Immune-mediated hemolytic anemia (IMHA) is a devastating disease in dogs with a reported mortality rate that ranges between
29% and 70% in the veterinary literature. Hemolysis results from the binding of immunoglobulins to red blood cell surface
antigens, causing those cells to be lysed by complement intravascularly or removed from circulation by mononuclear phagocytes.
IMHA may be a particularly frustrating disease for both owners and clinicians because of its waxing and waning clinical course,
the potential for sudden complications, and the expense associated with treatment.
Immune-mediated red blood cell destruction may be classified in a number of ways. Primary or idiopathic autoimmune hemolytic
anemia (AIHA) refers to immune-mediated hemolysis in the absence of an identifiable trigger factor, whereas secondary IMHA
results from an underlying process such as neoplasia, infectious disease, or drug reaction. IMHA may also be categorized based
on whether it results in intravascular or extravascular hemolysis. Intravascular hemolysis results from the lysis of red blood
cells by complement within the vasculature, and may be identified by the presence of free hemoglobin within the plasma and
urine. Extravascular hemolysis results when there are insufficient antibodies present to cause complement fixation, and antibody-labeled
red blood cells are removed by the reticuloendothelial system within the spleen and liver. Extravascular hemolysis tends to
be a more gradual process and may be identified by the presence of bilirubin (rather than hemoglobin) within the plasma and
urine. IMHA may also be classified based on the presence or absence of autoagglutination. Autoagglutination is the spontaneous
clumping of red blood cells and results from the cross-linking of erythrocytes by large numbers of antibodies.
IMHA is typically a disease of middle-aged to older pets. As with other types of immune mediated disease, a female gender
predisposition has been reported. At Michigan State University in the four years, approximately 2/3 of IMHA cases were seen
in spayed female dogs. Although any breed may develop IMHA, a number of breed predispositions have also been reported and
include Cocker Spaniels, Poodles, Shih Tzus, Lhasas, Old English Sheepdogs, Border Collies, and Springer Spaniels. A seasonal
predilection has also been suspected, as some studies have observed a larger number of cases presenting in spring and summer
months. This may be a result of increased exposure to outdoor allergens or antigenic stimulation, or may simply reflect the
overall increase in patient admissions seen during these months.
Clinical signs of IMHA may be acute or chronic, depending upon the rate of hemolysis. With chronic disease, symptoms such
as lethargy, weakness, inappetance, vomiting, diarrhea, and pigmenturia are most commonly reported, whereas with more rapid
hemolysis, acute collapse may be the first symptom noted. It is not uncommon for dogs to be brought in for "possible urinary
tract infection" because the owners have noted discoloration of the urine with hemoglobin or bilirubin. Symptoms related to
anemia, including tachycardia, tachypnea, and systolic ejection murmurs may also be noted on physical exam. Hepatosplenomegaly
is not unusual as these organs are common sites for extramedullary hematopoiesis as well as clearance of antibody-labeled
erythrocytes. Fevers are frequently seen as a result of release of endogenous pyrogens like IL-1 and IL-8. Reactive lymphadenopathies
may also be seen.