Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19.

Journal Article (Journal Article)

Known limitations of unfractionated heparin (UFH) have encouraged the evaluation of anticoagulant aptamers as alternatives to UFH in highly procoagulant settings such as cardiopulmonary bypass (CPB). Despite progress, these efforts have not been totally successful. We take a different approach and explore whether properties of an anticoagulant aptamer can complement UFH, rather than replace it, to address shortcomings with UFH use. Combining RNA aptamer 11F7t, which targets factor X/Xa, with UFH (or low molecular weight heparin) yields a significantly enhanced anticoagulant cocktail effective in normal and COVID-19 patient blood. This aptamer-UFH combination (1) supports continuous circulation of human blood through an ex vivo membrane oxygenation circuit, as is required for patients undergoing CPB and COVID-19 patients requiring extracorporeal membrane oxygenation, (2) allows for a reduced level of UFH to be employed, (3) more effectively limits thrombin generation compared to UFH alone, and (4) is rapidly reversed by the administration of protamine sulfate, the standard treatment for reversing UFH clinically following CPB. Thus, the combination of factor X/Xa aptamer and UFH has significantly improved anticoagulant properties compared to UFH alone and underscores the potential of RNA aptamers to improve medical management of acute care patients requiring potent yet rapidly reversible anticoagulation.

Full Text

Duke Authors

Cited Authors

  • Chabata, CV; Frederiksen, JW; Olson, LB; Naqvi, IA; Hall, SE; Gunaratne, R; Kraft, BD; Que, LG; Chen, L; Sullenger, BA

Published Date

  • June 2022

Published In

Volume / Issue

  • 32 / 3

Start / End Page

  • 139 - 150

PubMed ID

  • 35021888

Pubmed Central ID

  • PMC9221171

Electronic International Standard Serial Number (EISSN)

  • 2159-3345

Digital Object Identifier (DOI)

  • 10.1089/nat.2021.0077


  • eng

Conference Location

  • United States