Primary and secondary IMHA
Table 2: Selected Causes of Canine and Feline IMHA
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IMHA has been described in people, dogs, cats, and a wide range of other species.2 In dogs, it is estimated that 60% to 75% of cases are considered primary (idiopathic), meaning that no underlying cause
can be found.3 It is thought that as more intense clinical investigations are conducted in these patients, underlying diseases and triggers
will be discovered.3 Any breed can be affected with primary IMHA, but certain breeds—such as cocker spaniels, poodles, Irish setters, and Old
English sheepdogs—seem to be overrepresented (Table 2).1 In both people and dogs, there appears to be a linkage between specific human leukocyte antigen (HLA) and dog leukocyte
antigen (DLA) haplotypes and autoimmune disease, although the genes involved may differ for each disease. A recent study in
dogs investigated whether a genetic mutation in the DLA of certain breeds predisposes them to IMHA. The results suggest that
more than one gene may be involved in these susceptible breeds.4
In secondary IMHA, RBC destruction occurs as a consequence of the immune system reacting to some condition or being activated
by an agent. The end result is that the RBCs are destroyed as innocent bystanders. The process is probably the result of several
factors, including an animal's susceptibility to disease and its propensity to form an autoimmune response. Usually, the process
results from a combination of environmental factors and a genetic predisposition. The cellular mechanisms by which an agent
can cause autoimmunity can include infection of immune cells, activation of lymphocytes from exposure to cytokines, cross-reactivity
between microorganisms and host tissues, and the production of drug-specific antibodies with the formation of immune complexes.2 The loss of self-tolerance, resulting in autoimmunity, is also a mechanism by which hemolytic anemia can occur.
A recent report linked the class III antiarrhythmic agent amiodarone with a positive Coombs test result in two dogs. One of
these patients developed hemolytic anemia, the other developed thrombocytopenia.5 Another report discussed intravascular hemolysis associated with a patent ductus arteriosus coil embolization in a dog.6 Examples of possible underlying conditions causing secondary IMHA are listed in Table 2 and include infections, drugs, and neoplasia, as well as other immune-related disorders. Secondary IMHA is the common type
of immune-mediated hemolysis in cats.1
In certain infectious diseases, such as mycoplasmosis and babesiosis, hemolysis caused by the organism is exacerbated by the
body's own immune response. If you suspect an infectious disease, administer antibiotics pending the results of antibody titers
or polymerase chain reaction (PCR) testing. Additionally, to reduce the body's response to the infectious agent, immunosuppressive
medications often need to be administered. Once an underlying infectious agent is identified, the immunosuppressive medications
can be used at lower doses and for an abridged treatment course.
PATHOPHYSIOLOGY
IMHA is a type II hypersensitivity reaction in which RBCs are destroyed by the body's own immune system. The process typically
involves a breakdown of immune self-tolerance and the production of anti-erythrocyte antibodies, IgG, or IgM. These antibodies
are often recognizing and reacting to RBC membrane glycoproteins.7 Erythrocyte destruction is initiated when the surface becomes coated with complement and either IgM or IgG.8
The most common form of IMHA is IgG-mediated. The IgG-coated RBCs are destroyed by macrophages located in the liver or spleen
(extravascular). Macrophages either consume the entire erythrocyte or remove a portion of the membrane, leaving smaller RBCs
with no central pallor (spherocytes). These rigid spherocytes are then trapped in the spleen and destroyed. IgM-coated RBCs
will also activate complement more efficiently than IgG, with destruction generally occurring within vessels (intravascular).1
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