Immune-Mediated Hemolytic Anemia
Etiology and pathophysiology:
The cause of IMHA has been discussed at length. Genetics are involved as there are breed predispositions such as the Cocker
Spaniel. In addition gender may also play a role. The reason why a predisposition exists are to date unclear, though they
may have something to do with red blood cell antigens or the way the immune system works. Various triggers are also thought
to play a role. Vaccination has also been incriminated. In one paper 25% of dogs had been vaccinated within the last month
before presentation. In several other papers an association has not been seen. Certainly in my research such a link could
not be made. Drug administration and infections may also play a role. The majority of cases are idiopathic.
Once the process has been initiated, red cells are tagged for destruction by the binding of immunoglobulins or complement.
Depending upon how tagged, the RBCs will be destroyed either intravascularly or extravascularly. The sites of red cell removal
include liver, spleen and bone marrow. The autoantibodies can be directed at very early RBCs such as reticulocytes causing
an anemia that appears non-regenerative as the precursors are removed first.
Diagnosis with IMHA can proceed along the name of the disease. All components of the name, that is "immune-mediated" "hemolytic"
and "anemia" need to be satisfied for a definitive diagnosis. Anemia is usually the easiest part to determine. At times one
or the other areas will be present without being able to satisfy the others. This is the case when a positive Coombs test
is present in an animal without anemia. This does not diagnose IMHA, in fact it may be a marker for neoplasia.
There are a variety of ways to determine that an anemia is immune-mediated. One way is a positive Coombs test, unfortunately
both false positive and false negative results occur. The Coombs test identifies bound immunoglobulins or complement on the
RBCs. Some types of antibodies will be picked up better than others and at times processing of the RBCs wash the antibodies
off. Overall it still is a very good test. The presence of autoagglutination is definitive for IMHA. It must be differentiated
from Rouleaux formation by diluting 1 drop of blood with several drops of saline. If gross agglutination is not seen, look
at the slide under a microscope for aggregates of clumped RBCs. The presence of a large number of spherocytes is also a strong
indicator of IMHA (pieces of the RBC membrane have been removed, leaving more hemoglobin behind in a smaller RBC).
Hemolysis must also be present to confirm IMHA. Spherocytes are a sign of both immune-mediated destruction as well as hemolysis.
Icterus is if present can indicate hemolysis, though the degree of jaundice will depend upon the rapidity of hemolysis as
well as possible damage to the liver (hypoxia through anemia, thrombi). Hemoglobinuria is also a strong indicator of hemolysis
if urinary tract disease has been ruled out. Hemolysis determined on a blood draw is however very easy to induce, even in
normal animals so it has be interpreted carefully.
It is important to remember that all the various areas must be present to have a definitive diagnosis of IMHA. Hemolysis can
occur through mechanisms that are not immune mediated. Anemia can be caused by many problems. Unfortunately in some cases
all the pieces of the puzzle will not fit together and the diagnosis will merely be presumptive. A definitive diagnosis does
allow a very aggressive treatment approach. If not definitive, frequent reassessment is indicated to make sure another disease
process has not been overlooked.