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secondary in nature. Removal of the triggering agent or treatment of the underlying condition can bring the IMHA rapidly under control.
Fluids, Blood Transfusions, Oxygen and Oxyglobin in IMHA
Restoration and maintenance of tissue perfusion with crystalloid fluids is important, even when it results in further lowering of the hematocrit. When severe anemia and a dropping hematocrit lead to signs of tissue hypoxia, packed red blood cell transfusions appear beneficial. The increased oxygen-carrying capacity provided by the transfused red blood cells may be sufficient to maintain the animal’s hematocrit for a few days, while other treatment modalities have time to become effective. The notion that transfusions pose
an increased hazard to animals with IMHA has been overemphasized and is not supported by retrospective clinical studies. Fresher blood products are possibly an advantage. However, the common occurrence
of autoagglutination may make blood typing and crossmatching of the patient impossible. In these cases DEA 1- blood should be transfused. Additional blood types are being recognized which may be also important.
If compatible blood is not available, the bovine hemoglobin solution Oxyglobin, a highly purified
bovine hemoglobin solution, if available, may be administered and provides increased oxygen-carrying capacity and plasma expansion. The original FDA study documented the beneficial effects of Oxyglobin in dogs, whereas recent retrospective studies do not allow
any conclusions. In contrast to blood and Oxyglobin, oxygen inhalation therapy is of little benefit, unless the animal with IMHA is suffering form pulmonary disease such as pulmonary thromboembolism. Thanks to adequate transfusion support, animals with IMHA rarely die because of anemia, but because of secondary complications such as thromboemboli and infections.
Immunosuppressive Therapy for IMHA
The insufficient understanding of the pathogenesis, the generally guarded prognosis, the lack of good therapeutic trials, the serious drug side effects, and the high costs of intensive care greatly hamper the successful management of dogs with IMHA. The main goal of immunosuppressive therapy is to reduce (1) phagocytosis, (2) complement activation, and (3) anti- erythrocytic antibody production. Glucocorticoids are the initial treatment of choice for canine, feline and human IMHA. They interfere with both the expression and function of macrophage Fc receptors and thereby immediately impair the clearance of antibody-coated erythrocytes by the macrophage system. In addition, glucocorticoids reduce the degree of antibody binding and complement activation on erythrocytes, and only after weeks, diminish the production of autoantibodies.
Thus, oral prednisolone at a dose of 1-2 mg/kg twice daily is the mainstay treatment. Alternatively, oral or parenteral dexamethasone at an equipotent dose of 0.6 mg/kg daily can be used, but is likely not more beneficial.
There is no evidence that other immunosuppressive agents are effective. They should not be used initially as they are associated with severe side effects. Additional immunosuppressive therapy is warranted when prednisone fails, only controls the disease at persistently high doses, or when it causes unacceptable side effects. They are generally used together with prednisolone,
but may eventually be used independently. Historically, cytotoxic drugs such as cyclophosphamide were
added, however a small randomized study and several retrospective surveys failed to show any beneficial effects, but may be associated with greater morbidity and mortality in the acute management of IMHA. Retrospective studies and anecdotal reports with azathioprine, cyclosporine, danazol, mycophenylate,
and human intravenous immunoglobulin suggest
some efficacy, but controlled prospective clinical trials that document their efficacy are lacking. For instance, there is no evidence that azathioprine is effective and from a mechanistic view point it only inhibits antibody production and as it is an antimetabolite, it is only effective after a few weeks. Furthermore, the side effects of acute pancreatitis and agranulocytosis to aplasia makes this in most cases unsuitable. Cyclosporine
at 5-10 mg/kg is likely the best and safest second
agent but blood drug levels have to be determined
in order to avoid toxicity and underdosing. Highly immunosuppressive agents from transplantation medicine such as mycophenylate and leflunamide are other agents which have been tried but no definitive beneficial effects have been reported. Finally, human intravenous immunoglobulin at 2 x 1 g/kg may rescue a non-responding IMHA patient but relapses are common.
One other agent is melatonin which has been added
as immunotherapy which is begin but it is unclear if
this has any beneficial effects. Splenectomy may be considered particularly in refractory cases with large spleen, but even a normal spleen may excessively clear antibody-coated red blood cells. Furthermore, splenic histopathology, toxicology and infectious disease screens may offer a diagnosis of an underlying disease. Finally, because of the apparently severe agglutination and the inflammatory and necrotic process, plasma exchange therapy has been used in a few cases and appeared to be helpful in expediting response and avoiding serious complications.
It should be noted that an apparent therapeutic response to immunosuppressive therapy is insufficient evidence for the diagnosis of IMHA. Response to therapy may
be indicated by a hematocrit that rises or stabilizes, an appropriate reticulocytosis, diminished autoagglutination,
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