IMHA: Diagnosing and treating a complex disease - Veterinary Medicine
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IMHA: Diagnosing and treating a complex disease
Differentiating IMHA from other causes of hemolytic anemia is challenging, but a careful diagnostic process will help you determine whether your veterinary patients will require long-term immunosuppressive therapy.


Primary and secondary IMHA

Table 2: Selected Causes of Canine and Feline IMHA
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.


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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