Management

• Aim to 5 risks and incidence of haemorrhagic and thrombotic complications by normalisation of platelet count (target <400 x 109/L); need to balance these risks with potential short and long term risks of therapy (e.g. aspirin) and cytotoxic therapy.

• Patients should be advised to make lifestyle changes (smoking, exercise, obesity) to reduce their risk of thrombosis and atherosclerosis.

252 • NSAIDs and standard dose aspirin should be avoided.

Low risk patients

• Incidence of thrombosis <2/100 patient years and haemorrhage

—1/100 patient years only; no added risk with pregnancy or surgery.

• Observation ± aspirin 75mg/d (if no contraindication) without cyto-toxic therapy.

Intermediate risk patients

• Cytoreductive therapy (see below) for patients with marked thrombocytosis (>1500 x 109/L) who are at increased risk of thrombosis.

• Others in this group may be treated with low dose aspirin (if no contraindication) and observation.

• Smokers should be encouraged to stop smoking and obese patients to lose weight to reduce their risks of thrombosis.

High risk patients

• Control of thrombocytosis with hydroxyurea reduces the risk of thrombosis in these patients (<4% vs. 24% after 2 years in a randomised study).

• Hydroxyurea: treatment of choice for patients >60 years (0.5-1.5g/d maintenance after higher initial doses to bring platelets <400 x 109/L); used in symptomatic patients <60 intolerant of anagrelide and inter-feron-a; some patients may need combination therapy with anagrelide or interferon-a to achieve normalisation of the platelet count; side effects myelosuppression, oral ulceration, rash; contraindicated in pregnancy and breast feeding.

• Anagrelide (2-2.5mg/d) is preferred in younger patients <60 years (especially those of childbearing potential); interferes with megakary-ocyte differentiation; side effects: headache, palpitations, fluid retention; contraindicated in pregnancy and patients with CCF or known cardiac disease.

• Interferon-a (3-5mU 3-5 x weekly) can control thrombocytosis due to ET in younger patients intolerant of anagrelide; not associated with risk of AML; rarely used due to inconvenience of administration and poor tolerance.

• 32P therapy (2.3mCi/m2 IV which may be repeated after 3-6 months) may be more appropriate in elderly patients (>75) or those unable to comply with regular hydroxyurea therapy; side effects: myelosuppression, long term risk of AML.

• Aspirin 75mg/d recommended for patients with thrombotic event; increases risk of haemorrhage (safest when platelets <1000 x 109/L); relieves erythromelalgia quickly (2-4 days); extreme caution in patients with haemorrhagic complications or history of peptic ulceration; H2-antagonist or proton pump inhibitors may be needed; markedly increased bleeding risk with higher aspirin doses. Dipyridamole is an alternative agent for those unable to tolerate aspirin.

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