Research ArticleTHROMBUS Formation

Safety and Antithrombotic Efficacy of Moderate Platelet Count Reduction by Thrombopoietin Inhibition in Primates

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Science Translational Medicine  23 Jun 2010:
Vol. 2, Issue 37, pp. 37ra45
DOI: 10.1126/scitranslmed.3000697

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Abstract

Most heart attacks and strokes are caused by blood clots (thrombi) that block the vasculature. Because disease-causing arterial thrombosis depends on blood platelets, platelet inhibitors such as aspirin and clopidogrel effectively decrease the risk of thrombosis; however, they also impair platelet-dependent hemostasis that staunches bleeding from wounds and can therefore produce excessive bleeding. Experimental studies show that a reduction in the number of platelets also inhibits thrombosis, but these treatments also interfere with platelet function. Because normal hemostasis requires that the platelet concentration remain within a physiological range in the circulation, we evaluated whether lowering the number of circulating platelets—but only to a value still within the normal range—by inhibiting platelet formation in the bone marrow inhibits acute thrombogenesis in baboons. We reduced the platelet count with an inhibitor against the megakaryocyte-promoting hormone thrombopoietin and then showed that experimental occlusive thrombogenesis on collagen-coated vascular grafts was reduced, without impairment of primary hemostasis. These results suggest that suppressing platelet production without interfering with the hemostatic function of platelets may offer a safe alternative to current therapies for prevention of stroke and heart attack triggered by blood clotting.

Footnotes

  • Citation: E. I. Tucker, U. M. Marzec, M. A. Berny, S. Hurst, S. Bunting, O. J. T. McCarty, A. Gruber, S. R. Hanson, Safety and antithrombotic efficacy of moderate platelet count reduction by thrombopoietin inhibition in primates. Sci. Transl. Med. 2, 37ra45 (2010).

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