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Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor.

Publication ,  Journal Article
Nimjee, SM; Lohrmann, JD; Wang, H; Snyder, DJ; Cummings, TJ; Becker, RC; Oney, S; Sullenger, BA
Published in: Mol Ther
February 2012

Millions of individuals are prescribed platelet inhibitors, such as aspirin and clopidogrel, to reduce their risk of thrombosis-related clinical events. Unfortunately many platelet inhibitors are contraindicated in surgical settings because of their inherent bleeding risk complicating the treatment of patients who require surgery. We describe the development of a potent antiplatelet agent, an RNA aptamer-termed Ch-9.14-T10 that binds von Willebrand factor (VWF) with high affinity and inhibits thrombosis in a murine carotid artery damage model. As expected, when this potent antiplatelet agent is administered, it greatly increases bleeding from animals that are surgically challenged. To improve this antiplatelet agent's safety profile, we describe the generation of antidotes that can rapidly reverse the activity of Ch-9.14-T10 and limit blood loss from surgically challenged animals. Our work represents the first antidote controllable antiplatelet agent, which could conceivably lead to improved medical management of patients requiring antiplatelet medication who also need surgery.

Duke Scholars

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Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

February 2012

Volume

20

Issue

2

Start / End Page

391 / 397

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • Thrombosis
  • Platelet Aggregation Inhibitors
  • Platelet Activation
  • Oligonucleotides
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice
  • Hemorrhage
  • Cyclodextrins
 

Citation

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Nimjee, S. M., Lohrmann, J. D., Wang, H., Snyder, D. J., Cummings, T. J., Becker, R. C., … Sullenger, B. A. (2012). Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor. Mol Ther, 20(2), 391–397. https://doi.org/10.1038/mt.2011.226
Nimjee, Shahid M., Jens D. Lohrmann, Haichen Wang, David J. Snyder, Thomas J. Cummings, Richard C. Becker, Sabah Oney, and Bruce A. Sullenger. “Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor.Mol Ther 20, no. 2 (February 2012): 391–97. https://doi.org/10.1038/mt.2011.226.
Nimjee SM, Lohrmann JD, Wang H, Snyder DJ, Cummings TJ, Becker RC, et al. Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor. Mol Ther. 2012 Feb;20(2):391–7.
Nimjee, Shahid M., et al. “Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor.Mol Ther, vol. 20, no. 2, Feb. 2012, pp. 391–97. Pubmed, doi:10.1038/mt.2011.226.
Nimjee SM, Lohrmann JD, Wang H, Snyder DJ, Cummings TJ, Becker RC, Oney S, Sullenger BA. Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor. Mol Ther. 2012 Feb;20(2):391–397.

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

February 2012

Volume

20

Issue

2

Start / End Page

391 / 397

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • Thrombosis
  • Platelet Aggregation Inhibitors
  • Platelet Activation
  • Oligonucleotides
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice
  • Hemorrhage
  • Cyclodextrins