IMHA (immune-mediated haemolytic anaemia) is a condition where the body's immune system attacks its own red cells. This can lead to life-threatening anaemia and a host of other serious complications.

Think of red cells like little trucks. They pick up loads of oxygen at the lung depot and then driving around the body (via blood vessels) delivering the oxygen to the cells, where they also collect waste carbon dioxide and take it back to the lungs. Without enough trucks (anaemia), the rest of the body's cells are starved of oxygen – they become weak and may even die.

IMHA is like a corrupt police force taking over and pulling the trucks off the road for no good reason. Let's look at how the immune system gets corrupted and what we can do about it.

 
Maltese.jpg

Normal red cell life cycle

Red cells are made from stem cells in the bone marrow. They go through a few 'maturation stages' in the bone marrow and then get released into the bloodstream where they do they oxygen-carrying job for around 120 days. As they age, they become less flexible until they are too stiff to fit through the smallest blood vessels in the body (the capillaries).

Old red cells are removed from the circulation by the spleen, liver and bone marrow (mainly the spleen) in a process called extravascular haemolysis. The red cells are broken down by immune cells called macrophages in these organs. Some red cell components (eg iron and amino acids) are recycled and some are discarded (eg bilirubin, which is the pigment of bile, faeces and urine). If you're really interested, watch the YouTube video below.

It's not just old cells that are destroyed. Damaged red blood cells are also p[ucked from the circulation. There are several ways that red cells can become damaged. Drugs and toxins can do it, as can passing through abnormal blood vessels (such as in tumours). They can also become infected. The spleen can pick which ones need removing because the immune system has tagged them – it's stuck antibodies to the surface of the red cells.

Sometimes the red cells are destroyed within the circulation. This is called intravascular haemolysis.

 

What happens in IMHA?

In IMHA there is an abnormal (short) red cell life cycle.

The clue is in the name:

  • immune-mediated – means the disease is due the body's own immune system (instead of leaving the red cells alone to do their job, the immune system recognises them as foreign invaders and attacks them)
  • haemolytic – means red cell destruction ('haem' refers to haemoglobin contained in red cells and 'lytic' refers to disintegration)
  • anaemia – means a lack of red blood cells

So if you develop IMHA, your immune system starts wiping out your red cells at a faster rate than usual. When too many red cells are removed from the circulation for normal processes to cope, we can see some serious problems:

  • weakness and lethargy (due to lack of oxygen and build up of waste)
  • the liver can't process all of the bilirubin and it ends up in the bloodstream and tissues (causing the appearance of jaundice)
  • the bilirubin in the blood can damage the kidneys
  • the red cells covered in antibodies become sticky and can clump together forming clots – these can lodge in small blood vessels blocking supply to organs (especially the lungs where they cause pulmonary thromboembolism)

Pretty quickly we have a life-threatening crisis. IMHA has a 20–80% mortality rate (depending on the study). Of the animals that die from IMHA, about 80% show evidence of thromboembolism on autopsy.

 
OESD.png

Who gets IMHA?

Both dogs and cats can suffer from IMHA.

Cocker Spaniels have a genetic predisposition to developing IMHA. Other commonly affected breeds include Mini Poodles, Irish Setters, English Springer Spaniels, Old English Sheepdogs, Dobermanns, Collies, Bichon Frises, Mini Pins and Finnish Spitz.

Female dogs might have a higher risk than males. It's also more common in middle age.

(When it comes to cats, the good old Domestic Short Hair is most commonly affected, and males are more at risk than females.)

 

What causes IMHA?

In the majority of cases, we can't find a cause for IMHA – the body just appears to suddenly start attacking itself. 

Sometimes there is an underlying cause. Examples include: infection, cancer, some medications/drugs, lupus, incompatibility between a mother's and baby's blood type, and blood transfusion reactions.

IMHA can occur together with other immune-mediated disorders. One reasonably common scenario is IMHA with immune-mediated thrombocytopaenia (IMT or IMTP), which describes destruction of platelets. This is called Evan's syndrome.

 
aussie.jpg

What are the signs of IMHA?

The signs you might see at home include:

  • lethargy and weakness (with possible collapse)
  • exercise intolerance
  • loss of appetite
  • increased rate and effort of breathing (as the body tries to get more oxygen in)
  • vomiting and diarrhoea (stools may be dark and tarry)
  • dark coloured urine
  • pale gums (gums get the pinkness from red cells) or possible yellow tinged
  • rapid heart rate (as the body tries harder to pump oxygen around the body)

On physical examination, we may also pick up:

  • an enlarged spleen and/or liver
  • fever
  • enlarged lymph nodes
  • a heart murmur (called a haemic murmur that occurs due to 'thin' blood)
  • signs of a clotting disorder
  • necrosis of peripheral tissues (feet and ears)
 

How is IMHA diagnosed?

Whenever we see an animal with anaemia, we have to work out which of three processes are going on:

  • are the red cells being lost through bleeding (haemorrhage)?
  • is the bone marrow not making new red cells?
  • are the red cells being destroyed (haemolysed)?

The easiest one to diagnose is haemorrhage, although most of the time there is no visible bleeding. When you lose red cells through bleeding, you also lose other things in blood such as protein. So a low protein level is a clue to haemorrhage. One of the most useful diagnostic tools we use here is ultrasound. This can easily pick up fluid (blood) accumulation in body cavities and can also pick up underlying causes such as splenic and liver tumours.

If the bone marrow is not making new red cells, we see what's called a non-regenerative anaemia. In this case, there are no immature red cells in the circulation. It takes around 3–4 days after the loss of red cells for the bone marrow to respond, so early on it can be difficult to diagnose this one. Getting to the bottom of this type of anaemia may require a bone marrow biopsy.

Clues we look for when investigating IMHA include:

  • the presence of damaged red cells called spherocytes – these have passed through the spleen and instead of being completely removed, a 'bite' has been taken out of them, then they've escaped back into the circulation (spherocytes are found in 94% of cases)
  • clumping together of red cells called autoagglutination (found in 42% of cases)
  • signs that the bone marrow is working really hard and not just making new red cells but white cells too (this is called a leukaemoid reaction)

If we have these three things, we can pretty confident in diagnosing IMHA. There are times when the clues are missing or less clear and we need further testing, such as a Coomb's test.

 
ChineseCrested.png

How is IMHA treated?

Transfusions

Patients with IMHA are often critically ill on presentation. Their red cell count might be so low as to place them at imminent risk of dying. Before we can treat the disease, we have to stabilise the patient with one or more blood transfusions. Transfusions don't treat the IMHA at all, they just buy us some time to start immunosuppressive therapy.

There are no large scale blood banks for pet blood so we often have to take blood fresh from a donor. This makes transfusions labour and resource intensive and therefore fairly expensive.

 

immunosuppressive therapy

Corticosteroids are the cornerstone of immune suppression. Prednisolone is the most commonly used oral therapy – it is directly toxic to immune cells called lymphocytes, which are the ones that produce antibodies. If the red cells stop being tagged by antibodies, they stop being removed from the circulation.

Corticosteroids also suppress the activity of the cells that remove the red cells with antibodies stuck to them.

High doses are used at first. This will cause side effects (eg excessive thirst and urination, panting, hunger, gastric ulceration, appearance of a pot belly, thinning skin). We just have to accept these in order to try and fight the life-threatening disease. Over time, if we are seeing a good response, we'll slowly reduce the dose and the side effects will lessen. If we stop therapy too soon, the haemolysis will start up all over again. You can expect many months of treatment. For some patients, treatment will be life long.

In many cases (particularly if autoagglutination is present), we use additional immunosuppressive therapy such as azathioprine. This takes longer to work than prednisolone, but works synergistically with it and can reduce the side effects by allowing us to reduce the dose more readily. Note that aza

Sometimes, no matter how hard we work to suppress the immune system, the disease rages on out of control.

 

Anti-clotting medication

While clotting is a serious component to IMHA, we can run into issues using anti-clotting medications. Options include heparin (which is only used in hospital), low-dose aspirin and clopidogrel. None have been shown to definitively improve survival but can increase the risk of gastric ulceration and bleeding.

 

Monitoring response to treatment

During treatment we're monitoring three main things:

  • if the immune suppression therapy is working – we do this by rechecking the red cell level 
  • if we have symptoms of blood clots
  • if we have serious side effects that require treatment or medication change

It may take weeks to months to get IMHA under control.