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*'''Immune-mediated disease''' including [[Immune Mediated Haemolytic Anaemia]] and [[Neonatal Isoerythrolysis]].
 
*'''Immune-mediated disease''' including [[Immune Mediated Haemolytic Anaemia]] and [[Neonatal Isoerythrolysis]].
 
*'''Infectious agents''' including ''[[Babesia|Babesia spp.]]'' in dogs and cattle, ''[[Feline Infectious Anaemia|Mycoplasma haemofelis]]'' in cats, ''[[Leptospira|Leptospira spp.]]'' in various species and ''[[Clostridium haemolyticum]]'' causing redwater fever in cattle.
 
*'''Infectious agents''' including ''[[Babesia|Babesia spp.]]'' in dogs and cattle, ''[[Feline Infectious Anaemia|Mycoplasma haemofelis]]'' in cats, ''[[Leptospira|Leptospira spp.]]'' in various species and ''[[Clostridium haemolyticum]]'' causing redwater fever in cattle.
*'''Haemotrophic mycoplasmas.''' (Haemoplasmas) are small bacteria that attach to the external erythrocyte membrane. There are multiple species which vary in pathogenicity. In the cat Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’ and ‘Candidatus Mycoplasma turicensis’ are seen most frequently; a further species, ‘Candidatus Mycoplasma haematoparvum-like’ has been reported in the literature. Mycoplasma haemofelis is the most pathogenic, producing anaemia and clinical signs of disease. ‘Candidatus Mycoplasma haemominutum’ and ‘Candidatus Mycoplasma turicensis’ may cause some changes in red cell parameters but anaemia is only seen in cats with concurrent disease (Retroviral infection), immunocompromised cats or those receiving corticosteroid therapy. In dogs Mycoplasma haemocanis and ‘Candidatus Mycoplasma haematoparvum’ have been identified and may cause haemolytic anaemia in splenectomised or immunocompromised dogs. The method of choice for diagnosis is PCR using appropriate controls on EDTA blood samples. Previously diagnosis was by examination of air-dried blood smears (not EDTA smears) to search for the organisms. Even in the acute phase, parasitaemia is not always present so it may be necessary to take blood and make smears on 5-7 consecutive days. The organisms are very small and must be distinguished from stain precipitate in Romanowsky stained smears, Howell- Jolly bodies and background debris. They may be seen as very small organisms on the periphery of the erythrocyte or form chains and rings. May-Grunwald or acridine orange stains may increasethe sensitivity of blood film examination. References: [[/en.wikivet.net/NationWide Laboratories|NationWide Laboratories]]
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*'''Haemotrophic mycoplasmas.''' (Haemoplasmas) are small bacteria that attach to the external erythrocyte membrane. There are multiple species which vary in pathogenicity. In the cat Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’ and ‘Candidatus Mycoplasma turicensis’ are seen most frequently; a further species, ‘Candidatus Mycoplasma haematoparvum-like’ has been reported in the literature. Mycoplasma haemofelis is the most pathogenic, producing anaemia and clinical signs of disease. ‘Candidatus Mycoplasma haemominutum’ and ‘Candidatus Mycoplasma turicensis’ may cause some changes in red cell parameters but anaemia is only seen in cats with concurrent disease (Retroviral infection), immunocompromised cats or those receiving corticosteroid therapy. In dogs Mycoplasma haemocanis and ‘Candidatus Mycoplasma haematoparvum’ have been identified and may cause haemolytic anaemia in splenectomised or immunocompromised dogs. The method of choice for diagnosis is PCR using appropriate controls on EDTA blood samples. Previously diagnosis was by examination of air-dried blood smears (not EDTA smears) to search for the organisms. Even in the acute phase, parasitaemia is not always present so it may be necessary to take blood and make smears on 5-7 consecutive days. The organisms are very small and must be distinguished from stain precipitate in Romanowsky stained smears, Howell- Jolly bodies and background debris. They may be seen as very small organisms on the periphery of the erythrocyte or form chains and rings. May-Grunwald or acridine orange stains may increasethe sensitivity of blood film examination. References: [[NationWide Laboratories]]
 
*'''Inherited defects of red blood cells enzymes''' including pyruvate kinase (which is occur most commonly in West Highland white terriers) and phosphofructokinase (PFK).  
 
*'''Inherited defects of red blood cells enzymes''' including pyruvate kinase (which is occur most commonly in West Highland white terriers) and phosphofructokinase (PFK).  
 
*'''Pyruvate Kinase deficiency.''' This is an autosomal recessive genetic disease in dogs causing severe persistant extravascular haemolysis. There is usually moderate to severe anaemia (PCV18-25%) with marked reticulocytosis, possibly due to rapid RBC turnover and splenomegaly. PK-deficient RBCs have a shortened life span with inefficient energy production. Affected dogs are young and usually die by the age of 3 years with, in many cases, myelofibrosis and osteosclerosis. PK deficiency is transmitted as an autosomal recessive trait in many breeds of dogs with the highest prevalence in Basenji’s and Beagle’s. PK deficiency has been reported in the DSH, Abyssinian and Somali breeds of cat. References: [[NationWide Laboratories]]
 
*'''Pyruvate Kinase deficiency.''' This is an autosomal recessive genetic disease in dogs causing severe persistant extravascular haemolysis. There is usually moderate to severe anaemia (PCV18-25%) with marked reticulocytosis, possibly due to rapid RBC turnover and splenomegaly. PK-deficient RBCs have a shortened life span with inefficient energy production. Affected dogs are young and usually die by the age of 3 years with, in many cases, myelofibrosis and osteosclerosis. PK deficiency is transmitted as an autosomal recessive trait in many breeds of dogs with the highest prevalence in Basenji’s and Beagle’s. PK deficiency has been reported in the DSH, Abyssinian and Somali breeds of cat. References: [[NationWide Laboratories]]
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*'''Hypophosphataemia''' which occurs in post-parturient cattle (causing post-parturient haemoglobinuria), with refeeding syndrome and when animals with [[Diabetes Mellitus|diabetes mellitus]] are stabilised with insulin.
 
*'''Hypophosphataemia''' which occurs in post-parturient cattle (causing post-parturient haemoglobinuria), with refeeding syndrome and when animals with [[Diabetes Mellitus|diabetes mellitus]] are stabilised with insulin.
 
*Exposure to '''toxins''' including rape and kale (which contain SMCO radicals) in cattle, onions and garlic in dogs and paracetamol in cats.
 
*Exposure to '''toxins''' including rape and kale (which contain SMCO radicals) in cattle, onions and garlic in dogs and paracetamol in cats.
*'''Microangiopathic anaemia''' which occurs when red blood cells are forced through small meshworks of fibrin as with [[Haemangiosarcoma|haemangiosarcomas]], [[Disseminated Intravascular Coagulation|disseminated intravascular coagulation]] (DIC) or bacterial endocarditis.This is usually a mild, often subclinical anaemia unless there is concurrent haemorrhage from, for example, a tumour. RBCs are damaged as they pass through abnormal vessels or regions of turbulent blood flow, giving rise to schistocytes. These fragmented red cells are phagocytosed by the mononuclear phagocytic system, causing anaemia. Numerous schistocytes in a smear are always significant. References: [[/en.wikivet.net/NationWide Laboratories|NationWide Laboratories]]  
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*'''Microangiopathic anaemia''' which occurs when red blood cells are forced through small meshworks of fibrin as with [[Haemangiosarcoma|haemangiosarcomas]], [[Disseminated Intravascular Coagulation|disseminated intravascular coagulation]] (DIC) or bacterial endocarditis.This is usually a mild, often subclinical anaemia unless there is concurrent haemorrhage from, for example, a tumour. RBCs are damaged as they pass through abnormal vessels or regions of turbulent blood flow, giving rise to schistocytes. These fragmented red cells are phagocytosed by the mononuclear phagocytic system, causing anaemia. Numerous schistocytes in a smear are always significant. References: [[NationWide Laboratories]]
 
Haemolysis usually results in a more strongly regenerative response than haemorrhage and can be differentiated by plasma protein concentrations; these will fall with haemorrhage, but not with haemolysis.
 
Haemolysis usually results in a more strongly regenerative response than haemorrhage and can be differentiated by plasma protein concentrations; these will fall with haemorrhage, but not with haemolysis.
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The failure to regenerate indicates that there is a failure to produce red blood cells in the bone marrow.  Erythrocytes are produced from stem cells in the bone marrow and they then undergo sequential stages of maturation before and after they are released into the circulation.   
 
The failure to regenerate indicates that there is a failure to produce red blood cells in the bone marrow.  Erythrocytes are produced from stem cells in the bone marrow and they then undergo sequential stages of maturation before and after they are released into the circulation.   
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===Failure of the bone marrow stem cells to produce erythroid cells===
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An inadequate degree of reticulocytosis is the essential diagnostic feature. Some reticulocytes may be present but fewer than required for a given degree of anaemia, after sufficient time has elapsed for an erythroid response to have developed. These anaemias are mainly normochromic normocytic. References: [[/en.wikivet.net/NationWide Laboratories|NationWide Laboratories]] 
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=== Primary Anaemia: Failure of the bone marrow stem cells to produce erythroid cells ===
 
This occurs in the following conditions:
 
This occurs in the following conditions:
*'''[[Immune Mediated Haemolytic Anaemia|Pure red cell aplasia]]'''
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*Aplastic anaemia
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'''Bone marrow diseases'''. A method for bone marrow aspiration can be found in the cytology section. Where bone marrow hypoplasia is suspected a core biopsy in formalin should also be taken.
*Bone marrow suppression
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*Myelophthisis
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'''Bicytopaenia or pancytopaenia.''' Reflects poor marrow production of two or three cell lines. This suggests marrow disease. Because of the long life span of RBCs, anaemia is usually detected later than neutropaenia and thrombocytopaenia.
*Myelodysplasia
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'''Aplastic pancytopaenia and myelofibrosis.''' These conditions require bone marrow histopathology to confirm the diagnosis. A core biopsy is essential to differentiate between a poor bone marrow aspirate sample and poor cellularity. In aplastic anaemia the haematopoietic bone marrow is replaced by fat, in myelofibrosis by fibrous tissue. Causes include drug toxicity, viruses and immune-mediated processes. Pure red cell aplasia causes severe nonregenerative anaemia with in the marrow, normal myeloid and megakaryocytic cells but no erythroid precursors. It is thought to be immune-mediated and may respond to steroid therapy.
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'''Dyserythropoiesis.''' There are a variety of causes including B12 or folate deficiency, iron deficiency, drug toxicities. These are nonregenerative anaemias with normal to increased erythroid precursor cells in the bone marrow. There are blast cells, binucleate RBC precursors, macrocytes megaloblasts and asynchronous maturation of the cytoplasm and nucleus.
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'''Proliferative disorders.''' Can also cause nonregenerative anaemia as neoplastic cells over-run the bone marrow (myelophthisic disease).
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'''[[Immune Mediated Haemolytic Anaemia|Pure red cell aplasia]]'''
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Myelophthisis
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Myelodysplasia
    
===Failure of erythrocyte maturation===
 
===Failure of erythrocyte maturation===

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