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Paper of the Month: Seeking a balance between blood clotting and uncontrolled bleeding

07/23/10  Portland, Ore.

Science Translational MedicineThis month's featured paper was published in the June 23 edition of the journal Science Translational Medicine, and is titled “Safety and antithrombotic efficacy of moderate platelet count reduction by thrombopoietin inhibition in primates.”

The research was conducted by an investigative team in the Department of Biomedical Engineering led by Stephen R. Hanson, PhD, Professor. The full author list is provided at the end of this summary.

Blood platelets – cells that circulate in the blood and can become sticky – play a role in the formation of blood clots (thrombosis). Certain drugs, such as low dose aspirin and Plavix, block the ability of platelets to form blood clots. But they also block the beneficial role of platelets in helping to stop bleeding and can lead to serious, even fatal, bleeding. The editors of the journal likened the research purpose Steve Hansonto “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.” As reported in the paper, in non-human primates, even modest lowering of platelets within the normal range – achieved by inhibiting platelet production by the bone marrow – markedly reduced the formation of platelet clots (thrombosis) and prevented the blockage of blood flow (occlusive thrombosis) in models of injured blood vessels. Importantly, by keeping platelet numbers within the physiological normal range, no increased bleeding was seen.

The research relied on the development of a baboon anti-serum against the human hormone that is responsible for platelet production in the bone marrow (thrombopoietin). The anti-serum, also active against the analogous baboon hormone for platelet production, was given to other baboons to lower their circulating platelets. The formation of platelet clots was then measured in clinically relevant baboon models of blood clotting in injured blood vessels. Clotting and blockage of blood flow was markedly reduced when Erik Tuckerplatelets were reduced, while the bleeding risk was unchanged. Importantly, giving aspirin to baboons with lowered platelets further reduced platelet clot formation (thrombosis), but with only the mild, clinically acceptable bleeding tendency caused by aspirin alone.

“Our findings suggested that higher platelet numbers, even within the normal physiologic range, may be a risk factor for adverse clotting events. Accordingly, the pharmacological lowering of platelet numbers within the normal physiological range may represent a new and exciting strategy for preventing platelet-related cardiovascular diseases,” said Dr. Hanson.

 

Author listing: E. I. Tucker, U. M. Marzec, M. A. Berny, S. Hurst, S. Bunting, O. J. T. McCarty, A. Gruber, S. R. Hanson.


 

PICTURED: Stephen Hanson (top), Eric Tucker, lead paper author (bottom)

 

 

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ABOUT THE PAPER OF THE MONTH

The School of Medicine newsletter spotlights a recently published faculty research paper in each issue. The goals are to highlight the great research happening at OHSU and to share this information across departments, institutes and disciplines. A list of all papers compiled by the OHSU Library and published by OHSU faculty during the prior month is also provided here. The monthly paper summary is selected by Associate Dean for Basic Science Mary Stenzel-Poore, PhD, and reviewed by Dean Mark Richardson, MD, MBA, and Vice President/Senior Associate Dean for Research Dan Dorsa, PhD.