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==Signalment==
 
==Signalment==
Primary IMHA occurs with greater frequency in Cocker spaniels<ref>Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN. '''Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).''' ''J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80.''</ref>, Old English sheepdogs and standard Poodles but any breed of dog may be affected.  Middle-aged, entire female animals have been shown to be at increased risk of developing the disease in some studies.
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Primary IMHA occurs with greater frequency in Cocker spaniels<ref>Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN. '''Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).''' ''J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80.''</ref><ref>McAlees TJ. '''Immune-mediated haemolytic anaemia in 110 dogs in Victoria, Australia.''' ''Aust Vet J. 2010 Jan;88(1-2):25-8.''</ref>, Old English sheepdogs and standard Poodles but any breed of dog may be affected.  Middle-aged, entire female animals have been shown to be at increased risk of developing the disease in some studies.
    
==Diagnosis==
 
==Diagnosis==
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===Stabilisation===
 
===Stabilisation===
In animals that have lost a large percentage of their [[Packed Cell Volume|PCV]] acutely, it is likely that a [[Blood Transfusion|blood transfusion]] will be required.  Since animals with IMHA are not usually hypovolaemic, packed red blood cells are often transfused to replace erythrocytes without significantly expanding the plasma volume.  In emergency situations, whole blood or synthetic haemoglobin molcules (such as Oxyglobin [tm]) may be used to support the oxygen carrying capacity of the patient.  Oxygen may be provided to tachypnoeic and dyspnoeic patients by facemask, nasal catheter or flow-by.  
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In animals that have lost a large percentage of their [[Packed Cell Volume|PCV]] acutely, it is likely that a [[Blood Products|blood transfusion]] will be required.  Since animals with IMHA are not usually hypovolaemic, packed red blood cells are often transfused to replace erythrocytes without significantly expanding the plasma volume.  In emergency situations, whole blood or synthetic haemoglobin molcules (such as Oxyglobin [tm]) may be used to support the oxygen carrying capacity of the patient.  Oxygen may be provided to tachypnoeic and dyspnoeic patients by facemask, nasal catheter or flow-by.  
    
===Immunosuppressive Therapy===
 
===Immunosuppressive Therapy===
 
Whatever supportive measures are taken, the autoimmune response must be controlled to prevent the continuing lysis of red blood cells.  The following types of drug are typically used to achieve this goal:
 
Whatever supportive measures are taken, the autoimmune response must be controlled to prevent the continuing lysis of red blood cells.  The following types of drug are typically used to achieve this goal:
*'''Corticosteroids''' such as prednisolone and dexamethasone are used universally as a first-line treatment for IMHA as they are frequently effective, act rapidly and are available in a variety of preparations.  Traditionally, very high doses of corticosteroids have been used to try to control the autoimmune response but dose rates beyond 2-3 mg/kg may be associated with significant adverse effects.  More recently, there has been a move to add further immunosuppressive agents (see below) in a polypharmaceutical approach which allows the clinician to keep the corticosteroid dose rate at a reasonable level.  Corticosteroids act to control both the cell- and antibody-mediated immune responses.
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*'''Corticosteroids''' such as prednisolone and dexamethasone are used universally as a first-line treatment for IMHA as they are frequently effective, act rapidly and are available in a variety of preparations.  Traditionally, very high doses of corticosteroids have been used to try to control the autoimmune response but dose rates beyond 2-3 mg/kg/day may be associated with significant adverse effects.  More recently, there has been a move to add further immunosuppressive agents (see below) in a polypharmaceutical approach which allows the clinician to keep the corticosteroid dose rate at a reasonable level.  Corticosteroids act to control both the cell- and antibody-mediated immune responses.
 
*'''Azathioprine''' is frequently used in the management of IMHA and it has effects on both cell- and antibody-mediated immune responses.  It may take 3-4 weeks of treatment before the patient experiences the maximal effects of the drug.  Azathioprine is a cytotoxic drug and gloves should be worn to administer tablets.  Owners or keepers should be made aware that the active drug or its metabolites may be present in the saliva and other secretions of animals receiving the drug.
 
*'''Azathioprine''' is frequently used in the management of IMHA and it has effects on both cell- and antibody-mediated immune responses.  It may take 3-4 weeks of treatment before the patient experiences the maximal effects of the drug.  Azathioprine is a cytotoxic drug and gloves should be worn to administer tablets.  Owners or keepers should be made aware that the active drug or its metabolites may be present in the saliva and other secretions of animals receiving the drug.
 
*'''Ciclosporin A''' is a fungal metabolite that inhibits a signaling molecule (ciclophilin) involved in T cell activation.  Since B cells require T cell help to become activated, differentiate into plasma cells and produce antibodies, there is a rationale for the use of ciclosporin in cases of IMHA but there are currently no reports of its relative efficacy compared to the other immunosuppressive drugs.   
 
*'''Ciclosporin A''' is a fungal metabolite that inhibits a signaling molecule (ciclophilin) involved in T cell activation.  Since B cells require T cell help to become activated, differentiate into plasma cells and produce antibodies, there is a rationale for the use of ciclosporin in cases of IMHA but there are currently no reports of its relative efficacy compared to the other immunosuppressive drugs.   
*Other less commonly-used drugs include danazol (a steroid related to testosterone), mycophenolate mofetil and cyclophosphamide.  Cyclophosphamide was used widely in the management of IMHA but two separate studies have shown that its use is associated with higher rates of mortality.
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*Other less commonly-used drugs include danazol (a steroid related to testosterone), mycophenolate mofetil and cyclophosphamide.  Cyclophosphamide was used widely in the management of IMHA but two separate studies have shown that its use is associated with higher rates of mortality<ref>Grundy SA, Barton C. '''Influence of drug treatment on survival of dogs with immune-mediated hemolytic anemia: 88 cases (1989-1999).''' ''J Am Vet Med Assoc. 2001 Feb 15;218(4):543-6.''</ref><ref>Burgess K, Moore A, Rand W, Cotter SM. '''Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.''' ''J Vet Intern Med. 2000 Jul-Aug;14(4):456-62.''</ref><ref>Mason N, Duval D, Shofer FS, Giger U. '''Cyclophosphamide exerts no beneficial effect over prednisone alone in the initial treatment of acute immune-mediated hemolytic anemia in dogs: a randomized controlled clinical trial.''' ''J Vet Intern Med. 2003 Mar-Apr;17(2):206-12.''</ref>.
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*'''Human gamma globulin''' is a variably popular product that is thought to act by occupying Fc receptors on cells of the MPS and therefore preventing phagocytosis of opsonised red blood cells.  Studies investigating the effects of this drug have produced variable results, with some showing that it makes little difference to outcome<ref>Whelan MF, O'Toole TE, Chan DL, Rozanski EA, DeLaforcade AM, Crawford SL, Cotter SM. '''Use of human immunoglobulin in addition to glucocorticoids for the initial treatment of dogs with immune-mediated hemolytic anemia.''' ''J Vet Emerg Crit Care (San Antonio). 2009 Apr;19(2):158-64.''</ref> and others suggesting that it may be useful in the short-term control of cases that are refractory to other immunosuppressive regimes<ref>Kellerman DL, Bruyette DS. '''Intravenous human immunoglobulin for the treatment of immune-mediated hemolytic anemia in 13 dogs.''' ''J Vet Intern Med. 1997 Nov-Dec;11(6):327-32.''</ref>.  Human gamma globulin is not widely available in veterinary practices and it is very expensive.
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*Due to the risk of thrombo-embolism caused by the release of endogenous procoagulant molecules, low doses of '''heparin''' or '''aspirin''' are often administered to dogs with IMHA to try to prevent the formation of thrombi in the lungs, liver or spleen.  There is some evidence to suggest that, if a dose of heparin is used which is individualised for a particular patient, there may be beneficial effects on survival<ref>Helmond SE, Polzin DJ, Armstrong PJ, Finke M, Smith SA. '''Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs.''' ''J Vet Intern Med. 2010 May-Jun;24(3):597-605. Epub 2010 Apr 6.''</ref>.  This effect is not observed if a constant dose of heparin is used for all patients<ref>Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN. '''Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).''' ''J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80.''</ref>.
    
===Adjunctive Therapy===
 
===Adjunctive Therapy===
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==Prognosis==
 
==Prognosis==
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Most mortality occurs in the first two weeks after presentation and, overall, 30-50% of animals would be expected to survive for at least one year after initial treatment for IMHA<ref>'''Idiopathic immune-mediated hemolytic anemia: treatment outcome and prognostic factors in 149 dogs.''' ''Piek CJ, Junius G, Dekker A, Schrauwen E, Slappendel RJ, Teske E.'' J Vet Intern Med. 2008 Mar-Apr;22(2):366-73. Epub 2008 Mar 10.</ref>.
 
==References==
 
==References==
 
<references/>
 
<references/>
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[[Category:To Do - James]]
 
[[Category:To Do - James]]
 
[[Category:Dog]][[Category:Cat]]
 
[[Category:Dog]][[Category:Cat]]
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[[Category:To Do - Review]]
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