Monday, March 10, 2014

Three things I learned: anaemia in the cancer patient

Randy loves his new Timothy Hay house. Its nothing to do with anaemia in oncology patients, but its a little dose of happiness at the beginning of the week.
Aloha Monday! Last week SydneyUniversity oncologist Peter Bennett presented a fantastic overview on anaemia in the cancer patient. (For those who don't know, we're currently enrolled in the Centre for Veterinary Education Distance Ed oncology program, taught by Dr Bennett. I highly recommend it).

[If you don't feel like reading about anaemia in oncology patients, here's another pic of Randy].

A timothy-hay house acts simaltaneously as a shelter and a snack.
Cushing enjoys the house too.
Anaemia is a problem in cancer patients for a range of reasons. It is associated with a poorer overall prognosis, as well as poor wound healing, decreased appetite (especially in cats), increased anaesthetic and surgical risk and increased risk of toxicity associated with chemotherapy or radiation. The aim is to avoid it, or recognise and treat anaemia where necessary.

The most important thing I learned (well, I knew it but it was reinforced) is that cancer patients develop anaemia for a variety of reasons which can be categorised under:

  1. Decreased production of red blood cells (this is the most common form)
  2. Increased loss
  3. Increased destruction

Decreased production
Anaemia of chronic disease is the most common form of decreased production in the cancer patient and is usually mild. It usually causes a non-regenerative, normocytic, normochromic anaemia.

Myelophthisis (bone marrow suppression due to marrow infiltration by tumour cells with local production of myelosuppressive cytokines) is more common in dogs than cats, and tends to be seen with lymphoid tumours and leukaemias. This can vary from mild to severe. Red blood cells are often the last cell line to decrease, with thrombocytopaenia often occurring in the early stages. It causes a non-regenerative, normocytic, normochromic anaemia, as does chemotherapy associated anaemia.

Iron deficiency anaemia is uncommon but usually secondary to gastrointestinal or external blood loss that is ongoing and severe. It causes a non-regenerative, microcytic, hypochromic anaemia.

Increased loss
This is most common with vascular tumours such as Haemangiosarcoma and haemangiomas. Any splenic tumour has a very high risk of bleeding and most have at least one haematoma associated with them. Hepatic tumours can also bleed. Clinical signs can be cyclical as the animal has an internal bleed then autotransfuses over 3-4 days, hence they can appear weak and lethargic and bounce back. Autotransfusion itself can cause red blood cell changes, e.g. schistocytes.

Initially animals with anaemia secondary to vascular tumours will have a non-regenerative, normocytic, normochromic anaemia, but over time this can become regenerative, with macrocytosis, polychromasia an reticulocytosis (though autotransfusion can blunt the regenerative response).

Blood loss commonly occurs in the GIT, with epithelial tumours bleeding the most. Melena is not always seen or recognised by owners. Around 5-10 per cent of dogs with mast cell tumours will have gastrointestinal ulcers, but significant bleeding will only occur in a fraction of these. Other potential causes of GI ulceration include gastrinomas, renal failure and liver failure (lymphoma a common culprit). Animals with nasal tumours may swallow blood, so epistaxis isn’t always present. It can be tricky in some cases to differentiate nasal from gastrointestinal bleeding.

Usually the signs of the tumour will predominate over signs of anaemia – for example, with GIT tumours, the predominant signs will be vomiting, diarrhoea and weight loss. These animals may have a moderate to severe hypoproteinaemia.

Primary and secondary coagulopathies can occur. Immune mediated thrombocytopaenia is often associated with lymphoma. Dogs with haemangiosarcoma are at increased risk of disseminated intravascular coagulation (DIC) – strangely enough DIC (or IC at any rate) can be localised to the spleen. Mast cell tumours produce anticoagulant factors such as heparin.
The anaemia is usually regenerative.

Increased destruction
The main causes in cancer patients are immune-mediated haemolytic anaemia (IMHA), microangiopathic haemolytic anaemia and erythrophagocytosis.

IMHA is a common cause of severe anaemia in cancer patients and is most often associated with lymphoid malignancies. The aetiology is not fully understood but it might be due to altered immune function or the presence of surface antigens on tumour cells that are shared by red blood cells. It usually causes regenerative anaemia. Quite often in these cases the animal will present for signs of anaemia and the cancer is discovered during work up, rather than the other way around.

Microangiopathic haemolytic anaemia is most often seen with vascular tumours such as haemangiosarcomas, but it can be seen with lymphoma. Red cells cop a beating when they pass through vascular channels containing fibrin strands, and these damaged cells are removed by the spleen. Dr Bennett said there is probably also an immune-mediated component. There is a regenerative anaemia, often with signs of erythrocyte damage e.g. schistocytes.

Erythrophagocytosis is seen with the aggressive form of histiocytic sarcoma. Bernese Mountain Dogs are over-represented here. As the name suggests, the cancer cells actually phagocytose (eat) red blood cells. It causes a severe regenerative anaemia.

What do you do about it?

The trick can be working out which kind of anaemia the patient has. Small tumours can be associated with severe anaemia and large tumours can be associated with mild anaemia – or vice versa. The presentation of the animal depends on the tumour type, stage and grade.

Obviously the first step is to identify anaemia (low haematocrit and haemoglobin), but also find out in the history whether onset is acute or chronic. Have there been signs of lethargy, pallor, weakness, exercise intolerance, reduced appetite, dyspnoea? For how long? Have there been episodes of external blood loss?

Signs to look for on physical exam include obvious signs of external haemorrhage, a fluid wave, muffled ventral lung/heart sounds, pallor or signs of coagulopathy. Mast cell tumours may be associated with gastric ulceration, so cutaneous tumours can be an important clue in the work up of anaemia.

A rectal exam should be performed to check the faeces and rectal mucosa for blood. I knew that recent (ie within 4 days) ingestion of meat could interfere with occult faecal blood test results – but ingestion of green vegies in the same time period can also give a false result.

A CBC/MBA and UA should be performed, but its always important to perform a blood smear for morphological evaluation.

Treatment of anaemia depends on the severity and the underlying cause. Ideally, we diagnose and eliminate the underlying cause (for example, remove the bleeding tumour). Other treatment may include blood or platelet rich plasma transfusion, oxygen, rest, gastroprotectants, vitamin K, withdrawal of certain drugs from the treatment regime or immunosuppression – depending on the particular case.

Withdrawal of chemotherapy drugs should be carefully considered as it brings the risk of disease relapse. Use of an alternate agent can be considered although it is likely to have similar effects, or EPO can be given (though Dr Bennett doesn’t feel this really helps in most cases).