Tracee - I am so so sorry to read this. Understandably you must be devastated - its a tremendous shock to lose them so young, and so suddenly. Auto immune diseases can be very unforgiving and sadly if the vet isn't fully aware of the symptoms then results can be tragic. I wish I had joined a few days ago, I'm so sorry.
Here is one of the articles Jo has written - I hope its not too long to post here - and I hope it explains things to you all - feel free to ask any questions whatsoever, Jo and I spend a lot of time trying to help people with their poorly pets with AI diseases.
AUTOIMMUNE HAEMOLYTIC ANAEMIA (AIHA)
IMMUNE MEDIATED HAEMOLYTIC ANAEMIA (IMHA)
There can be several reasons why a dog may become anaemic (having a depleted number of red blood cells within the circulation of the blood) i.e. autoimmune disease (or immune mediated disease), tick borne diseases such as ehrlichia, Babesia and Lyme disease, cancers, parasites, poisoning (zinc, onions etc), a reaction to drug administration, hyperthermia, systemic disease. However, primary autoimmune haemolytic anaemia (AIHA) is the most common, non traumatic cause of anaemia in the dog, and its incidence is increasing.
This article attempts to outline certain important aspects of the disease so that clinical signs may be recognised by the owner of an anaemic dog and aid an early diagnosis and correct treatment of this very serious condition.
GENETIC PREDISPOSITION
Statistics show that AIHA is more common in dogs of young to middle age, but breeds that are known to be genetically predisposed have, by definition, an increased susceptibility. Dogs have been known to have AHIA as young as 3 months, ranging to 12 years of age and over.
TRIGGER FACTOR
AIHA may be triggered by an infection, vaccination, stress, drugs, chemicals, hormones etc and reports show a higher incidence of AIHA in females, particularly following a season or whelping. Unfortunately, the owner maybe unaware of the disease having been triggered until clinical signs appear which, depending on whether the anaemia
is acute or chronic, may range from only a couple of days, to a few weeks, or even longer after the ‘trigger’ event.
DISEASE PROCESS
Trigger factors, most of which are unknown, cause the body’s immune system to react to antigens - proteins that form part of the membrane of the red blood cell - as if they were foreign invaders.
The immune system is designed to bind antibodies to foreign antigens and remove them safely from the body. When AIHA occurs, the antigens attach to the dog’s red blood cells, so when the antigens are destroyed and removed from the body, so too are healthy red blood cells. Thus resulting in autoimmune haemolytic anaemia. The body’s immune defence system turns on itself and the destruction may not stop until all the red cell-bound antigens are removed from the body.
In some cases the autoantibody is directed against the immature red blood cells in the bone marrow. This is a severe non-regenerative form of anaemia. If the correct treatment for AIHA is not given, the dog will become progressively more anaemic, ultimately it will die.
AIHA can occur in conjunction with other autoimmune diseases such as Systemic Lupus Erythematosus (SLE), a multi-systemic autoimmune disease, and Immune Mediated Thrombocytopenia (IMTP) an immune destruction of the blood platelets (Evan’s Syndrome).
CLINICAL SIGNS - the dog may show some signs of the following:
Weakness
Pale mucous membranes (gums, eyes, genital organs)
Lethargy
Exercise intolerance
Increased breathing rate
Increased pulse rate
Anorexia/weight loss (loss of appetite)
Depression
Bright orange coloured urine
Bright orange coloured faeces
Jaundice (yellow discoloration of mucous membranes)
Fever - low grade
Vomiting
Collapse
Diarrhoea
Craving to eat soil
Occasionally increased drinking and urination
Enlarged spleen, liver, lymph nodes
Skin lesions, including sloughing of skin on the ear tips
Heart murmurs and gallop and other abnormal rhythms
If IMTP is also present - blood blisters on mucous membranes, bruising and black, tarry stools.
If SLE is also present - joint pain and/or kidney glomerulonephritis
CLASSIFICATION AND DIAGNOSIS
Immune Mediated Haemolytic Anaemia (IMHA) can be either regenerative or non-regenerative as determined by laboratory examination of a blood sample and/or bone marrow biopsy.
Regenerative anaemia is characterised by the presence of increased numbers of large immature red blood cells (reticulocytes) in the circulation.
Non-regenerative anaemia is an anaemia lasting longer that 5 days, with an appropriately low reticulocyte count in the circulation.
Clinical presentation of AIHA may be acute, subacute or chronic. Dogs with acute or subacute intravascular haemolytic anaemia (within the circulation) have a rapid onset of the disease and have little time to adapt to the depletion of red cells, therefore signs of extreme weakness, collapse, vomiting, raised temperature and jaundice are often present. A Coomb’s blood test is performed to check for antiglobulins.
In chronic AHIA it may take weeks or months for clinical signs to show. This form of AIHA, initially, is very well tolerated and shows minimal, clinical signs, and the dog can adjust to the slow onset of the disease.
Dogs with chronic AIHA may have episodes of jaundice, collapse, and show clinical signs that ‘wax and wane’. Eventually, because this form of AIHA is non-regenerative, (the immature red cells are being made but are destroyed in the bone marrow by the dog’s own immune system) the dog will become progressively, more severely anaemic.
Without a bone marrow biopsy it is impossible to distinguish between non-regenerative AIHA and cancer, or other causes of non-regenerative haemolytic anaemia. Even in regenerative anaemias, a positive Coomb’s test doesn’t necessarily prove AIHA or a negative result rule it out.
It appears that some vets’ are not aware that an immune mediated destruction of the immature red cells can occur in the bone marrow and have wrongly assumed that cancer of the bone marrow is the cause of the dog’s non-regenerative anaemia. Usually the prognosis given by the vet is grave, and very little or no treatment is offered. Surprisingly, very few owners are offered a bone marrow biopsy for their dog, which could confirm a diagnosis of cancer or an immune mediated disease.
‘Canine Medicine & Therapeutics’ by Neil Gorman lists six possible diseases, in the blood analysis section for differential diagnoses for leukaemia. Five are cancers and the other one is “immune mediated disease”.
In fact, four out of five categories in the diagnosis of leukaemia, lists among the differential diagnoses “immune mediated disease”. Despite this, some vets do not even consider that non-regenerative anaemia COULD be an immune mediated disease.
In some cases of chronic anaemia, when the dog has become very anaemic (red cell blood count nearing 12%) the vet has treated the dog speculatively for AIHA (e.g. based on clinical signs, without a definitive diagnosis). The alternative to this is that the dog will get weaker and weaker, as it becomes progressively more anaemic, and eventually has to be put to sleep to avoid further suffering.
Treating clinical signs without a diagnosis, is not the ideal situation, but vets do it every day. There are very few conditions that vets can categorically diagnose on the spot without test results - and yet it is common practice to give antibiotics or anti-inflammatory drugs, steroids etc., on the assumption that the dog will improve if treated.
If the prognosis of clinical signs is very poor, but there may be a chance of survival if the dog is treated appropriately for AIHA, then treatment should be offered. What is there to lose? Many dogs have been treated in this way and have responded well, and have survived. If the dog’s red blood cell count is 12% or less (normal PCV range: 35-55% - in puppies and certain breeds of dog, this may vary) then a blood transfusion may be necessary to ‘buy time’ for the drugs to take effect. Early treatment improves the prognosis of AIHA.
Immunosuppressive drugs are used to treat leukaemia as well as AIHA, IMTP and SLE, and there is no reason not to treat any dog suspected of having any of these diseases with high doses of prednisolone, provided a bacterial, viral or fungal cause of the signs has been ruled out.
RANGE OF TREATMENT FOR AIHA
“In most cases the primary treatment involves immunosuppressive doses of oral corticosteroid (e.g. Prednisone or prednisolone 2 - 4mg/kg q24hr divided into twice daily dosing, starting at 2mg/kg and only increase dosage if response is poor. This should be given for at least 2-4 weeks, and then if the PCV - Packed Cell Volume
(% of red blood cells within the blood) is stable, decrease to 1mg/kg/24 hours for 2-4 weeks, then 1mg/kg/48hours for another 2-4 weeks, then gradually taper off. If at anytime the PCV falls, the veterinary surgeon should return to the previous dose that was working.
A gastroprotectant such as sucralfate (0.5-1g twice a day) should be given whilst the dog is on high doses of steroids.
In patients with refractory or severe anaemia, cytotoxic/immunosuppresive drugs such as azathioprine (50mg/Mªq 24h (2mg/kg p/o q24h), for 1-2 weeks, then every other day, or cyclophosphamide (50mg/Mªp/o q24h (2mg/kg q 24h) for the first four days of each week for 6-8 weeks, then reassess) should be included in the regime and will eventually enable a reduced dose of glucocorticoid to be used. Since time is of the essence, it is advisable to commence these as soon as possible in those patients with severe disease.
Danazol (synthetic androgen; 5mg/kg p/o q12h). Although Danazol is usually well tolerated, the drug is expensive and is usually reserved for patients that are either refractory to a combination of prednisolone and azathioprine or cyclophosphamide, or intolerant of drug side-effects. It appears to act synergistically with corticosteroids for the treatment of AIHA and IMTP, however it is contraindicated in patients who also have heart, liver or kidney problems.
Cyclosporin (15mg/kg p/o q24h) has been used to treat refractory AIHA.
Supportive therapy (fluids or blood transfusion) may be required in life-threatening anaemias. A transfusion may ‘buy time’ until therapy becomes effective (typically 3-7 days). However, the process which destroyed the dog’s own red cells will rapidly destroy the transfused ones also, if treatment is delayed. Usually, cross-matched packed red cells only, are preferred where available. The average circulating life-span of a red blood cell is approximately 110-120 days.
A splenectomy (removal of the spleen) is usually a last resort in patients with life- threatening refractory anaemia and should be considered if medical management is not controlling the disease after 4-6 weeks of therapy.
I hope that the above information will not apply to any of your dogs, now or in the future. It is only submitted in the knowledge that “awareness can save lives”.
If you require any further information please contact:
CIMDA (Canine Immune Mediated Disease Awareness) jo@cimda.fsnet.co.uk
Jo Tucker
References:
Linda Aronson DVM, MA
Clinical Immunology of the Cat & Dog - by Michael J Day
Canine Medicine & Therapeutics - by Neil Gorman
Special thanks to Dr. Linda Aronson, for her support and assistance in the composition of this article.
