Hydroxyurea hydroxycarbamide in sickle cell anaemia

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section is required to maintain a normal haematocrit or if the platelet count continues high (added risk of thrombosis).

Radiophosphorus (32P, sodium radiophosphate) is given i.v. Phosphorus is concentrated in bone and in cells that are dividing rapidly, so that the erythrocyte precursors in the bone marrow receive most of the P-irradiation. The effects are similar to those of whole-body irradiation, and in PRV, 32P is a treatment option for those > 65 years (accumulation in the gonads precludes its use in younger patients). The maximum effect on the blood count is delayed 1-2 months after a single dose that usually provides control for 1-2 years. It reduces vascular events and delays progression to myelofibrosis. Excessive depression of the bone marrow including leucocytes and platelets is the main adverse effect, but is seldom serious. Acute myeloid leukaemia occurs more frequently in patients treated with 32P especially when used in combination with hydroxyurea.

Alkylating agents. Busulfan is a radio-mimetic cytotoxic agent that is effective in PRV, reducing vascular events and delaying myelofibrosis. Its mutagenic potential should restrict its use to older patients. Chlorambucil and combination chemotherapy should be avoided because of excessive leukaemogenic risk.

Hydroxyurea (hydroxycarbamide). This antimetabolite is thought to carry a lower risk of leukaemogenesis than either of the above agents but anxieties remain. It effectively reduces the incidence of thrombosis and is regarded as more acceptable therapy for younger patients.

Anagrelide is an oral agent which inhibits platelet aggregation but at lower doses it lowers platelet counts in man due to a marked effect on megakaryocyte maturation. It is nonmutagenic and effectively controls thrombocytosis in PRV and essential thrombocythaemia (ET). Adverse effects are cardiovascular: headache, forceful heartbeats, fluid retention and arrhythmias.

Interferon alfa is another probably non-leuk-aemogenic alternative for younger patients.

Other features. Pruritus is troublesome and difficult to relieve; it may be helped by 11,- and

H2-histamine receptor blockers alone or together. Hyperuricaemia, due to cell destruction, is prevented by allopurinol; and iron and folate deficiency by replacement doses (due to the rapid response of the myeloproliferative erythron). Aspirin remains controversial. Low-dose aspirin (for antiplatelet action) may be used if the platelet count remains high or thrombosis occurs despite the above treatment but is best avoided in patients with a history of haemorrhage.

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