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Mycophenolate mofetil treatment of immune-mediated hemolytic anemia
PAG E 4
A D VA N C E S
MYCOPHENOLATE MOFETIL TREATMENT OF IMMUNEMEDIATED HEMOLYTIC ANEMIA Background Primary immune-mediated hemolytic anemia (IMHA) occurs less frequently in cats than in dogs. In cats, hemolytic anemia is more often caused by infectious diseases, exposure to chemicals or toxins, severe hypophosphatemia, drug reaction, neoplasia, or immune reactions against transfused red blood cells (RBC). A diagnosis of primary/idiopathic IMHA is made when the inciting cause for antibody formation cannot be identified. Secondary IMHA in cats is often triggered by infectious diseases (Mycoplasma spp.), feline leukemia virus, feline immunodeficiency virus, and feline infectious peritonitis. Supportive care for feline primary IMHA is generally similar to treatments used in dogs. Glucocorticoids are the recommended initial immunosuppressive agent. Initial prednisolone doses of 2 to 4 mg/kg are suggested. Other drugs, such as cyclosporine, cyclophosphamide, and chlorambucil have been administered along with glucocorticoids in nonresponsive or poorly responsive cases. Mycophenolate mofetil (MMF) is the prodrug form of mycophenolic acid. MMF is most commonly used to prevent organ rejection in human transplant patients. Recently, there has been increased interest in using MMF in dogs with autoimmune disorders.
A D VA N C E S
Objectives To describe the use of oral MMF as an adjunctive therapy in 2 cats with primary IMHA.
Case Reports Case 1: A 2-year-old, spayed female domestic short-hair cat weighing 4.2 kg was presented for evaluation of acute onset lethargy and anorexia. MMF (10 mg/kg, by mouth, every 12 hours) treatment was initiated due to a lack of response to immunosuppressive steroid therapy. Previously administered doxycycline and prednisolone were continued. Remission gradually occurred. Prednisolone was continuing to be slowly tapered and the MMF was discontinued after 2 months of therapy. The cat has been clinically normal at home and is currently on prednisolone (0.5 mg/kg, by mouth, every 12 hours). Case 2: A 10-year-old, spayed female Himalayan cat weighing 3.4 kg was presented for further evaluation of anemia. The cat was retrovirus (FeLV and FIV) negative and lived indoors only. She had been diagnosed previously with asthma and was maintained on once-daily montelukast (2 mg, by mouth). She was current on vaccinations. Other treatments with doxycycline, famotidine, and dexamethasone were continued. MMF (10 mg/kg, by mouth, every 12 hours) was initiated, because the packed cell volume was not maintaining post-transfusion. The cat improved and was discharged on prednisolone, famotidine, doxycycline, and MMF.
Author Conclusion This is the first reported use of oral MMF as adjunctive treatment for cats with IMHA. Outcome was favorable in both cats and no adverse effects were noted from the MMF.
Inclusions Twenty two references.
Editor Annotation IMHA continues to be one of the most frustrating diseases to treat in small animal medicine. The fact that there are so many manuscripts addressing the disease and its treatment is a testament in itself that there is no easy answer to treatment. This is the first manuscript describing the use of MMF to treat IMHA in cats. It
is a case series of only 2 cats, yet information obtained from the manuscript is potentially important and helpful. There are few minor pitfalls of the manuscript. The cases are referred to as primary IMHA. However, work-up to completely rule out secondary causes was not complete (e.g., no bone marrow analysis and only 2-view thoracic radiographs in both cases, no abdominal ultrasound in the first case, and one case was already receiving a medication the time of diagnosis). In both cases, the authors state or imply that MMF was added as a treatment, because the IMHA was refractory to treatment with prednisolone alone. However, MMF was used on day 2 in one case and day 3 in the second case, which most would argue is a premature judgment that the disease was refractory to prednisolone therapy. Prednisone is not expected by most clinicians to work that quickly. The rise in hematocrit after institution of MMF is not complete evidence that the MMF worked, as the prednisolone and/or doxycycline used and continued in both cases may have taken that long to become effective. Potentially helpful information from this manuscript includes: • No appreciable adverse effects in the cases, although data is again limited to only 2 cases
• Encouraging preliminary data about MMF for the use of IMHA in cats
• Justification for future prospective studies In the editor’s experience, the incidence of feline IMHA is rare compared that in the dog, but it is becoming apparently more common. Potential reasons for the apparent increased incidence in cats includes there may be new infectious diseases about which we are not aware and thus cannot test for, genetics, or improved recognition of IMHA in cats. IMHA is a complicated disease for numerous reasons, including different causes, and every animal and disease responds somewhat differently to medications. The fact that there are so many manuscripts and drugs out there further exemplifies there is not one great treatment. It is important to know the treatment options, as well as to have some idea about what to expect when using a drug for the purpose of treating feline IMHA. (LDM) Bacek LM, Macintire DK. Treatment of primary
PAG E 5
immune-mediated hemolytic anemia with mycophenolate mofetil in two cats. J Vet Emerg Crit Care 2011;21:45-49.
A D VA N C E S
MYCOPHENOLATE MOFETIL TREATMENT OF IMMUNEMEDIATED HEMOLYTIC ANEMIA Background Primary immune-mediated hemolytic anemia (IMHA) occurs less frequently in cats than in dogs. In cats, hemolytic anemia is more often caused by infectious diseases, exposure to chemicals or toxins, severe hypophosphatemia, drug reaction, neoplasia, or immune reactions against transfused red blood cells (RBC). A diagnosis of primary/idiopathic IMHA is made when the inciting cause for antibody formation cannot be identified. Secondary IMHA in cats is often triggered by infectious diseases (Mycoplasma spp.), feline leukemia virus, feline immunodeficiency virus, and feline infectious peritonitis. Supportive care for feline primary IMHA is generally similar to treatments used in dogs. Glucocorticoids are the recommended initial immunosuppressive agent. Initial prednisolone doses of 2 to 4 mg/kg are suggested. Other drugs, such as cyclosporine, cyclophosphamide, and chlorambucil have been administered along with glucocorticoids in nonresponsive or poorly responsive cases. Mycophenolate mofetil (MMF) is the prodrug form of mycophenolic acid. MMF is most commonly used to prevent organ rejection in human transplant patients. Recently, there has been increased interest in using MMF in dogs with autoimmune disorders.
A D VA N C E S
Objectives To describe the use of oral MMF as an adjunctive therapy in 2 cats with primary IMHA.
Case Reports Case 1: A 2-year-old, spayed female domestic short-hair cat weighing 4.2 kg was presented for evaluation of acute onset lethargy and anorexia. MMF (10 mg/kg, by mouth, every 12 hours) treatment was initiated due to a lack of response to immunosuppressive steroid therapy. Previously administered doxycycline and prednisolone were continued. Remission gradually occurred. Prednisolone was continuing to be slowly tapered and the MMF was discontinued after 2 months of therapy. The cat has been clinically normal at home and is currently on prednisolone (0.5 mg/kg, by mouth, every 12 hours). Case 2: A 10-year-old, spayed female Himalayan cat weighing 3.4 kg was presented for further evaluation of anemia. The cat was retrovirus (FeLV and FIV) negative and lived indoors only. She had been diagnosed previously with asthma and was maintained on once-daily montelukast (2 mg, by mouth). She was current on vaccinations. Other treatments with doxycycline, famotidine, and dexamethasone were continued. MMF (10 mg/kg, by mouth, every 12 hours) was initiated, because the packed cell volume was not maintaining post-transfusion. The cat improved and was discharged on prednisolone, famotidine, doxycycline, and MMF.
Author Conclusion This is the first reported use of oral MMF as adjunctive treatment for cats with IMHA. Outcome was favorable in both cats and no adverse effects were noted from the MMF.
Inclusions Twenty two references.
Editor Annotation IMHA continues to be one of the most frustrating diseases to treat in small animal medicine. The fact that there are so many manuscripts addressing the disease and its treatment is a testament in itself that there is no easy answer to treatment. This is the first manuscript describing the use of MMF to treat IMHA in cats. It
is a case series of only 2 cats, yet information obtained from the manuscript is potentially important and helpful. There are few minor pitfalls of the manuscript. The cases are referred to as primary IMHA. However, work-up to completely rule out secondary causes was not complete (e.g., no bone marrow analysis and only 2-view thoracic radiographs in both cases, no abdominal ultrasound in the first case, and one case was already receiving a medication the time of diagnosis). In both cases, the authors state or imply that MMF was added as a treatment, because the IMHA was refractory to treatment with prednisolone alone. However, MMF was used on day 2 in one case and day 3 in the second case, which most would argue is a premature judgment that the disease was refractory to prednisolone therapy. Prednisone is not expected by most clinicians to work that quickly. The rise in hematocrit after institution of MMF is not complete evidence that the MMF worked, as the prednisolone and/or doxycycline used and continued in both cases may have taken that long to become effective. Potentially helpful information from this manuscript includes: • No appreciable adverse effects in the cases, although data is again limited to only 2 cases
• Encouraging preliminary data about MMF for the use of IMHA in cats
• Justification for future prospective studies In the editor’s experience, the incidence of feline IMHA is rare compared that in the dog, but it is becoming apparently more common. Potential reasons for the apparent increased incidence in cats includes there may be new infectious diseases about which we are not aware and thus cannot test for, genetics, or improved recognition of IMHA in cats. IMHA is a complicated disease for numerous reasons, including different causes, and every animal and disease responds somewhat differently to medications. The fact that there are so many manuscripts and drugs out there further exemplifies there is not one great treatment. It is important to know the treatment options, as well as to have some idea about what to expect when using a drug for the purpose of treating feline IMHA. (LDM) Bacek LM, Macintire DK. Treatment of primary
PAG E 5
immune-mediated hemolytic anemia with mycophenolate mofetil in two cats. J Vet Emerg Crit Care 2011;21:45-49.