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

Publication ,  Journal Article
Chabata, CV; Frederiksen, JW; Olson, LB; Naqvi, IA; Hall, SE; Gunaratne, R; Kraft, BD; Que, LG; Chen, L; Sullenger, BA
Published in: Nucleic Acid Ther
June 2022

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.

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Published In

Nucleic Acid Ther

DOI

EISSN

2159-3345

Publication Date

June 2022

Volume

32

Issue

3

Start / End Page

139 / 150

Location

United States

Related Subject Headings

  • Thrombin
  • Humans
  • Heparin
  • Factor X
  • Cardiopulmonary Bypass
  • COVID-19
  • Aptamers, Nucleotide
  • Anticoagulants
 

Citation

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Chabata, C. V., Frederiksen, J. W., Olson, L. B., Naqvi, I. A., Hall, S. E., Gunaratne, R., … Sullenger, B. A. (2022). Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19. Nucleic Acid Ther, 32(3), 139–150. https://doi.org/10.1089/nat.2021.0077
Chabata, Charlene V., James W. Frederiksen, Lyra B. Olson, Ibtehaj A. Naqvi, Sharon E. Hall, Ruwan Gunaratne, Bryan D. Kraft, Loretta G. Que, Lingye Chen, and Bruce A. Sullenger. “Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19.Nucleic Acid Ther 32, no. 3 (June 2022): 139–50. https://doi.org/10.1089/nat.2021.0077.
Chabata CV, Frederiksen JW, Olson LB, Naqvi IA, Hall SE, Gunaratne R, et al. Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19. Nucleic Acid Ther. 2022 Jun;32(3):139–50.
Chabata, Charlene V., et al. “Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19.Nucleic Acid Ther, vol. 32, no. 3, June 2022, pp. 139–50. Pubmed, doi:10.1089/nat.2021.0077.
Chabata CV, Frederiksen JW, Olson LB, Naqvi IA, Hall SE, Gunaratne R, Kraft BD, Que LG, Chen L, Sullenger BA. Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19. Nucleic Acid Ther. 2022 Jun;32(3):139–150.
Journal cover image

Published In

Nucleic Acid Ther

DOI

EISSN

2159-3345

Publication Date

June 2022

Volume

32

Issue

3

Start / End Page

139 / 150

Location

United States

Related Subject Headings

  • Thrombin
  • Humans
  • Heparin
  • Factor X
  • Cardiopulmonary Bypass
  • COVID-19
  • Aptamers, Nucleotide
  • Anticoagulants