Genic) has 3-MA site prompted the consideration of two main alternative drugs: anagrelide
Genic) has prompted the consideration of two main alternative drugs: anagrelide, now authorized for marketing in European countries, and interferon (IFN-). Two more medications, pipobroman (available only in certain European countries) and busulfan are also used as platelet-lowering drugs in ET patients, as well as platelet apheresis, which may be the preferred therapeutic option in case of emergency. Hydroxyurea (Hydroxycarbamide, HU) Efficacy The efficiency of HU in controlling the PubMed ID: platelet number in high risk ET patients has been further documented by the recently published results of the MRC PT1 trial [63]. A lack of platelet control was observed in less than 4 (15 patients) of the 404 patients treated by HU. At 3 months 90 of the patients had a platelet number <600 ?109/L. The median platelet count at 6 months was <400 ?109/L. Stable reduction of the median platelet number (lower or equal to 400 ?109/L) was obtained with HU for the following 24 months. Importantly, the protection from thrombosis in high risk ET patients already demonstrated by Cortellazzo et al. with HU (plus anti-aggregating agents in almost 70 of the patients) [62] was confirmed by this study with HU associated with Asp in all the patients. After 2 years, the prevalence of thrombotic events was 4 , identical to the former study of Cortelazzo, and significantly lower than the prevalence of 24 found in the control group [62]. Side effects Clinical and hematological tolerance of HU is usually good even during very long periods of time. Major shortThe role of Asp in the prevention of arterial thromboses has been clearly established in the general population. The benefit of a low dose Asp in preventing the risk of thrombotic complications without increasing significantly the hemorrhagic risk in PV patients has recently been demonstrated in the extensive prospective ECLAP study [57]. A preliminary pilot study in polycythemia patients receiving either 40 mg/day of Asp or a placebo showed that this dosage fully inhibited the cyclooxygenase activity and did not cause any major hemorrhage [58]. Anti-platelet therapy has not yet prospectively been shown to reduce the incidence of thrombosis in ET, however, the combination of an anti-aggregating agent with cytoreductive therapy has been found to be safe and to reduce the incidence of thrombosis in ET patients in retrospective studies [59,60]. Low dose Asp is often prescribed as soon as an excess of platelets is discovered by the gen-Page 7 of(page number not for citation purposes)Orphanet Journal of Rare Diseases 2007, 2: toxic effects are dose limiting hematological impairment and fever. However, oral and leg ulcers and other skin lesions are currently observed but often only after several months or years of treatment, suggesting the role in their occurrence of the cumulative dose received.Mutagenic potential and long term resistance HU was initially introduced in the treatment of ET patients because it is supposedly non mutagenic. Its mechanism of action is the inhibition of DNA synthesis by blocking the ribonucleoside reductase activity. As leukemogenic effects of HU have not been definitively eliminated, this molecule should be used cautiously in young individuals. After a continuous use in ET patients, the non selective effect of the drug on platelet reduction may, in the long run decrease, lead to anemia and neutropenia after dosage escalation of HU. This delayed hematological t.

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