Safety and antithrombotic efficacy of moderate platelet count reduction by thrombopoietin inhibition in primates

Sci Transl Med. 2010 Jun 23;2(37):37ra45. doi: 10.1126/scitranslmed.3000697.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antithrombins / adverse effects*
  • Antithrombins / pharmacology*
  • Bleeding Time
  • Blood Vessel Prosthesis
  • Heart Arrest / etiology
  • Heart Arrest / prevention & control
  • Humans
  • Male
  • Papio
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Count
  • Stroke / etiology
  • Stroke / prevention & control
  • Thrombopoietin / antagonists & inhibitors*
  • Thrombosis / blood
  • Thrombosis / complications
  • Thrombosis / pathology
  • Thrombosis / prevention & control*
  • Treatment Outcome


  • Antithrombins
  • Platelet Aggregation Inhibitors
  • Thrombopoietin