Aplastic Anaemia

Aplastic anaemia only affects about 120 – 150 people each year in the UK.

Although it can affect anyone, at any age, it is most common between 10 and 20 years old and in people aged over 60 – 65 years old.

There is strong evidence that the damage to stem cells in the bone marrow is started by the patient’s own immune system attacking itself and that the patient’s own T-lymphocytes are responsible for this. When the immune system attacks the body’s own cells, this is called an auto immune reaction. This immune-mediated destruction of the stem cells can occur following a viral infection or following exposure to certain environmental toxins or chemicals. AA also happens in people with inherited genetic mutations in the genes that control blood cell production. More often than not, however, a defined cause for these auto-immune events is never identified.

The symptoms of AA are not caused by damage to stem cells but by the lack of normal blood cells. The most common symptoms are those of anaemia or of bleeding due to low platelet counts but infection may also be a symptom at diagnosis, especially if the neutrophil count is very low.

• Anaemia due to lack of red blood cells – weakness, tiredness, shortness of breath, light-headedness, palpitations.
• Bleeding and bruising due to lack of platelets – purpura (small bruises in the skin), nosebleeds, bleeding gums, vision problems (bleeding in the retina). Severe bleeding is not common but requires urgent treatment.
• Infections due to lack of white blood cells – infection may be a significant problem at the time of diagnosis. Severe infection requires urgent treatment.

There is no single test that reliably diagnoses acquired AA and the diagnosis is one of exclusion. All alternative causes of bone marrow failure must be excluded as part of the diagnostic evaluation. Tests required to achieve this include:

• Full blood count – This is a routine blood test which measures the number of red cells, different types of white cells and platelets in the blood.
• A blood film examination – The blood is smeared on a microscope slide, allowing the blood cells to be examined under the microscope. In many patients with acquired AA, the number of red blood cells, neutrophils and platelets are decreased; however, the number of lymphocytes are usually normal.
• Bone marrow biopsy – The bone marrow sample can be taken from the hip bone under local anaesthetic, using special biopsy needles: liquid bone marrow (aspirate) and a tiny core of bone marrow tissue (trephine). A bone marrow biopsy is mandatory for a diagnosis and will show an empty or sparse marrow which usually contains fat cells.
• Tests for gene mutations – Blood or bone marrow tests may be performed to check for mutations to exclude inherited AA and also somatic (acquired) mutations related to the patient’s external causes. Somatic mutations are acquired, non-inherited mutations which are related to environmental factors. In acquired AA, the most common somatic mutations can be found in the following genes:
  • PIGA (phosphatidylinositol glycan class A)
  • ASXL1 (additional sex combs like 1)
  • BCOR (BCL6 corepressor)
  • DNMT3A (DNA [cytosine-5]-methyltransferase 3 alpha)

Classification of acquired aplastic anaemia

The classification is based on how low the numbers of blood cells have fallen, which can be found out by a blood count.

To make a diagnosis of AA, at least two of the following must be present:

• Haemoglobin less than 100g/L
• Platelet count less than 50 x 10⁹/L
• Neutrophil count less than 1.5 x 10⁹/L

AA is classified as non-severe, severe or very severe.

Non-severe aplastic anaemia

This meets the above criteria for aplastic anaemia but does not meet the criteria for severe or very severe aplastic anaemia.

Severe aplastic anaemia 

Hypocellular bone marrow and any two of the following:

• A low platelet count (less than 20 x 10⁹/L)
• A reticulocyte count less than 20 or 60 x 10⁹/L
• A neutrophil count less than 0.5 x 10⁹/L

Very severe aplastic anaemia

Hypocellular bone marrow and any two of the following:

• A low platelet count (less than 20 x 10⁹/L)
• A reticulocyte count less than 20 or 60 x 10⁹/L
• A neutrophil count less than 0.2 x 10⁹/L

The difference between severe and very severe AA is how low the number of neutrophils falls; which increases the risk of severe infection.

Hypocellular bone marrow is defined as bone marrow cells <25%, or 25-50% with less than 30% of stem cells in your bone marrow.

The classification is based on how low the numbers of blood cells have fallen, which can be found out by a blood count.

To make a diagnosis of AA, at least two of the following must be present:

• Haemoglobin less than 100g/L
• Platelet count less than 50 x 109/L
• Neutrophil count less than 1.5 x 109/L

AA is classified as non-severe, severe or very severe.

Non-severe aplastic anaemia

This meets the above criteria for aplastic anaemia but does not meet the criteria for severe or very severe aplastic anaemia.

Severe aplastic anaemia

Hypocellular bone marrow and any two of the following:

• A low platelet count (less than 20 x 109/L)
• A reticulocyte count less than 20 or 60 x 109/L
• A neutrophil count less than 0.5 x 109/L

Very severe aplastic anaemia

Hypocellular bone marrow and any two of the following:

• A low platelet count (less than 20 x 109/L)
• A reticulocyte count less than 20 or 60 x 109/L
• A neutrophil count less than 0.2 x 109/L

The difference between severe and very severe AA is how low the number of neutrophils falls; which increases the risk of severe infection.

Hypocellular bone marrow is defined as bone marrow cells <25%, or 25-50% with less than 30% of stem cells in your bone marrow.

If you have non-severe acquired AA, you may not require any treatment initially and a watch and wait approach is often recommended at first. Watch and wait usually involves regular check-ups and blood tests, as well as advice on how to maintain a healthy lifestyle. Your medical team will discuss your treatment options with you. As well as the severity of your acquired AA, your age, general health and availability of a bone marrow donor are important considerations for the selection of treatment.

For all patients with acquired AA, the possible cause of the acquired AA should always be sought, particularly in the case of a drug the patient may be taking or exposure to fertilizers or pesticides. The suspected cause should be removed immediately.

Treatment of patients with acquired AA is aimed at:

• Replacing or renewing the depleted stem cell pool (such as with stem cell transplantation)
• Controlling the damage to bone marrow stem cells (immunosuppressive and anti-thymocyte therapy)
• Stimulating the remaining bone marrow stem cells
• Providing supportive treatment for anaemia, bleeding (blood transfusions) or infections (antibiotics or antifungal drugs)

The guidelines for acquired AA recommend allogeneic stem cell transplantation (Allo-SCT) or immunosuppressive therapy (IST) comprising of anti-thymocyte globulin (ATG) with ciclosporin (CsA) as initial treatment for acquired AA patients.

This treatment involves the use of the drugs to control the activity of the immune system and reduce the damage being done to bone marrow stem cells. This is the preferred treatment for patients with non-severe AA and for patients with severe or very severe AA who are over 35-50 years old or not able to have a stem cell transplant.

The most widely used combination is an antibody called anti-thymocyte globulin (ATG) combined with a drug called ciclosporin (CSA). This is successful in around 70% (two thirds) of patients.

If you have received immunosuppressive treatment, you should not have any vaccinations, including the annual flu vaccination This is because there is a theoretical risk that vaccinations might cause your AA to return.

If you need a transfusion during or after immunosuppression treatment, it is important that you should be given irradiated blood cells. This will protect against a possible reaction called transfusion-related graft vs host disease (GVHD is a rare complication that develops 4 – 30 days after a blood transfusion).

For younger/fitter patients who have a fully-matched sibling, a donor stem cell transplant is the first treatment of choice. This involves doses of chemotherapy and an antibody to suppress the body’s immune cells so that they don’t reject the new stem cells followed by a transplant of healthy stem cells from the donor. The treatment is reported as offering a 75% – 90% chance of long term cure.

If you have received a stem cell transplant, you should receive all your recommended vaccinations as normal.

If you need a transfusion after a stem cell transplant, it is important that you should be given irradiated blood cells. This will protect against transfusion-related GVHD.

We understand going through a blood cancer journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your doctor.

• How would I know if I had AA?
• What tests will I need to have?
• What will the tests show?
• How long will the results take?
• How rare is AA?
• What sort of treatment will I need?
• How long will my treatment last?
• What will the side effects be?
• Is there anything I should or shouldn’t eat?
• Will I be able to go back to work?
• Where can I get help with claiming benefits and grants?
• Where can I get help dealing with my feelings?

We have free patient information available for AA patients.

You can download the booklets on our information pages here.

Alternatively, you can have the information delivered free of charge by requesting it through our resources page. 

Sarah Cheeseman was diagnosed with aplastic anaemia in 2007, read her story here.

The Aplastic Anaemia Trust is the only charity in the UK dedicated solely to research into aplastic anaemia and allied rare bone marrow failures. They also provide practical information and advice to patients and their families as well as peer-to-peer support.

For further information on the latest research and to access information and support, please contact The AAT via their website www.theaat.org.uk