The different causes of a low platelet count are described below.

Artefactual thrombocytopenia

Some people have platelets that stick together due to the presence of proteins in the blood (antibodies) that bind to the platelets. These antibodies, which are formed by the immune system of the body also bind to a chemical in blood that is tested in test tubes, giving a falsely low platelet count. So it can be helpful to repeat the sample in different tubes with different chemicals. The platelet count can also be reduced if the blood sample is difficult to take and the blood clots - thus using up some of the platelets.

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 does not often occur, whereas in other inherited diseases, eg Bernard Soulier syndrome, the platelets function less well and lifelong bleeding symptoms can occur.

Impaired platelet production

Platelets, as with the rest of the blood cells, are produced within the bone marrow and the cells from which platelets originate are called megakaryocytes. If there is a problem in the bone marrow, for example because of a build-up of abnormal cells due to some other reason, then the number of megakaryocytes will be reduced, thus 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, and other abnormal cancer cells such as lymphoma, or more rarely cancers developing in another part of the body (such as the breast or prostate gland) which have spread (metastasised) to the bone marrow.

Alternatively the platelet production process may be abnormal and so although the number of precursors may be normal, adequate numbers of platelets are not produced. Impaired platelet production can also be due to the toxic side effects of drugs such as chemotherapy (anti-cancer) agents, alcohol, or viral infections, such as HIV, or due to an abnormality of the bone marrow called myelodysplasia.

Sometimes platelet production may be impaired due to an abnormality of the bone marrow cells which are not involved in blood production, but make up the structural parts of the marrow (called the 'stroma'). An example of this is the inherited condition called marble bone disease, or osteopetrosis, where increased bone formation occurs at the expense of bone marrow.

A similar but not inherited condition called is characterised by massively increased fibrous tissue, which impaimyelofibrosisrs platelet production as well as the production of other blood cells.

Increased platelet destruction

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, or they may not be removed but are used up by a condition in which the blood clotting process is inappropriately 'switched on' called disseminated intravascular coagulation (DIC).

DIC can happen in several different conditions, including 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) and in some rare blood disorders such as thrombotic thrombocytopeniapurpura or the haemolytic uraemic syndrome (sometimes due to food poisoning outbreaks).

Antibodies that cause platelet removal can be due to infections such as HIV, or to the presence of drugs - eg the anti-malaria drug quinine. Sometimes antibodies causingthrombocytopenia arise in a patient with a specific disease in which abnormal production of other antibodies may occur. These include so-called autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosis, or the blood disease chronic lymphocytic leukaemia. But the antibodies can also occur in someone who is completely well - known as idiopathic or unknown cause.

Abnormal distribution of platelets

Thrombocytopenia may be due to a build up of platelets outside the normal blood 'pool', eg in a patient with a very large spleen.

Dilution of platelets

When a patient is massively transfused with a large volume of red blood cells, which do not contain platelets, the platelet count can fall because of dilution of normal blood factors.

These different causes of thrombocytopeniaare not mutually exclusive and more than one may be responsible for an abnormal platelet count. For example, platelet production may be impaired in a baby deprived of oxygen at birth, but these babies are also susceptible to infections that might cause worsening of thrombocytopenia due to DIC.

A summary of the causes of thrombocytopeniais provided below.

Artefactual (false) thrombocytopenia

• Clot in the sample.
• Platelets clumped.

Congenital thrombocytopenia

Defective platelet production

• Bone marrow aplasia (failure).
• Metabolic disorders (shortage of vitamin B12 or folic acid, kidney failure, alcohol).
• Abnormal platelet precursors (viral infections, inherited abnormalities).
• Abnormal bone marrow (preleukaemia).
• Bone marrow infiltration (leukaemia, lymphoma, myeloma, marble bone disease).

Loss of platelets from the circulation

• Massive or exchange transfusion (dilution).
• Enlarged spleen (abnormal distribution).

Diminished platelet survival

• Immune mediated (antibodies due to drugs, blood transfusion, another autoimmune disease, or idiopathic [ITP]).
• Other mechanisms (malaria, glandular fever, AIDS, drugs).
• Disseminated intravascular coagulation (DIC).
• Thrombotic thrombocytopenic purpura.
• Leaking artificial heart valves.