Diseases Associated With Increased Erythrocyte Destruction (Hemolytic Anemia)
Johanna L. Watson • Gary P. Carlson
Hemolytic disorders are characterized by an increased rate of red cell destruction, and anemia results when the rate of red cell destruction exceeds the bone marrow capacity for increased proliferative response.
Although intravascular hemolysis occurs in some circumstances, these anemias are primarily due to an increased rate of extravascular erythrocyte destruction and shortened intravascular life span.Hemolytic anemias are associated with a wide range of systemic disease processes. A list of differential considerations for possible causal factors of hemolytic anemia in large animals is presented in Box 37.1. Clinical manifestations of hemolytic anemia will vary with the degree of anemia, rate of red cell destruction, and primary or underlying disease process. However, several common clinical signs are seen in animals with severe hemolytic anemia, regardless of the cause: mucous membrane pallor, fatigue, depression, and anorexia. Clinical icterus can be quite variable depending on the rate of red cell destruction and the liver's ability to excrete bilirubin. Icterus is a characteristic feature in hemolytic anemia, but intense icterus is noted only after massive red cell destruction and is often transient. With continued low-level hemolytic processes, the liver may be able to excrete bilirubin at a rate sufficient to avoid clinical icterus. Hemolytic icterus must be differentiated from other potential causes like liver disease or anorexia in horses. If icterus is caused by hemolytic processes, clear clinical and hematologic evidence of anemia should exist. Massive intravascular hemolysis may result in an orange to reddish discoloration of the mucous membranes. Modest to marked and often variable febrile responses are frequently encountered in hemolytic anemias caused by infectious agents and during periods of active erythrocyte destruction.
With advanced anemia the pulse and respiratory rates are elevated at rest. Death losses may occur, and neurologic abnormalities ranging from bizarre behavior to mania, collapse, and death may be associated with handling animals with severe anemia.The hematologic manifestations of hemolytic anemia also vary with the rate of red cell destruction, time course of the anemia, and primary or underlying disease process. Anemia may be modest to severe, and after the first few days
■ BOX 37.1
Causes of Hemolytic Anemia
Infectious Causes
Parasitic
Anaplasmosis
Babesiosis
Hemobartonellosis
Eperythrozoonosis
Theileriasis
Trypanosomiasis
Bacterial
Leptospirosis
Bacillary hemoglobinuria
Viral
Equine infectious anemia (EIA)
Immune-Mediated Hemolytic Anemia
Autoimmune hemolytic anemia
Neonatal isoerythrolysis (NI)
Drug induced: penicillin, trimethoprim-sulfamethoxazole
Heinz Body Hemolytic Anemia
Phenothiazine toxicity
Wild onion poisoning
Red maple leaf poisoning
Other Causes
Severe cutaneous burns
L-Tryptophan-indole intoxication
Water intoxication
Postparturient hemoglobinuria
Copper poisoning
Hemolytic syndrome in horses with liver failure Erythropoietic porphyria in Holstein cattle
in all species except the horse, there is usually hematologic evidence of enhanced erythropoietic response seen as increased anisocytosis, polychromasia, reticulocytosis, and the presence of nucleated red blood cells in the circulation. Morphologic abnormalities of diagnostic significance (e.g., intracellular or epicellular parasites, granulocytic inclusion bodies, Heinz bodies, spherocytes, schistocytes, or poikilocytes) may be noted on examination of stained blood smears. Responsive anemias often are accompanied by neutrophilia and a regenerative left shift. Bone marrow usually shows an active erythropoietic response with a decreased myeloid/erythroid (M:E) ratio. The serum concentration of haptoglobin is decreased, and serum lactate dehydrogenase enzyme activity may be elevated during acute hemolytic episodes. An increase in serum bilirubin concentration caused primarily by an increase in indirect reacting bilirubin is a reflection of active red cell destruction. Specific serologic diagnostic procedures are available for many of the infectious causes of hemolytic anemia. Immunohematologic procedures like the direct and indirect Coombs test provide an indication that immune-mediated processes contribute to enhanced erythrocyte destruction. It should be noted that the principal mechanisms responsible for the increased rate of red cell destruction associated with many infectious causes of hemolytic anemia (parasitic, bacterial, viral) are immunologically mediated, and affected animals may be transiently Coombs positive.
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