The blood disorder that is particularly characterised by a high platelet count is primary thrombocytosis (PT), also called essential thrombocythaemia (ET) and it is this condition that we will now focus on in more detail.

ET is one of the MPDs in which the major feature is a thrombocytosis; when the bone marrow is examined there is an increase in the platelet producing cells, the megakaryocytes (see Figure 1). Some people with ET can suffer from bleeding or clotting due to their disease but others have no symptoms at all. ET is usually diagnosed in people aged 60 years and above, but it appears to be becoming more common in people under 40 years of age - particularly in women. This may be as a result of more sophisticated blood cell counters becoming available in the past 20 years that are able to automatically count platelets and so make the diagnosis more often. It has been estimated that one person in about every 100,000 to 150,000 will be diagnosed with ET every year.

Patients with ET are at increased risk of both clotting and bleeding events. Although the incidence of these complications varies, these differences probably relate to the fact that ET is a rare disorder, and that the medical literature is based on relatively small numbers of affected people.

Symptoms are present at diagnosis in 40-90 per cent of cases - ET being diagnosed coincidentally in the remaining patients. Table 2 shows a list of some of the clotting and bleeding problems that may occur more often in patients with ET. The natural history of ET includes a relatively uncommon tendency for the development of acute leukaemia, usually acute myeloid leukaemia and a stiffened marrow with reduced cell production and an enlarged spleen known as myelofibrosis (MF). The risk of developing acute leukaemia is increased by some of the drugs used in treatment of ET. Both acute leukaemia and MF are difficult to treat. The leukaemia is unfortunately often more resistant to drugs used in its treatment and MF may require regular transfusion as well as removal of the usually very enlarged spleen.

These complications, in particular clotting (medically termed 'thrombotic') episodes, are the major cause of ill health in patients with ET and they also have a significant impact on survival. Bleeding, or haemorrhage, can appear in a variety of forms from easy bruising or nosebleeds, to more sinister bleeding from the gut and, fortunately rarely, in the head. Haemorrhagic complications in ET are less common than thrombotic ones and as a result have proven difficult to study - they are less likely to occur if the platelet count is less than 1000 million per ml. It is not usually possible to predict their occurrence by looking at the function of platelets taken from the patient despite the sophisticated tests available to do this. In some ET patients with markedly elevated platelet count in excess of 1500 million per ml there is an increased risk of bleeding due to the platelets affecting a protein known as von Willebrand factor, which is important for normal clotting.

Thrombotic or clotting events in ET are more common and to a certain extent we are more able to predict whether they will happen or not. The two most important risk factors for these events are:

• age over 60 years
• having had a thrombotic complication already.

A 60-year-old has a 10-15 fold more chance than a patient under 40, and a previous event increases the risk by almost 10 times. A variety of risk factors for arterial vascular disease, for example hypertension, cigarette smoking, diabetes and probably also high cholesterol will influence the chance of a thrombosis affecting the arteries. There are a number of well-defined conditions that predispose to so-called venous thrombosis for example deficiencies of proteins C, S, antithrombin III, Factor V Leiden mutation and antiphospholipid antibodies. The added contribution of these factors to thrombotic complications in ET has not been defined.

Fortunately we know that we can reduce the chance of both the bleeding and clotting complications of ET by treatment with drugs to reduce the stickiness of the platelets and, in some patients, drugs that will reduce the platelet count.