This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Extended release anagrelide will be developed for reducing platelet count (PLC) within the normal range. Patients with supranormal platelet count (PLC) have significantly increased risk of thrombosis. The extended-release dosage form of anagrelide, which is expected to be substantially safer than immediate-release anagrelide, is intended for the chronic treatment and prevention of arteriosclerotic/thrombotic events. Anagrelide, an FDA-approved compound, reduces PLC in a dose-dependent manner and has been used to treat this condition. PLC in the high-normal range (300/ni) is also associated with increased thrombotic risks. We have shown that platelet count in the normal range correlates with the progression of arterial-type experimental thrombosis in primates. Experimental and severe PLC reduction to the subnormal range (100/nl) is antithrombotic in several lower animal species. However, it has not yet been shown prospectively that decreasing PLC within the normal range (150/ni to 450/nl in baboons) has antithrombotic effect. Since anagrelide does not reduce PLC in species other than the human, we started to test alternative approaches to PLC reduction and its effect on thrombosis and hemostasis in primates.
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