The myeloproliferative disease, primary thrombocythaemia (PT), has a median age of presentation of 60 years but is increasingly being recognised at an earlier age. The risks of the untreated condition are micro-vascular and major vessel occlusive events and haemorrhage. Older patients and those with a previous thrombosis are particularly prone to experience a significant vascular occlusive event. An anti-aggregating agent, such as aspirin, has been shown to reduce/alleviate minor ischaemic symptoms. Therefore, except in patients with haemorrhagic symptoms, peptic ulceration and known side-effects to aspirin, the use of low-dose aspirin is appropriate.

Myelofibrotic and acute leukaemic transformations can be long-term complications of PT. The ability of therapeutic agents to delay myelofibrosis or reduce/increase the incidence of acute leukaemia in prospective studies is unknown. However, examination of retrospective data provides anxiety about the leukaemogenic risk of the commonly used cytoreductive agent, hydroxyurea. From an analysis of a few relatively small studies of primary thrombocythaemia, the incidence of acute leukaemic transformation in selected patients treated with hydroxyurea has been given as 5-10% over 4-11 years (1).

Based on the risk factors for vascular occlusion, older patients with a thrombotic history and high platelet count can be separated into a 'high' risk group. There is evidence from a randomised prospective study of 'high-risk' patients that cytoreduction with hydroxyurea significantly reduces vascular occlusion (2). The observed reduction in this prospective study of 29 months median duration was from 24% for those not given cytoreductive treatment to 3.6% for those receiving hydroxyurea - approximately a six-fold reduction. In another prospective study where all patients received hydroxyurea, an incidence of major thrombotic events was 5.6%/year (3). In these high-risk patients, cytoreductive treatment should therefore be given. The high risk arm of the PT1 trial, which has now closed, assessed the cytoreductive treatment of choice for these high risk patients and the results suggest that hydroxyurea plus aspirin is superior to anagrelide plus aspirin (4).

In the patients at lower risk of vascular occlusion the dilemma is that the risk of vascular occlusion in untreated patients is relatively low, but includes major life-threatening events. In two small prospective studies of these patients not receiving platelet lowering agents, the observed major complications were 3% and 4.1% per year and the total complications were 5.1% and 10.5% per year respectively (1). Cyto-reductive treatment should prevent such events and one could predict a similar reduction in complications as seen in the high-risk patients. However, there is evidence that in patients under the age of 40 years the complication rate is only one quarter of that seen in patients aged 40 - 59 years (5). Therefore it has been decided to divide these patients at lower risk of vascular occlusion into 'intermediate' and 'low risk' groups. Patients aged 40-59 years will fall into the 'intermediate risk' group and will be randomised to cytoreduction or not, while all will receive aspirin. Patients under 40 years will form the 'low-risk' group and will receive aspirin alone. Cyto-reductive treatment might also delay myelofibrotic transformation as observed in primary polycythaemia. However, this benefit and the possible reduction in vaso-occlusive episodes need to be balanced against the potential long-term risk of increasing acute leukaemic transformation.