Management of Polycythemia Vera
Richard T. Silver, Ayalew Tefferi in Myeloproliferative Disorders, 2007
Anagrelide is an imidazoquinazoline derivative; it inhibits cyclic nucleotide phosphodiesterase and the release of arachidonic acid from phospholipase. At concentrations higher than those used clinically, the drug inhibits platelet aggregation. At therapeutic concentrations, it displays a species-specific platelet-lowering effect in humans (86). In a study of 577 patients with MPD anagrelide therapy substantially reduced the platelet count in over 80% of the patients with PV (87). However, meaningful health outcome has not been evaluated in a controlled study. Furthermore, anagrelide is associated with some serious, albeit rare, side effects such as nonischemic cardiomyopathy (88,89). Additional limiting factors include the results of a recent randomized clinical trail in 809 patients with ET where the patients receiving anagrelide therapy experienced significantly higher rates of arterial thrombosis, serious hemorrhage, and fibrotic transformation (20). Since the platelet count in PV has not been shown to be an independent risk factor for thrombosis (45,46), the role of anagrelide in the treatment of PV remains uncertain. On a high risk patient with a significant increase in platelets in whom asprin is contraindicated, anagrelide may be considered.
Effects of Antithrombotic and Results of Drug Screening
Josef Hladovec in Antithrombotic Drugs in Thrombosis Models, 2020
Anagrelide is another theoretically interesting drug unrelated to other antiplatelet agents. It is chemically an imidazoquinazoline.76, 636, 637 While studying the experimental data about the antithrombotic activity of this drug, one has the impression that it was discovered in a screening for in vitro antiaggregatory activity. This is already suggested by the name chosen for the drug. Anagrelide was in vitro very effective against aggregation induced by all agents. Particularly primary aggregation, and at a still lower concentration, the shape change was influenced. It turned out to be more potent than any other synthetic antithrombotic drug. A corresponding effectiveness was observed in several species even ex vivo after oral administration.76, 638 While in vitro the aggregation of human platelets was inhibited less than of platelets of other species, ex vivo the drug was more effective in man than in other species (0.25 to 5 mg/kg in animals and about 0.07 mg/kg p.o. in man).
Contemporary management of essential thrombocythemia in children
Published in Expert Review of Hematology, 2019
Maria Luigia Randi, Irene Bertozzi, Maria Caterina Putti
Anagrelide is an orally active, quinazolone-derived, platelet-lowering agent that acts by blocking megakaryocyte maturation and polyploidization as well as proplatelet formation [56]. Anagrelide is licensed in Europe for patients with ET intolerant/refractory to HU and in some countries it is authorized as first-line therapy [57]. ELN [54] recommends anagrelide (0.5–2.5 mg/day) as second line therapy in ET. It is tolerable in the long-term; however, anemia occurs in about 1/4 of treated cases after a couple of years of treatment. Some studies [58] carried out before the description of CALR mutations and pre-fibrotic myelofibrosis (PMF) histologic recognition, described an increase in marrow fibrosis with anagrelide, even if not in pediatric cases.
A spotlight on the management of complications associated with myeloproliferative neoplasms: a clinician’s perspective
Published in Expert Review of Hematology, 2018
Graeme Greenfield, Mary F. McMullin
In ET the role of HU was examined in the PT-1, ANAHYDRET and EXELS studies. ANAHYDRET demonstrated noninferiority of anagrelide in comparison to HU [70]. The other two studies demonstrated a reduction in arterial thrombosis rate but an increase in venous thrombosis in patients treated with HU in comparison to patients treated with anagrelide [34,71]. Anagrelide works specifically to reduce platelet counts by inhibiting megakaryocyte maturation. It has an equivalent effect to HU in reduction of the platelet count and is recommended as an option in ET where patients have failed on or been intolerant of HU [41,42,67].
Anagrelide is an anti-megakaryocytic and not an anti-platelet agent
Published in Platelets, 2019
Anagrelide is orally active and has been used in the clinic for over 20 years for treatment of myeloproliferative disorders, such as essential thrombocythaemia which is associated with an over-production of platelets and increased risk of thrombosis [7]. Anagrelide remains the only clinically available small molecule that lowers platelets counts without an effect on red or white cell production, and is therefore a unique agent [8]. Anagrelide is well tolerated and does not prolong bleeding or increase bruising, consistent with only a fraction of circulating platelets being required for normal haemostasis [5,9].
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