Aplastic anemia results from congenital or acquired developmental failure of hematopoietic progenitor cells in the bone marrow. In other species, acquired aplastic anemia has been associated with bacterial and viral infections, chronic renal or hepatic failure, irradiation therapy, and drug administration, but the majority of cases are considered idiopathic. Until recently, aplastic anemia had only been reported in a few horses. No definitive cause was identified, although one horse had a positive Coombs test, thus suggesting an immune-mediated process. Phenylbutazone was implicated in two other cases. In the 1990s the advent of unapproved administration of a human recombinant erythropoietin to racehorses resulted in the emergence of a drug-induced immune-mediated anemia characterized by potentially fatal bone marrow erythroid suppression.
Endogenous erythropoietin, produced by the liver and activated in the kidney, stimulates red blood cell production by the bone marrow, thereby regulating maintenance of a normal peripheral red blood cell count. In an attempt to enhance performance by increasing circulating red cell mass, recombinant human erythropoietin (Epogen) has been administered to healthy racehorses. The recombinant product induces the production of antierythropoietin antibodies that cross-react with the horse’s endogenous erythropoietin. Endogenous erythropoietin thus is inactivated, and bone marrow red cell production is depressed. Complete shutdown of red cell production that results in fatal aplastic anemia has been reported in horses that were administered repeated doses of human recombinant erythropoietin. Local racing commissions should be contacted concerning any suspected case.
Clinical Signs, Diagnosis, and Treatment
Horses with advanced anemia caused by bone marrow hypoplasia show nonspecific clinical signs such as poor performance and weight loss as well as pale mucous membranes. Definitive diagnosis of aplastic anemia is based on bone marrow assessment. In two horses with erythroid hypoplasia and anemia after administration of recombinant human erythropoietin, bone marrow myeloid/erythroid ratios were 6.7 and 3.2 (normal 0.5-1.5), thus indicating severe, nonregenerative anemia. These horses also had increased serum iron concentrations, normal total iron binding capacities, and increased serum ferritin concentrations. Recombinant human erythropoietin can be detected in the plasma of horses for only 72 hours after dosing. Use of recombinant human erythropoietin can be suspected in horses if anti-EPO antibodies are detected in the patient’s serum or if endogenous erythropoietin levels are abnormally low (EPO Trac RIA, Incstar, Stillwater, Minn.).
In addition to aplastic anemia, pancellular bone marrow destruction secondary to neoplastic infiltration or myelofibrosis has been reported in the horse. In such cases, clinical signs are associated with loss of the shorter-lived cells, neutrophils, and platelets. Therefore fever, localized infection, and thrombocytopenic hemorrhage can be anticipated.
Treatment of aplastic anemia is focused on identification of underlying cause and on corticosteroid administration. Steroids stimulate erythropoiesis by increasing erythropoietin production and the sensitivity of stem cells to this hormone’s action. One horse with idiopathic aplastic anemia improved after administration of nandrolone decanoate (Deca-Durabolin), an anabolic steroid, and corticosteroids, and two horses with human recombinant erythropoietin-induced anemia recovered after drug withdrawal and administration of corticosteroids.
No successful treatment currently is available for myelophthisic diseases associated with pancytopenia.