Cancer and anaemia

Written by Dr Dan Rutherford, GP and Dr Rachel Green, consultant haematologist and clinical director of the Glasgow and West of Scotland Transfusion Centre

Introduction

Anaemia is a general term meaning a lack of red blood cells in the circulation and there are many possible ways in which anaemia can arise. As red cells have the job of transporting oxygen around the body, anaemia is one of the common causes of breathlessness and tiredness.

Cancer is a general term for malignant tissue no matter of which type or location in the body. Cancer can give rise to anaemia by various routes - due to the direct effects of the cancer cells in the body, or as a result of biologically active products of the cancer cells or even as a consequence of the treatment of cancer.

The mechanisms behind cancer-related anaemia can be understood by looking at the main ways in which all anaemias occur.

Types of anaemia

Broadly speaking, anaemias are of two types:

those in which red cells are lost too quickly, for example a) from bleeding, especially when this has gone on for some time or b) where the red cell is more 'fragile' and therefore has a much shorter life span.

those in which the red cells are not manufactured properly in the bone marrow. This might be due to disease of the bone marrow itself, or to a lack within the body of the 'building blocks' of blood, such as iron or certain vitamins, so that the process of blood cell manufacture is impaired.

Quite often more than one type of cause will be present at the same time.

Anaemia from blood loss

Some tumours, particularly of the digestive system, can bleed so slowly that the bleeding itself may not be obvious. If it continues over a long period of time then eventually the person becomes anaemic and goes to the doctor feeling tired.

This happens if the rate at which blood is lost is faster than the body's ability to replace the red blood cells. Healthy bone marrow produces the equivalent of about 20ml of fresh blood daily - over 70 litres per year - to replace the normal needs of the body.

The limiting factor in long-standing blood loss is usually the availability of the raw materials for the bone marrow to work with rather than the capacity of the bone marrow to respond. Iron is an important component of the oxygen-carrying molecule called haemoglobin, which is contained within the red cells and a lack of iron therefore holds back the production of new, properly formed red cells.

Anaemia due to iron deficiency is the characteristic finding with a cancer of the colon (large bowel), stomach or gullet. Often the anaemia is the only clue to the presence of a bleeding source somewhere. Any person who develops iron deficiency anaemia with no obvious cause should be investigated for the presence of a bleeding point within the digestive system. Fortunately not all bleeding sources turn out to be cancers.

Of course any source of regular or prolonged bleeding can possibly cause iron deficiency, so a check should also be made for blood loss in the urine or, in a woman, from the womb although both of these sources are more likely to cause obvious blood loss.

As we depend on the iron in our diet to supply us with our needs, iron deficiency anaemia will occur more quickly if a person's intake is poor for any reason or the quality of their diet is unsatisfactory.

For example, someone with a tumour of the gullet or stomach might have difficulty swallowing a normal diet, so a supplement of vitamins or minerals is sometimes necessary to add to what they can take. Cancer can be associated with reduced appetite, which can add to a person's nutritional difficulties.

Anaemia due to bone marrow failure

The bone marrow has a rich blood supply, and is the site of manufacture of all blood cells. If a cancer in one part of the body sheds some cancer cells in to the circulation, which is often the way cancers spread (metastasis), there is a good chance that the circulating cancer cells will enter the bone marrow and lodge there. The bone marrow is therefore a common site for a metastasis to develop. Cancers of the breast, prostate and lung are the commonest type to do this although almost all cancers have this capability.

Once in the marrow the cancer cells can multiply easily, being well supplied with blood. The tumour deposit enlarges, occupying more and more of the marrow space, so reducing the amount of blood-producing marrow. It does require a large amount of marrow to be replaced with tumour for this alone to be the cause of anaemia, as the bone marrow has a fair amount of reserve capacity. However, someone who has widespread metastasis will usually be in the advanced stage of a cancer, in which the body's metabolism seems to be impaired for reasons that we do not yet fully understand. In such circumstances anaemia is more likely to occur.

There are some tumours that arise from the bone marrow tissue itself, such as some types of leukaemia and multiple myeloma. (link) As these are more directly involved with the bone marrow's function they are more commonly associated with anaemia.

The effect of cancer treatment

One of the main features of cancer cells is that they multiply more rapidly than normal cells, and this exposes a weakness of cancer cells, which is exploited by anti-cancer treatment.

The genetic information within every cell is held within the chromosomes of the nucleus - this is where the cell's DNA is stored.

To reproduce, a cell basically splits in two, and in this process the chromosomes must copy themselves and then divide into two, providing each new cell with a complete set of chromosomes. This is a complex process, involving many steps and most forms of cancer treatment take advantage of the fact that the dividing cell is vulnerable to interference with this copying process.

Cancer drugs are designed to block the copying of the cell's chromosomes, which therefore prevents the cell from multiplying.

Unfortunately it is extremely difficult to produce a cancer drug that will only block the multiplication of cancer cells and leave normal cells alone. Cell duplication is a normal process - it is part of the body's continual repair and renewal of old and damaged cells - and so an inevitable consequence of cancer treatment is that normal cells are damaged too.

This effect is most obvious in tissues that normally have a high rate of renewal. Hair is a good example - we grow hair all the time and hair loss is often seen during cancer treatment. Bone marrow is also a very active tissue, and cancer treatment can sometimes be very hard on normal bone marrow, causing anaemia. As the bone marrow manufactures all of the blood cells, including the white cells we need to fight infections, a person receiving cancer treatment can also be more prone to infections if their white cell count drops too low.

Drug treatment (chemotherapy) is the most likely to cause anaemia in this way, particularly with drugs of the 'platinum-containing' type (such as Carboplatin or cisplatin). Other forms of cancer treatment, such as X-rays (radiotherapy) can have a similar effect upon the bone marrow.

Fatigue and cancer

Fatigue is a significant cause of disability in cancer patients and anaemia is only one possible cause. Depression and lack of sleep for example may cause significant fatigue if they are not recognised and treated. The main aim of palliative care for cancer patients (and for any significantly disabling condition) is to improve the quality of life for the individual and if someone with cancer has fatigue then a cause should be sought, and corrected when feasible.

Treatment of cancer-related anaemia

The primary aim is of course to find the cause of the anaemia and correct it if possible. A bleeding tumour of the bowel may give rise to iron deficiency anaemia and the anaemia might respond to iron tablets, but a true cure requires the removal of the bowel cancer.

Where the anaemia does not have a directly curable cause then two important treatments exist - blood transfusion and erythropoietin therapy.

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