Thrombocytopenia (reduced platelet count)

Written by Dr Claire Harrison, Consultant Haematologist, St Thomas' Hospital, London and Professor Samuel Machin, Department of Haematology, University College London Hospital

Congenital thrombocytopenia
Several rare inherited diseases cause low platelet counts. The severity of the thrombocytopenia varies with the condition and also the individual patient.

In some of these conditions, eg May Hegglin anomaly, bleeding doesn't happen often.

In other inherited diseases, eg Bernard Soulier syndrome, the platelets function less well and lifelong bleeding symptoms can occur.

Defective platelet production
Platelets are produced within the bone marrow from cells called megakaryocytes.

If there is a problem in the bone marrow, for example due to abnormal cells, then the number of megakaryocytes will drop, lowering the number of platelets that can be produced.

Examples of abnormal cells accumulating in the bone marrow include:

acute leukaemia where leukaemic cells, or 'blasts', are seen

other abnormal cancer cells such as lymphoma

more rarely, when cancers develop in another part of the body and have spread (metastasised) to the bone marrow.

Alternatively, there may be something wrong with the platelet production process itself so not enough platelets are formed.

Impaired platelet production can also be due to:

the side-effects of drugs such as chemotherapy (anti-cancer) agents

viral infections such as HIV

metabolic disorders such as shortage of vitamin B12 or folic acid, kidney failure, alcohol.

an abnormality of the bone marrow called myelodysplasia.

Sometimes platelet production is defective because of an abnormality in the cells that make up the structural parts of the bone marrow, called the stroma. Examples include:

marble bone disease (osteopetrosis). This hereditary condition causes dense, brittle bones at the expense of bone marrow.

myelofibrosis. This causes a massive increase in the amount of fibrous tissue, which impairs platelet production as well as the production of other blood cells.

Diminished platelet survival
Platelet numbers fall if they are removed from the circulation more rapidly than they are produced.

Platelets are removed for several reasons. They may be coated with an antibody, or are clumped together and then removed.

Antibodies that cause platelet removal can be due to:

infections such as HIV

medicines such as the anti-malaria drug quinine

a specific disease in which abnormal production of other antibodies may occur, eg rheumatoid arthritis, the skin disease systemic lupus erythematosis or the blood disease chronic lymphocytic leukaemia.

These antibodies can also occur in someone who is otherwise completely well. This is called idiopathic thrombocytopinea (ITP) - literally, a low platelet count of unknown cause.

Alternatively, the platelets may be used up if the blood clotting process is inappropriately 'switched on'. This condition is known as disseminated intravascular coagulation (DIC).

DIC can result from the following:

in severe infections such as meningitis.

as a complication of pregnancy or labour, eg high blood pressure and pre-eclampsia

in some cancers, specifically types of acute myeloid leukaemia and prostate cancer

in some rare blood disorders such as thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome (sometimes due to food poisoning outbreaks).

Loss of platelets from the circulation

Abnormal distribution of platelets: a low platelet count may be due to a build up of platelets outside the normal blood pool, for example in a patient with a very large spleen.

Dilution of platelets: the platelet count can fall when a patient is transfused with a large volume of red blood cells that do not contain platelets, because of dilution of normal blood factors.

How is a low platelet count diagnosed?
Investigation usually starts with a history of symptoms, signs of bleeding or bruising, other medical problems, recent infections and medications. A blood test is then taken.

In the haematology lab the doctor:

performs a full blood count

examines the blood film under a microscope (see Figure 1)

examines the blood sample in the test tube.

Usually, another full blood count sample is requested to confirm the result and see if it is a persisting abnormality.

Depending upon the severity of the platelet lack and the likely cause, the person is likely to be referred to a haematologist at the hospital.

If the platelet count is very low, the person may need to be seen on the same day, and have a bone marrow test performed.

A bone marrow test is done under local anaesthetic, with samples usually taken from the back of the pelvis.

This test helps the haematologist to decide if platelets are being produced normally and whether the rest of the bone marrow appears normal.

Further tests such as genetic tests can also be done on a bone marrow sample.

What treatment is available?
The choice of treatment depends upon the severity of the platelet count, its cause and whether or not there is any bleeding.

Caution In a type of thrombocytopenia called TTP, the use of platelet concentrates is hazardous.

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