Anagrelide: 20 years later.
Thrombocytosis is a common feature of chronic myeloproliferative disorders (MPD) and may be asymptomatic or associated with transient microvascular vaso-occlusive symptoms or large vessel arterial or venous thrombosis. Failure of either the hematocrit or the platelet count to correlate with thrombotic events is a peculiar conundrum of the MPDs. Asymptomatic thrombocytosis in young MPD patients with no cardiovascular risk factors does not require treatment. It is also undisputed that lowering the platelet count reduces the incidence of microvascular events in MPD patients. At the same time, no study to date has demonstrated that platelet count reduction prolongs survival in MPD patients. Agents such as hydroxyurea, busulfan, IFN-alpha and anagrelide, have been used to reduce an elevated platelet count and decrease thrombohemorrhagic events in at-risk patients with thrombocytosis associated with an MPD. When treatment is required, it makes sense to use drugs that are not myelotoxic or mutagenic. Based on the Primary Thrombocythaemia 1 study, hydroxyurea is the treatment of choice for thrombocytosis-associated transient ischemic attacks. However, hydroxyurea does not prevent venous thrombosis, is not more effective in preventing arterial thrombosis than anagrelide and its long-term safety is not established. Therefore, unless curative therapy is planned, one should use the least myelotoxic agent when platelet count reduction is required. In this regard, anagrelide can be considered a first-line drug. With regard to long-term safety of anagrelide, the EMEA has required close monitoring of the safety points identified in future Periodic Safety Update Reports and in a Post Authorisation Safety Study in the EU, which will focus especially on cardiovascular events and acute leukemia. In this article, we review anagrelide pharmacology, the physiology of thrombopoiesis, the differential diagnosis of thrombocytosis and the management of patients with an elevated platelet count.
Emadi
Ashkan
A
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA.
Spivak
Jerry L
JL
D006801:Humans; D009196:Myeloproliferative Disorders / Q000150:complications / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013922:Thrombocytosis / Q000150:complications / Q000188:drug therapy*
D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C021139:anagrelide