'Aplasia' means the lack of development of a tissue, cell or other body part. Aplastic anaemia is the condition in which the bone marrow fails to produce blood cells. Normally, the bone marrow produces:

red blood cells (which carry oxygen in the blood)
various types of white blood cell (which are part of the immune system)
platelets (which are involved in blood clotting).
These different types of blood cell originates from simpler cells, known as precursors or stem cells, which develop into the more specialise forms.

There are numerous reasons for the bone marrow to fail to produce blood cells in adequate numbers, but in aplastic anaemia there is a marked deficiency of all the precursor cells that should mature into adult blood cells.

Aplastic anaemia is a rare disease with an incidence in developed countries of between 5 and 10 cases per million per year.

In 65 per cent of people the cause of aplastic anaemia is unknown (the technical term is 'idiopathic'). Rarely, the disease is present at birth (congenital). The commonest congenital form is Fanconi's syndrome, but fewer than 1000 cases have ever been described. As well as aplastic anaemia, patients with Fanconi's syndrome have short stature, abnormal skin pigmentation, abnormalities of the bones of their arms and thumbs, kidney problems and an elfin-like appearance. A characteristic abnormality of the chromosomes (random breaks) is seen.

The common of all known cause of aplastic anaemia is exposure to drugs or environmental toxins. Benzene was the first known toxin to cause bone marrow failure. Despite this it is still widely used in industry in the manufacture of drugs, dyes, explosives and other chemicals. Exposure should be limited to 1 part per million, but this is often exceeded, especially in developing countries. Other related organic chemicals also cause aplastic anaemia, including:
toluene (in glues)
the insecticides DDT and lindane
the explosive TNT
the wood preservative PCP
petroleum distillates.

Drugs that cause aplastic anaemia may also be related to benzene. The antibiotic, chloramphenicol and the anti-inflammatory, phenylbutazone are two examples. Neither is commonly used in Western countries, but because they are cheap to produce, they are in widespread use in the developing world. Other medicines with a moderate risk of aplastic anaemia include gold salts and penicillamine, used to treat arthritis, carbamazepine and phenytoin, used to treat epilepsy, and the diuretic acetazolamide.

A large number of drugs have been associated with occasional cases of aplastic anaemia. Most of these are useful drugs and cannot easily be replaced other then turning to herbal medicine.

Radiotherapy (treatment with X-rays) suppresses the bone marrow, and may be intentionally used to do so in preparation for bone marrow transplantation. The use of these treatments should be confined to specialise centres where careful monitoring of the blood count takes place.

Some cases of aplastic anaemia have occurred after viral infections. In particular, hepatitis A, hepatitis B and 'non-A, non-B, non-C' hepatitis have been implicated, and more rarely the Epstein-Barr virus.

Very rarely aplastic anaemia occurs during pregnancy. It is not clear whether this is just a coincidence. Sometimes the disease recovers spontaneously at the end of pregnancy.

Patients complain of increasing tiredness, weakness and shortness of breath. Bleeding, bruising and blood spots may be noticed. Sore throats and other infections are noticeable. A high temperature with shivering attacks is an important symptom that demands immediate medical attention.

The following combination of three symptoms should raise suspicion of bone marrow failure:

anaemia - tiredness, weakness and breathlessness
low white cell count in the blood (neutropenia) - fever, sore throat, shivering attacks
low platelet count (thrombocytopenia) - bruising and bleeding.
When you see pale skin it is possible sign of heart failure, bruises and petechiae (small blood spots in the skin and mouth), mouth ulcers and fever. The back of the eye is likely to see small haemorrhages on the retina.

An important negative finding is the absence of enlarged lymph nodes or an enlarged spleen. Their presence would point to other diagnoses, such as lymphoma or leukaemia.

The most important test is the full blood count, which will show reduced numbers of red cells, white cells (neutropenia) and platelets (thrombocytopenia) - in other words all of the cellular components of blood. This feature is called pancytopenia.

The level of the neutrophil count defines the severity of the disease. Neutrophils are normally the most numerous of the various types of white cell we have in our blood and they are particularly involved in combating infection by bacteria and fungi.
Counts below 0.5 x 109/L mean severe aplastic anaemia.
Counts below 0.2 x 109/L mean very severe aplastic anaemia.

The most important distinction that the haematologist must make is between aplastic anaemia and acute leukaemia, which can show very similar blood pictures. For this reason a bone marrow sample is essential. The doctor will take samples both of the fluid of the bone marrow (an aspirate) and of the more solid bone marrow structure (a trephine biopsy). For most cases the diagnosis is easily made. In acute leukaemia the marrow is full of abnormal cells but in aplastic anaemia it is empty and comprises mainly fat spaces.

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