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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nimjee, SM; Lohrmann, JD; Wang, H; Snyder, DJ; Cummings, TJ; Becker, RC; Oney, S; Sullenger, BA

Published Date

  • February 2012

Published In

Volume / Issue

  • 20 / 2

Start / End Page

  • 391 - 397

PubMed ID

  • 22086230

Pubmed Central ID

  • 22086230

Electronic International Standard Serial Number (EISSN)

  • 1525-0024

Digital Object Identifier (DOI)

  • 10.1038/mt.2011.226

Language

  • eng

Conference Location

  • United States