Aplastic Anemia
Johanna L. Watson • Debra Deem Morris
Aplastic anemia is a stem cell disorder characterized by reduced marrow production of all blood components in the absence of a primary disease process infiltrating the bone marrow or suppressing hematopoiesis.18,19 Peripheral pancytopenia secondary to marrow aplasia is apparently uncommon in horses, although idiopathic hypoplastic anemia has been reported,20-22 as well as rare cases associated with phenylbutazone use.15-23 Hemorrhagic diathesis caused by thrombocytopenia is often the first indication of disease, manifested by epistaxis, mucosal petechiae, or prolonged hemorrhage after trauma or injections.
Pallor may be present, with other signs of anemia (e.g., reduced exercise tolerance) depending on the severity and rapidity of aplasia progression. Neutropenia causes increased susceptibility to infections, which may result in intermittent fever or weight loss. Lymphocyte production is reportedly not impaired, but absolute lymphopenia is common in aplastic anemia. Circulating lymphocytes are often highly reactive, producing the suspicion of neoplasia or a preleukemic syndrome.15The diagnosis of aplastic anemia is based on the combination of peripheral pancytopenia and bone marrow hypoplasia with fatty replacement. Because the normal erythrocyte life span in horses is roughly 140 days and in cattle exceeds 160 days,24 neutropenia with no left shift and thrombocytopenia are earlier hematologic manifestations.
The major aims in treatment of aplastic anemia are to remove the animal from suspected causative agents and provide supportive care, in the hope spontaneous remission will occur. Broad-spectrum antimicrobials are necessary to control infections. Blood transfusions are rarely indicated, and platelet transfusion should be reserved for severe bleeding episodes, which rarely occur.
Bone marrow transplantation is used with some success in humans, although graft-versus-host disease poses significant risk. The latter would presumably limit this therapy in horses; too few horses with aplastic anemia have been studied to give a clear indication of prognosis.Bracken fern toxicosis in ruminants causes bone marrow depression and subsequent pancytopenia.24 The toxic effects of the plant are cumulative, and clinical signs occur suddenly 2 to 8 weeks after cattle gain access to the plant. Clinical signs include fever, melena, epistaxis, hematuria, mucosal petechiae, hyphema, and bleeding from the eyes and vagina. Hematology reveals a platelet count less than 40,000^L and profound leukopenia with essentially no neutrophils present. Death may follow in 1 to 3 days as a result of the combined effects of multiple internal hemorrhages and bacteremia. The major toxic factor in bracken fern is thought to be ptaquiloside.24 Necropsy of cattle with bracken fern toxicosis reveals multiple hemorrhages throughout most tissues, necrotic GI tract ulcers, and pale bone marrow. Antibiotics and blood and platelet transfusions may be appropriate, but cattle with advanced bracken fern toxicosis (platelet count are most susceptible to the effects of high altitude, and some develop polycythemia at 1800 m above sea level. Horses develop an increased erythrocyte mass above 2200 m, especially when in training. Sheep are similar to cattle, but goats are apparently least susceptible to elevation hypoxia.
Congenital cardiac disorders that produce right-to-left shunts are a common cause for absolute erythrocytosis in large animals. Tetralogy of Fallot is the most common defect to cause shunting of unoxygenated blood into the peripheral circulation, although a number of other defects (ventricular septal defect [VSD] being the most common) may eventually result in right-to-left shunting and secondary erythrocytosis.4
Chronic impairment of alveolar ventilation may eventually cause erythrocytosis, although most chronic pulmonic diseases in large animals are not associated with significant hypoxemia.
Equine asthma (RAO, COPD) may produce enough ventilation/ perfusion mismatching to reduce the pressure of arterial oxygen below normal, but the resultant hypoxemia is insufficient to induce erythrocytosis.PHYSIOLOGICALLY INAPPROPRIATE ERYTHROCYTOSIS. Inappropriate elaboration of erythropoietin (i.e., normal PO2 and secondary erythrocytosis) may rarely accompany renal, hepatic, or endocrine disorders, especially those caused by neoplasia. Secondary erythrocytosis may accompany nonma- lignant renal disorders, in which local intrarenal ischemia is believed to mediate increased erythropoietin production. Paraneoplastic erythrocytosis with normal serum erythropoietin is due to tumor production of androgenic steroids or a protein with erythropoietin-like action.5 Increased plasma erythropoietin and secondary erythrocytosis has been identified in horses with hepatocellular carcinoma.3,6 Erythrocytosis was described in a horse with hepatoblastoma7,8 and in another with lymphoma,9 but serum erythropoietin levels as measured by a human assay were normal in both instances. In the horse with lymphoma, erythropoietin gene expression was identified in the lymphoma tissue. Typically, the diagnosis of inappropriate secondary erythrocytosis is based on elevated serum erythropoietin in the absence of hypoxemia. Elevated serum erythropoietin may not be demonstrated because of the nature of the assay or other compounds causing erythrocytosis.
Treatment of Erythrocytosis
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