Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Cocker Spaniel

Cocker Spaniel (English & American)

Primary Immune-Mediated Haemolytic Anaemia

Related terms: autoimmune haemolytic anaemia, immune-mediated haemolytic anaemia, idiopathic immune-mediated haemolytic anaemia

Outline: Cocker spaniels are predisposed to immune-mediated haemolytic anaemia but the genetic basis of the disease is unknown. For some reason, antibodies are produced that attack the red blood cells causing anaemia that can be severe and fatal. It causes malaise, pain and distress that can last for weeks or month. Breeding dogs from lineages with little or no history of the disease is likely to reduce its prevalence.


Summary of Information

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1. Brief description

In animals affected with haemolytic anaemia the life span of their red blood cells (RBCs) is reduced: they are broken down more rapidly than the bone marrow can make replacements so that the number of red blood cells circulating drops below normal and this leads to disease. Haemolytic anaemia can be caused by a variety of factors including toxins, infections and congenital and metabolic causes, but the most common form– primary immune-mediated haemolytic anaemia (IMHA) - is due to a malfunction of the immune system (Mackin 2002, Miller 2009).

The reason why the immune system starts to attack the red blood cells is unknown. It occurs most commonly in middle age dogs and is more likely to occur in females than males (Mackin 2002, Weinkle et al 2005, Miller 2009).

In IMHA, the body develops antibodies against some of the proteins that make up the surface of red blood cells (Barkerm et al 1991). Antibodies are specialised proteins produced by the immune system that target and identify specific disease-causing organisms or foreign material, marking them for destruction by other parts of the immune system. Normally, antibodies are developed only against foreign molecules or organisms such as toxins, parasites or bacteria. In IMHA the immune system malfunctions, with otherwise normal red blood cells being marked for destruction. 

The haemolytic anaemia that results from this destruction of the red blood cells has serious effects in most affected dogs and may cause death of many, despite treatment. The effects include: damage to organs from lack of oxygen, widespread damage to tissue structure and function due to toxins associated with poor liver function, and abnormalities of blood clotting leading to blockage of blood vessels.

2. Intensity of welfare impact    

Dogs with IMHA feel ill because of the effects of the disease. They may suffer pain because of disruption to blood flow and oxygen supply that results from the anaemia and the development of blood clots. Respiration may be compromised causing further distress. Treatment may also have adverse welfare effects associated with the hospitalization of the affected animal, procedures such as blood transfusions and from the administration and side effects of drugs. Drug treatments for IMHA inlcude the ami nistration of high-doses of corticosteroids and chemotherapeutic drugs that frequently, as side-effects, cause gastrointestinal damage or bone marrow suppression (Miller 2009, Ramsey 2011).

Surgery to remove the spleen is sometimes recommended. This is a major procedure with a risk of death and has other repercussions for the welfare of the animal, associated with their hospitalization and pain from the procedure.

3. Duration of welfare impact

IMHA causes significant welfare problems lasting from days to weeks during the time when treatment is being attempted. Around 40-60% of dogs die from the disease in this time, either directly from the disease or due to euthanasia if treatment is ineffective or unavailable (Weinkle et al 2005, Reimer et al 1999, Stokol et al 2000, Mackin 2002, Miller 2009). Some dogs respond to treatment and recover but a significant proportion of these are at risk of further episodes of haemolysis and some die during these subsequent episodes. Long-term use of drugs may cause long-term welfare problems (Miller 2009, Ramsey 2011).

4. Number of animals affected

Cocker spaniels are known to be predisposed to this condition but we are unaware of any data on the proportion of that are affected (Feldman 1996, Reimer et al 1999, Burgess et al 2002, Carr et al 2002, Mackin 2002, Miller et al 2004, Weinkle et al 2005, Miller 2009).

5. Diagnosis

Anaemia is diagnosed by examination of blood samples and the finding of a reduced red cell concentration. Evaluation of routine blood tests may indicate that the cause is due to haemolysis (ie that the anaemia is due to increased rate of loss of red cells) rather than bleeding or a decreased rate of red blood cell production. Establishing the cause of the haemolysis depends largely on ruling out other possible causes. There is no definitive test for primary IMHA (Mackin 2002, Miller 2009).

6. Genetics

Cocker spaniels are known to be predisposed to this condition but we are unaware of any data on the proportion that are affected (Feldman 1996, Reimer et al 1999, Burgess et al 2002, Carr et al 2002, Mackin 2002, Miller et al 2004, Weinkle et al 2005, Miller 2009).

7. How do you know if an animal is a carrier or likely to become affected?

It is not possible to predict which dogs may develop the disease or pass it on to their offspring: no test is available. Those with affected close relatives (parents, siblings, grandparents and the siblings of parents and grandparents) may be more likely to develop or carry the disease than those from lineages in which the disease has not been detected or has been rare.

8. Methods and prospects for elimination of the problem

As far as we are aware, there are currently no organised schemes aimed at reducing the prevalence of IMHA in cocker spaniels. Whilst the genes involved have not been determined, breeding selectively from cocker spaniels whose lineages have a history of no, or low, incidence of the disease is likely to be effective in reducing the number of affected dogs (Indrebo 2006, Bell 2010).


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1. Clinical and pathological effects

Red blood cells transport oxygen around the body. They are produced in the bone marrow and then enter the blood stream where they circulate around the body and function for about three months. At the end of their life span, they are removed from circulation and broken down in the liver and spleen.

In haemolytic anaemia, the length of time that red blood cells spend circulating around the body before being broken down is reduced and, if their rate of loss exceeds the rate at which they are produced, the concentration of red cells in the blood drops leading to disease. Haemolytic anaemia can be caused by various factors including toxins, infections (especially infections of the RBCs themselves), and congenital and metabolic causes. The most common cause in cocker spaniels, however, is primary immune-mediated haemolytic anaemia IMHA (Mackin 2002, Miller 2009).

In IMHA, antibodies are formed against some of the proteins that make up the surface of red blood cells (Barkerm et al 1991). Antibodies are specialised proteins produced by the immune system that target and identify specific disease-causing organisms or foreign material, marking them for destruction by other parts of the immune system. Normally, antibodies are developed only against foreign molecules or organisms such as toxins, parasites or bacteria. However, in animals with IMHA the immune system malfunctions, and otherwise normal red blood cells are marked for destruction. Antibodies that attack the animal's own tissues and molecules are termed autoantibodies and the diseases they cause are described as autoimmune diseases. In IMHA autoantibodies coat the surface of the red blood cells and one of the two further pathological processes outlined below occurs (Mackin 2002, Miller 2009).

1. There may be extravascular haemolysis, in which the red cells are removed from circulation and broken down by the spleen and liver.

2. Or there may be intravascular haemolysis, in which the red blood cells are coated with so many antibodies and other factors produced by the immune system that they break down whilst still circulating in blood vessels. This leads to a more severe form of the disease.

The reason why the immune system starts to attack the RBCs is unknown. It occurs most commonly in middle-aged dogs and is more likely to occur in females than in males (Mackin 2002, Miller et al 2004, Weinkle et al 2005, Miller 2009).

There are a number of possible consequences of this haemolytic process, as outlined below.

1. The anaemia may be severe enough to result in oxygen transport and supply to the tissues to be inadequate for their needs. This causes lethargy and malaise, and reduced activity and appetite are common. Heart rate may be elevated to compensate, to some extent, for the poor oxygen-carrying capacity of the blood. As the anaemia becomes worse, organ damage occurs, which may be very severe, due to insufficient oxygen supply.

2. There may be an inflammatory reaction associated with the haemolysis of the red blood cells and there may be a fever.

3. Jaundice, a yellow colouration of the body often visible in the mouth and eyes but also on the skin and with the production of darker urine, may occur if the liver cannot process the breakdown products of the red blood cells as quickly as they are produced. When intravascular haemolysis has occurred the urine may be a red colour. Jaundice reflects a build up of toxic products in the blood and contributes to a feeling of illness. It can also lead to kidney failure.

4. Dogs with IMHA are prone to develop thromboembolisms – blood clots that form within the circulatory system causing blockage of vessels. These can occur anywhere and result in damage to any tissues or organs whose blood supply they disrupt. The most common sites for thromboembolisms are the lungs, where their occurrence leads to breathing distress (Scott-Moncrieff et al 2001, Carr et al 2002).

5. Around 10% of dogs with IMHA also have an autoimmune disease directed against platelets (thrombocytes), which are other components of blood vital for clotting. In these cases, there may be a failure of clotting such that affected dogs may develop haemmorhages despite little or no trauma and pin-point haemorrhages may be visible in unpigmented tissues e.g. in the mouth. The condition when both IMT and IMHA are present has been termed Evan’s syndrome (Wilkins et al 1973, Williams & Maggio-Price 1984, Jackson & Kruth 1985).

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2. Intensity of welfare impact

Dogs with IMHA feel ill because of the effects of the disease and a high proportion of dogs die (Miller 2009). Disease in breeds prone to develop the problem may be more likely to be severe than in the average dog (Feldman 1996). They may suffer pain because of disruption to blood flow and oxygen supply that results from the anaemia and the development of blood clots. Respiration may be compromised causing further distress. Treatment may also have adverse welfare effects associated with the hospitalization of the affected animal, procedures such as blood transfusions and from the administration and side effects of drugs. Dru treatments for IMHA include the administration of high-doses of corticosteroids and chemotherapeutic drugs that frequently, as side-effects, cause gastrointestinal damage or bone marrow suppression (Miller 2009, Ramsey 2011).

Surgery to remove the spleen is sometimes recommended. This is a major procedure with a risk of death and has other repercussions for the welfare of the animal, associated with their hospitalization and pain from the procedure.

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3. Duration of welfare impact

IMHA causes significant welfare problems lasting from days to weeks during the time when treatment is being attempted. Around 40-60% of dogs die from the disease in this time either directly from the disease or due to euthanasia if treatment is ineffective or unavailable (Weinkle et al 2005, Reimer et al 1999, Stokol et al 2000, Mackin 2002, Miller 2009). Some dogs respond to treatment and recover but a significant proportion of these are at risk of further episodes of haemolysis and some die during these subsequent episodes. Long-term use of drugs may cause long-term welfare problems (Miller 2009, Ramsey 2011).

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4. Number of animals affected

Cocker spaniels are known to be predisposed to this condition but we are unaware of any data on the proportion that are affected (Feldman 1996, Reimer et al 1999, Burgess et al 2002, Carr et al 2002, Mackin 2002, Miller et al 2004, Weinkle et al 2005 Miller 2009). 

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5. Diagnosis

The diagnosis of anaemia is made by detection of an abnormally low concentration of red blood cells during the laboratory examination of a blood sample. It is usually possible to establish that the cause is due to haemolysis from evaluation of routine blood tests, although sometimes this requires further tests, for example to check for abnormal red blood cells (spherocytes), or for agglutination (clumping) of the blood when it is mixed with saline on a glass slide. Agglutination should not normally occur and, if it does, is an indication that the red cells are coated with autoantibodies. A specific test, the Coomb’s test, can be used to detect the presence of these antibodies. Establishing the cause of the haemolysis depends largely on ruling out other possible causes.  There is no definitive test for primary IMHA (Mackin 2002, Miller 2009).

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6. Genetics

Cocker spaniels are known to have a breed predisposition for IMHA but the genetic basis of this is unknown (Feldman 1996, Reimer et al 1999, Burgess et al 2002, Carr et al 2002, Mackin 2002, Miller et al 2004, Weinkle et al 2005 Miller 2009).

Miller et al (2004) and Kennedy et al (2006) studied the effect of tissue type (which is a genetically controlled characteristic – for example blood group) on how likely a dog was to suffer from immune mediated haemolytic anaemia and found that there were differences. This gives further evidence of a genetic component for the disease.

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7. How do you know if an animal is a carrier or likely to become affected?

It is not possible to predict which dogs may develop the disease or pass it on to their offspring: no test is available. Those with affected close relatives (parents, siblings, grandparents and the siblings of parents and grandparents) may be more likely to develop or carry the disease than those from lineages in which the disease has not been detected or has been rare.

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8. Methods and prospects for elimination of the problem

As far as we are aware, there are currently no organised schemes aimed at reducing the prevalence of IMHA in cocker spaniels. Whilst the genes involved have not been determined, breeding selectively from cocker spaniels whose lineages have a history of no, or low, incidence of the disease is likely to be effective in reducing the number of affected dogs (Indrebo 2006, Bell 2010).

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

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10. References

Barkerm RN, Gruffydd-Jones TJ, Stokes CR and Elson CJ (1991) Identification of autoantigens in canine autoimmune haemolytic anaemia. Clinical & Experimental Immunology 85: 33–40

Bell JS (2010) Genetic Testing and Genetic Counseling in Pet and Breeding Dogs. 35th World Small Animal Veterinary Association World Congress Proceedings. 2-5th June 2010, Geneva, Switzerland. http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2010&PID=pr56159&O=VIN accessed 21.7.2011

Burgess K, Moore A, Rand W and Cotter SM (2000) Treatment of Immune-Mediated Hemolytic Anemia in Dogs with Cyclophosphamide. Journal of Veterinary Internal Medicine 14: 456–462

Carr AP, Panciera DL and Kidd L (2002) Prognostic Factors for Mortality and Thromboembolism in Canine Immune-Mediated Hemolytic Anemia: A Retrospective Study of 72 Dogs. Journal of Veterinary Internal Medicine 16: 504–509

Feldman BF (1996) Demographics of canine immune-mediated haemolytic anaemia in the Southeastern United States Comparative Haematology International 6: 42-45

Indrebo A (2006) Healthy Dog Breeding -The Value of Breeding Programmes. World Small Animal Veterinary Association Proceedings http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2006&PID=pr15830&O=VIN accessed 21.7.2011

Jackson ML and Kruth SA (1985) Immune-mediate haemolytic anaemia and thrombocytopenia in the dog: a retrospective study of 55 cases diagnosed from 1969 through 1983 at the Western College of Veterinary Medicine. Canadian Veterinary Journal 26: 245-250

Kennedy LJ, Barnes A, Ollier WER and Day MJ (2006) Association of a common dog leucocyte antigen class II haplotype with canine primary immune-mediated haemolytic anaemia. Tissue Antigens 68: 502–508.

Mackin A (2002) Immune-Mediated Hemolytic Anemia: Pathophysiology and Diagnosis Proceedings of the American College of Veterinary Internal Medicine 2002 http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=acvim2002&PID=pr01915&O=VIN  accessed 15.11.2011

Miller SA, Hohenhaus AE and Hale AS (2004) Case-control study of blood type, breed, sex, and bacteremia in dogs with immune-mediated hemolytic anemia. Journal of the American Veterinary Medical Association 224: 232-235

Miller E (2009) Immune-mediated haemolytic anemia. In: Kirk’s Current Veterinary Therapy XIV editors JD Bonagura & DC Twedt, Saunders Elsevier, St Louis pp 266

Ramsey I (2011) Prednisolone. In: BSAVA Small Animal Formulary 7th edition, British Small Animal Veterinary Association, Cheltenham UK pp 33

Reimer ME, Troy GC and Warnick LD (1999) Immune-mediated hemolytic anemia: 70 cases (1988-1996). Journal of the American Animal Hospital Association 35: 384-91

Scott-Moncrieff JC, Treadwell NG, McCullough SM and Brooks MB (2001) Hemostatic abnormalities in dogs with primary immune-mediated hemolytic anemia. Journal of the American Animal Hospital Association 37: 220-7

Stokol T, Blue JT and French TW (2000) Idiopathic pure red cell aplasia and nonregenerative immune-mediated anemia in dogs: 43 cases (1988-1999). Journal of the American Veterinary Medical Association 216: 1429-36

Weinkle TK, Center SA, Randolph JF Warnr KL, Barr SC and Erb HN (2005) Evaluation of Prognostic Factors, Survival Rates, and Treatment Protocols for Immune-Mediated Hemolytic Anemia in Dogs: 151 Cases (1993-2002). Journal of the American Veterinary Medical Association 226: 1869-1880

Wilkins RJ, Hurvitz AL and Dodds WJ (1973) Immunologically mediated thrombocytopenia in the dog. Journal of the American Veterinary Medical Association 163: 277-82

Williams DA and Maggio-Price (1984) Canine idiopathic thrombocytopenia: clinical observations and long-term follow-up in 54 cases. Journal of the Veterinary Medical Association 185: 660

© UFAW 2012


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