PMID- 35021888
OWN - NLM
STAT- MEDLINE
DCOM- 20220606
LR  - 20230906
IS  - 2159-3345 (Electronic)
IS  - 2159-3337 (Print)
IS  - 2159-3337 (Linking)
VI  - 32
IP  - 3
DP  - 2022 Jun
TI  - Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in 
      Cardiopulmonary Bypass and COVID-19.
PG  - 139-150
LID - 10.1089/nat.2021.0077 [doi]
AB  - 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.
FAU - Chabata, Charlene V
AU  - Chabata CV
AUID- ORCID: 0000-0001-5626-6906
AD  - Department of Surgery, Department of Medicine, Duke University Medical Centre, 
      Durham, North Carolina, USA.
AD  - Department of Pharmacology and Cancer Biology, Duke University, Durham, North 
      Carolina, USA.
FAU - Frederiksen, James W
AU  - Frederiksen JW
AD  - Department of Surgery, Department of Medicine, Duke University Medical Centre, 
      Durham, North Carolina, USA.
FAU - Olson, Lyra B
AU  - Olson LB
AD  - Department of Surgery, Department of Medicine, Duke University Medical Centre, 
      Durham, North Carolina, USA.
AD  - Department of Pharmacology and Cancer Biology, Duke University, Durham, North 
      Carolina, USA.
AD  - Medical Scientist Training Program, Duke University, Durham, North Carolina, USA.
FAU - Naqvi, Ibtehaj A
AU  - Naqvi IA
AD  - Department of Surgery, Department of Medicine, Duke University Medical Centre, 
      Durham, North Carolina, USA.
AD  - Department of Anesthesiology, Department of Medicine, Duke University Medical 
      Centre, Durham, North Carolina, USA.
FAU - Hall, Sharon E
AU  - Hall SE
AD  - Division of Hematology, Department of Medicine, Duke University Medical Centre, 
      Durham, North Carolina, USA.
FAU - Gunaratne, Ruwan
AU  - Gunaratne R
AD  - Department of Medicine, Stanford University Medical Center, Stanford, California, 
      USA.
FAU - Kraft, Bryan D
AU  - Kraft BD
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 
      Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
FAU - Que, Loretta G
AU  - Que LG
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 
      Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
FAU - Chen, Lingye
AU  - Chen L
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 
      Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
FAU - Sullenger, Bruce A
AU  - Sullenger BA
AD  - Department of Surgery, Department of Medicine, Duke University Medical Centre, 
      Durham, North Carolina, USA.
AD  - Department of Pharmacology and Cancer Biology, Duke University, Durham, North 
      Carolina, USA.
LA  - eng
GR  - P01 HL074124/HL/NHLBI NIH HHS/United States
GR  - P01 HL139420/HL/NHLBI NIH HHS/United States
GR  - T32 GM007171/GM/NIGMS NIH HHS/United States
GR  - T32 GM145449/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220112
PL  - United States
TA  - Nucleic Acid Ther
JT  - Nucleic acid therapeutics
JID - 101562758
RN  - 0 (Anticoagulants)
RN  - 0 (Aptamers, Nucleotide)
RN  - 9001-29-0 (Factor X)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Anticoagulants/pharmacology/therapeutic use
MH  - *Aptamers, Nucleotide/genetics/pharmacology/therapeutic use
MH  - *COVID-19
MH  - Cardiopulmonary Bypass/adverse effects
MH  - Factor X
MH  - Heparin
MH  - Humans
MH  - Thrombin
PMC - PMC9221171
OTO - NOTNLM
OT  - COVID-19
OT  - anticoagulation
OT  - aptamer
OT  - cardiopulmonary bypass
OT  - heparin
OT  - thrombin generation
COIS- Duke has submitted patent applications on the factor X/Xa anticoagulant 
      aptamer(s) and combinations of the aptamer with other anticoagulants. Dr. 
      Sullenger and Dr. Frederiksen are inventors on such Duke Intellectual Property.
EDAT- 2022/01/14 06:00
MHDA- 2022/06/07 06:00
PMCR- 2023/06/01
CRDT- 2022/01/13 05:33
PHST- 2022/01/14 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/01/13 05:33 [entrez]
PHST- 2023/06/01 00:00 [pmc-release]
AID - 10.1089/nat.2021.0077 [pii]
AID - 10.1089/nat.2021.0077 [doi]
PST - ppublish
SO  - Nucleic Acid Ther. 2022 Jun;32(3):139-150. doi: 10.1089/nat.2021.0077. Epub 2022 
      Jan 12.