Veterinary Medicine - December 2008 - (Page 667)

intravascular hemolysis, or thrombocytopenia), when glucocorticoids do not adequately control the hemolysis, or when the side effects of glucocorticoids become unacceptable. The use of multiple cytotoxic drugs in combination requires careful monitoring, however, as there is a risk of severe immunosuppression and danger of infection.27 Corticosteroids. Dexamethasone (0.1 to 0.3 mg/kg intravenously once or twice daily) can be given initially if oral medications cannot be tolerated. Prednisone or prednisolone (2 mg/kg orally once or twice daily) is the oral drug of choice. Glucocorticoids are thought to prevent hemolysis by decreasing the clearance of antibody-coated RBCs by macrophages, reducing the amount of antibody binding and complement activation on RBCs, and, in the long-term, minimizing autoantibody production.1 Side effects include polyuria, polydipsia, polyphagia, increased panting, gastrointestinal ulceration, and increased susceptibility to infection. Azathioprine. In cases of severe IMHA (low RBC counts, autoagglutination, or intravascular hemolysis), the second drug usually added in dogs is azathioprine (2 mg/kg orally once daily or every other day). Studies have shown increased survival times in dogs treated with glucocorticoids and azathioprine.13,28 Drawbacks to this medication are that it is only available in oral form and it can take weeks to take effect. Azathioprine is a purine analogue antimetabolite that disrupts DNA and RNA synthesis and is effective in limiting cell-mediated immunity (T-lymphocyte function).24 Side effects can include gastrointestinal upset, bone marrow suppression, pancreatitis, and hepatotoxicity. Regular physical examinations and complete blood counts and serum chemistry pro les (weekly at rst, then monthly) will help to monitor for the more serious complications of this medication. Azathioprine can cause severe bone marrow and hepatic toxicosis in cats and is not recommended.24 Cyclosporine. A third drug gaining acceptance in treating IMHA is cyclosporine (2.5 to 5 mg/kg orally twice daily). An intravenous form is available, but no clinical trials with this form have been published in the veterinary literature. The one retrospective study that investigated cyclosporine (which was given at a slightly higher than recommended dosage) showed no bene t compared with other drug protocols.29 Cyclosporine is a potent T-cell suppressor that blocks production of immune activating factors in both T-helper cells and T-cytotoxic cells, as well as blocks the expression of IL-2 and gamma-interferon. The outcome is a reduction of cell-mediated immunity and antibody production. Side effects include gastrointestinal upset, gingival hyperplasia (can regress with dose tapering), increased susceptibility to infection, and lethargy. Although it is recommended that cyclosporine concentrations are measured every two to four weeks (maintaining trough concentrations, depending on the method used, between 100 and 300 ng/ml), it is now questionable whether blood concentrations of this drug need to be measured if clinical disease is well-controlled.17 Cyclophosphamide. In addition to the above therapeutic options, a handful of other medications have been used with varying degrees of success. Cyclophosphamide, an alkylating agent that suppresses the immune system, can be given as a single intravenous or oral dose initially in the course of treatment (200 mg/m2) or as a four days on/three days off (50 mg/m2/day) protocol. Cyclophosphamide harms B and T cells by cross-linking DNA, inhibiting humoral and cell-mediated immunity, and suppressing neutrophil and macrophage function. Side effects include gastrointestinal upset, myelosuppression, and hemorrhagic cystitis. Because of the severity of some of these signs, cyclophosphamide is not widely used in the long-term treatment of IMHA. Instead, it is commonly used in early treatment of severe refractory IMHA. Cyclophosphamide has fallen out of favor since a randomized, controlled, prospective clinical trial published in 2003 showed no improved recovery or survival times in patients treated with cyclophosphamide and prednisone vs. prednisone alone.30 Many other studies have also documented decreased survival in patients treated with cyclophosphamide.13,29,30 Mycophenolate mofetil. Mycophenolate mofetil (10 to 20 mg/kg orally or intravenously twice daily), similar to azathioprine, targets B and T lymphocytes by inhibiting an enzyme necessary for de novo purine biosynthesis.15 This drug was developed to help prevent allograft rejection in people and has been used in dogs to treat myasthenia gravis and glomerulonephritis. At therapeutic doses, mycophenolate is minimally myelosuppressive, but gastrointestinal side effects can be substantial in dogs (gastrointestinal hemorrhage, anorexia, and diarrhea). To minimize these side effects, the dose can be lowered to well-tolerated levels when used in conjunction with other myelosuppressive drugs.31 Few reports have been published on the use of this drug for IMHA.32 Danazol. Danazol (5 mg/kg orally two to three times daily), a synthetic androgen, has been used to treat immune-mediated disease in people and is sometimes recommended in addition to standard therapies to treat IMHA in dogs. Danazol likely exerts its immunomodulatory effects by decreasing the production of IgG and cytokines, inhibiting complement activation, and reducing the binding of antibody and complement to erythrocytes.24 Danazol is not widely used for three main reasons: it is expensive, it can take weeks to observe a clinical response, and it is potentially hepatotoxic.1 While one study did not show improved outcome with this drug, the small number of reports in the veterinary literature makes the use of this drug dif cult to assess.33 VETERINARY MEDICINE December 2008 667

Table of Contents Feed for the Digital Edition of Veterinary Medicine - December 2008

Veterinary Medicine - December 2008 Contents Letters Thanking Our Valued Reviewers Practical Matters Idea Exchange Why Do Dogs and Cats Eat Grass? Managing Atypical and Critical Cases of Primary Hypoadrenocorticism in Dogs Behaviors Suggestive of Postoperative Pain in Cats What to Consider When Considering Digital Radiography Avoid Common Bandaging Mistakes in Dogs and Cats IMHA: Diagnosing and Treating a Complex Disease CE Form/Advertiser Index Marketplace/Classifieds Mind Over Miller

Veterinary Medicine - December 2008

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