobinuric nephrosis was the most prominent microscopic lesion. Results of this study indicated that indole, a metabolite of the amino acid tryptophan, causes acute intravascular hemolysis in ponies.     

Erythrocyte volume distribution analysis and hematologic changes in two horses with immune-mediated hemolytic anemia

Immune-mediated hemolytic anemia was diagnosed in two horses on the basis of regenerative anemia, increased erythrocyte fragility in hypotonic saline, autoagglutination, and a positive direct antiglobulin (Coomb's) test. During steroid therapy partial resolution of the anemia was indicated by rising packed cell volume, macrocytosis, and bone marrow erythroid hyperplasia. Using erythrocyte volume distribution histograms (erythrograms), the regenerative response was characterized by analysis of macrocytic and normocytic erythrocyte subpopulations. In both horses, a gradual net increase of about 2 X 10(6) macrocytes/microliter occurred over a four- to five-week period. Over the same interval there was a gradual decrease in the number of normocytes. We suggest that the macrocytes remained large through this period rather than contributing to normocyte population growth. Erythrograms may provide an additional means of evaluating erythrocyte regeneration in horses.     

Hereditary nonspherocytic hemolytic anemia in beagles

Three Beagles with chronic anemia and reticulocytosis were studied. The dogs originated from a large breeding colony and appeared clinically normal with the exception of splenomegaly. The PCV ranged from 30 to 39% (normal, 46 to 56%), with reticulocyte indices of 2.3 to 9.9. Red blood cells were morphologically normal, and examination of marrow aspirates revealed erythroid hyperplasia. Shortened chromium-51 RBC life-spans (7.2 to 15.4 days in anemic dogs; 22.2 to 25.2 days in control dogs) documented a hemolytic anemia. Acquired causes of hemolytic anemia were ruled out. Red blood cells had normal glycolytic enzyme activities, no evidence of unstable or abnormal hemoglobin, and had altered osmotic fragility curves. The breeding of 2 anemic dogs resulted in offspring with anemia and reticulocytosis. Polyacrylamide gel electrophoresis revealed no abnormalities in RBC membrane cytoskeletal proteins in all anemic adult dogs and in 3 offspring.     

Experimental onion-induced hemolytic anemia in dogs

Within one day following a single oral dose of dehydrated onions, dogs were found to have large numbers of Heinz bodies within erythrocytes. The percentage of erythrocytes that contained Heinz bodies increased slightly to a maximum on day 3 and then declined. The turbidity index increased more gradually with a maximal value on day 4. Erythrocytes with hemoglobin contracted to one side of the cell (eccentrocytes) also appeared after onion feeding. Eccentrocytes are believed to result from a direct injury to the erythrocyte membrane. As with Heinz body-containing cells, the percentages of eccentrocytes present declined as anemia developed. The packed cell volume began to decrease one day after onion administration. A mean decrease of 19 percentage points was reached by day 5. The most anemic dogs had evidence of intravascular hemolysis. Reticulocytosis was first observed five days after onion administration. A slight increase in methemoglobin content was measured four hours after onion administration. No significant changes in erythrocyte reduced glutathione concentration were measured. Transient neutrophilia occurred concomitant with the peak reticulocyte response.     

Zinc-induced hemolytic anemia in a dog

A dog ingested a zinc nut that was retained in the stomach and caused a life-threatening hemolytic crisis with renal, gastrointestinal, and hepatic dysfunction. The dog was stabilized by blood transfusion and was anesthetized, and the zinc nut was removed with a fiberoptic endoscope. With continued supportive care, the dog recovered. Metallic zinc is found in high concentrations in nuts, bolts, and pennies. Zinc toxicosis should be considered in cases of unexplained hemolytic anemia.     

Familial nonspherocytic hemolytic anemia in poodles

Nonspherocytic hemolytic anemia, characterized by marked reticulocytosis, hepatosplenomegaly, hemosiderosis of reticuloendothelial organs and bone marrow myelofibrosis, and osteosclerosis, was diagnosed in 5 related Poodles. The unremitting anemia was clinically evident by 1 year of age, and was fatal as early as 3 years of age. Despite intense diagnostic endeavors including RBC fragility studies, RBC enzyme assays, and hemoglobin electrophoresis, the cause of this nonspherocytic hemolytic anemia remains to be determined.