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Effects of Antithrombotic and Results of Drug Screening
Published in Josef Hladovec, 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).
Management of Myelofibrosis
Published in Richard T. Silver, Ayalew Tefferi, Myeloproliferative Disorders, 2007
Cervantes Francisco, Giovanni Barosi
Besides autoimmune hemolytic anemia, corticosteroids have been reported to improve nonhemolytic anemia in some patients with PMF (37). Cyclosporin A has been employed in patients with severe anemia and autoimmune features, including positive Coombs’ test, antinuclear and antimitochondrial antibodies, and circulating immune complexes, who are refractory to prednisone. In a series of 10 such patients, 3 of the 6 who could complete 6 months of treatment responded favorably, with a high CD4/CD8 ratio being the best predictor of the response (38). Finally, anagrelide can be useful to treat the thrombocytosis that is uncontrollable by hydroxyurea (39).
Developments in diagnosis and treatment of essential thrombocythemia
Published in Expert Review of Hematology, 2019
Barbara Mora, Francesco Passamonti
Therapies must be chosen on the basis of prognostication. LD-ASA indications in ET are neither definitive nor clearly evidence-based, although the vast majority of physicians treating ET translate data obtained in PV. A personalized approach on the basis of the mutation profile is of interest: in CALR-mutated LR patients probably aspirin is not necessary. Hydroxyurea is the first line treatment. Its activity and safety are well recognized. Some Authors are worried about leukemogenicity of hydroxyurea. However, we have to consider that cytogenetic profile, driver mutations and non-driver mutations have been demonstrated to impact on leukemic transformation at the time of ET diagnosis. This limits the effect of HU per se. Interferon is effective and indicated in younger patients. Anagrelide is for second-line treatment according to MPN experts; however, it can be used also for the first line.
Emerging therapies for the treatment of essential thrombocythemia
Published in Expert Opinion on Orphan Drugs, 2018
Adolfo Enrique Diaz, Robin M. Scherber, Ruben A. Mesa
In view of the near-to-normal life expectancy of this condition, the main focus of the management has been put on prevention of thrombotic and hemorrhagic events. Strong prognostic tools such as the IPSET-thrombosis are commonly used to risk stratify each patient with diagnosis of ET and then treat accordingly. Initial pharmacotherapy options include aspirin, hydroxyurea, and anagrelide, which for the most part are efficacious and have an acceptable toxicity profile; thus far, those remain suboptimal only to the minority of patients and intolerable to a small fraction of them. In typical hematology practice, INF is less frequently used despite its clinical efficacy in view of voiced concerns of tolerability. However, newer preparations such as pegylated-IFN that has a more favorable toxicity profile is the focus of ongoing clinical trials in an effort to better define its future role. Other exciting agents in clinical trials including JAK inhibitors, Histone Deacetylase (HDAC) Inhibitors, Telomerase Inhibitors, and Human Double Minute 2 (HDM2) inhibitors would be reserved for the small fraction of patients who do not respond or cannot tolerate standard therapies, and their future development would reside in their toxicity profile, since current treatments are associated with little-to-no toxicity. Our role as investigators will remain to be participants and judges of data coming from rigorously constructed and performed phase 3 studies able to compel evidence of superiority of one agent over the other.
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.