The anti-platelet drug aAnagrelide (Chinese alias: cloquimizolone, aAnagrelide hydrochloride) is highly selective, with few side effects, and is mainly used for the treatment of primary thrombocythemia and other myeloproliferative disorders caused by thrombocythemia. Mechanism of action Anagrelide mainly acts on megakaryocytes, inhibiting the activity of cyclic phosphatidyl adenosine (cAMP) phosphodiesterase, increasing the level of cAMP in platelets, thus inhibiting platelet aggregation and morphological changes, and inhibiting the maturation of megakaryocytes. The results of numerous studies have found that anagrelide affects the maturation of megakaryocytes both in vitro and in vivo, leading to smaller cell bodies and changes in morphological characteristics, and suggest that anagrelide reduces the number of platelets mainly because of intervention in the maturation of megakaryocytes. In vitro experiments have revealed that anagrelide can inhibit the development of megakaryocyte clones or disrupt and prevent the maturation of megakaryocytes by reducing the size and ploidy of megakaryocytes, and that these effects occur in the latter, non-dividing phase of megakaryocyte development. Kinetic characteristics Anagrelide is rapidly absorbed and widely distributed in the body. Most of it is metabolized in the liver and the metabolites are excreted mainly by the kidneys, with less than 1% excreted in the urine in its original form. A single oral dose of 1 mg of anagrelide reaches maximum plasma concentration after 0.9 hours, with an elimination half-life of about 7.6 hours. Clinical Evaluation A non-controlled study of 546 patients with primary thrombocytosis and platelet counts above 900 x 10^9/liter found that after a mean of 65 weeks of treatment, more than 70% of patients had platelet counts down to 50% of pre-treatment or below 600 x 10^9/liter, and the effect lasted for 4 years. Twelve patients with chronic granulocytic leukemia were studied with anagrelide in combination with conventional therapy, all of whom were treated with hydroxyurea and some of whom were treated with alpha-interferon (alone or in combination with hydroxyurea), leucovorin or melphalan. Platelets before the use of anagrelide were (970-3600) × 10^9 liters (mean 2000 × 10^9/liter ), and seven patients had bleeding and coagulation complications. The platelet count decreased to less than 600×10^9/liter (median 343×10^9/liter ) in all patients after treatment, and the bleeding and coagulation symptoms disappeared. The median dose of anagrelide was 1.9 mg daily. The results showed that the antiplatelet effect of anagrelide was significant. In patients with chronic granulocytic leukemia, anagrelide is a useful adjunctive agent when thrombocytosis cannot be controlled by conventional therapy. Anagrelide was administered to 942 patients with thrombocytosis, including 113 patients with true erythrocytosis, at a mean dose of 2.4 mg daily, with an overall effectiveness of 74%, including 66% complete remission and 8% partial remission, with the time to complete remission ranging from 17 to 25 days. The clinical efficacy of anagrelide was observed in 48 patients with primary thrombocythemia, 41 of whom had a history of thrombosis or bleeding complications, 16 without any treatment, 15 with hydroxyurea, and the other 17 with multiple drugs. The platelet count of the patients before anagrelide treatment was (850-3100) × 10^9/liter , with complete remission 87%, partial remission or ineffective 13%, and about 10% of the patients discontinued treatment due to adverse effects, and most patients had been treated for 7 years (mean dose of 2.5 mg daily). The results suggest that anagrelide reduces the number of platelets while reducing the incidence of thrombotic complications. Drug safety About 25% to 37% of patients on anagrelide therapy had adverse reactions of varying degrees, mainly including headache, hypotension, diarrhea, fluid retention, palpitations, arrhythmia, cough, nausea and vomiting. However, the reactions are mild, mostly occurring in the early stages and resolving on their own. About 10% of patients stop treatment due to serious adverse reactions. Slight transient anemia has been reported with long-term treatment, and severe allergic pneumonia and congestive heart failure have been reported occasionally. The dose required to produce anticoagulation with anagrelide is approximately 10 times higher than the dose used with antiplatelets; therefore, the routinely used antiplatelet dose has no effect on platelet coagulation.