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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Another Way to Keep Blood Flowing Freely

Blood clotting is like walking a tightrope. If clots form too easily, they can lodge in blood vessels, depriving tissue of oxygen and instigating a stroke or heart attack. The danger on the other side is that blood fails to clot and small traumas can then cause uncontrolled bleeding. For most people, regulation of blood coagulation stays upright on the tightrope and blood flows freely inside vessels but clots readily when needed. But patients with cardiovascular disease need to avoid clotting. To keep blood flowing, some patients take antiplatelet medications such as aspirin or anticoagulants like Coumadin, but these drugs can tip the clotting balance too far and result in bleeding. The results from Tucker et al. suggest another approach to avoid unwanted blood clots. By inhibiting platelet formation at the source—in bone marrow—they lower the number of circulating platelets in baboons to a value that reduces clotting but is still within the acceptable range. Other platelet functions, including bleeding, remain normal.

The hormone thrombopoietin regulates the production of platelets in bone marrow by encouraging the differentiation of megakaryocytes, each of which fragments into large numbers of platelets. The authors injected baboons with an antibody to thrombopoietin to interfere with this process and so altered the number of platelets in the circulation to a value that was lower but still within the normal range. Subsequent testing showed that below a certain concentration, platelet reduction reduced thrombus formation, as shown by platelet deposition on collagen-coated grafts and by measuring the blockage of small-diameter grafts. Determining the time needed for a wound to stop bleeding showed that the platelet-lowering treatment did not change bleeding time.

Baboons are similar to humans when it comes to bleeding and clotting, so these results point to an interesting possibility. Although we already have drugs that inhibit blood clotting to give when patients need them, each drug has its drawbacks. This new possibility—manipulating platelet concentrations directly—provides a new tool that we may be able to use to keep people stable on the tightrope between clotting and bleeding.

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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