In younger patients (<40) who have a low risk of cerebrovascular or cardiovascular events the use of venesection in combination with low dose aspirin and non-leukaemogenic therapy such as anagrelide or IFN-a should be considered to reduce the risk of leukaemia.
Venesection: to 5 blood volume to normal as rapidly as possible and prevent complications (target Hct <0.45). Removal of RBCs by venesection is the quickest way of reducing red cell mass. 450mL blood (± isovolaemic replacement with 0.9% saline) removed safely from younger adults every 2-3 days (5 volume or frequency to twice weekly in older patients). If Hct very high (>0.60) venesection may be technically difficult due to extreme viscosity.
Maintenance therapy: venesection alone can be used to maintain the Hct at 0.42-0.45. Individual requirements are variable (e.g. 2 procedures per year to monthly venesection). However, early studies showed 4 risk of thrombosis in first 3 years after treatment with venesection alone thus additional myelosuppressive treatment is required in most patients.
Hydroxyurea: an antimetabolite (ribonucleotide reductase inhibitor), is most commonly used therapy. Onset of myelosuppression with hydroxyurea is rapid, but overdosage quickly corrected by temporary withdrawal. Once Hct 5, a daily dosage of 10-20mg/kg/d normally sufficient as maintenance therapy. Lower incidence of thrombosis by ensuring better Hct (<0.45) and platelet counts (<400 x 109/L). Lower incidence of leukaemia than 32P/alkylator therapy but still concerns.
Radioactive phosphorus (32P) and busulfan: long established treatments for PV. Produce 5 in RCM 6-12 weeks after administration (32P 2.3 mCi/m2 by IV injection every 12 weeks as necessary; busulfan by single oral dose 0.5-1mg/kg). Either agent may be repeated after 3-6 months if further myelosuppression is required. Both individually 5 thrombosis and myelofibrosis but markedly 4 the risk of AML. The use of 32P and either busulfan or hydroxyurea in an individual is associated with a very high risk of AML. Neither is recommended for patients <65 years who should receive hydroxyurea. However, in patients >65 in whom compliance or regular monitoring of hydroxyurea dose may be a problem busulfan or 32P can be considered as both offer intermittent therapy rather than long term maintenance.
Anagrelide: oral imidazoquinazoline with anti-cyclic AMP phosphodiesterase activity and profound effect on megakaryocyte maturation resulting in reduced platelet production. No evidence of mutagenic activity. Useful for control of thrombocytosis in PV but no effect on splenomegaly or other lineages. Side effects: headache (50%), forceful heartbeat, fluid retention, dizziness, arrhythmia (<10%) and CCF (2%). Use with caution in patients with known or suspected cardiac disease.
Aspirin: 75mg daily as antiplatelet therapy is common practice in myeloproliferative conditions. Higher doses are associated with haemorrhage. Large trial of low dose aspirin (40mg/d) in progress. Meantime reasonable to use 40mg/d aspirin in patients with history of MI 244 or thrombotic CVA, erythromelalgia and other microvascular neurological and ocular disturbances. Avoid in those with a history of haemorrhage particularly in the GI tract.
Interferon-a therapy at a dose of 3-5MU three times weekly can control erythrocytosis and 5 leucocytosis, thrombocytosis and splenomegaly in 60-75% of patients over 6-12 months. A useful observation is that it can diminish the severity of pruritus in 80% of patients. Tolerance is a problem but may be reduced by the use of pegylated-interferon.
Supportive treatment: maintain adequate fluid intake and avoid dehydration. Give allopurinol to minimise complications of hyperuricaemia. Acute gout is managed by standard therapies. Pruritus is a troublesome complication for some patients, unfortunately there is no satisfactory treatment. Sometimes abates when excess myeloproliferation controlled and Hct reduced but may persist despite adequate control of the Hct. Worth trying antihistamines, ^-antagonists or interferon-a.
Surgical procedures relatively contraindicated in active PV: defer until Hct and platelets normalised for >2 months due to risk of thrombotic and haemorrhagic complications; if emergency surgery necessary perform venesection and cytapheresis.
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