The role of anagrelide in the treatment of essential thrombocytaemia

Abstract

BACKGROUND Essential thrombocytaemia is a myeloproliferative disease, characterized by an increased number of platelets in the peripheral blood, due to an increased production of such particles by the bone marrow. The primary event is the abnormal proliferation of megacariocytes. The objectives of treatment are the reduction of thrombohaemorragic events that occur in the course of the disease in high risk patients, because life expectancy is not affected. Nowadays hydroxyurea is the drug of choice to this purpose, but its use was related to a leukemogenic effect, although clinical data are still controversial. MECHANISMS OF ACTION Anagrelide is an oral agent that is able to significatively reduce the platelets count in these patients without effects on cell replication and nucleic acid synthesis. The mechanisms of action of this drug affect maturation, differentiation and growth of megacariocytes, by reducing intracellular cyclic AMP. Because the drug acts by inhibiting the phosphodiesterase enzyme, there are some important cardiovascular side effects, like vasodilatation, tachycardia, increase in cardiac output and hypotension. THERAPEUTIC EFFICACY AND STRATEGY Like hydroxyurea, anagrelide reduces the occurrence of thrombohaemorragic events in these patients, but venous thrombosis is more reduced than arterial, expecially when compared with hydroxyurea. To date, the role of anagrelide in the treatment of essential thrombocytaemia is the therapy of patients intolerant or refractory to the hydroxyurea: in perspective, its use could be proposed in younger patients (expecially women with child bearing potential) for long term treatment, or as second choice (after interferon) in pregnant women.