Targeting the contact system in a rabbit model of extracorporeal membrane oxygenation Article Swipe
James S. Tweddell
,
Mousa Kharnaf
,
Farhan Zafar
,
Kyle W. Riggs
,
James A. Reagor
,
Brett P. Monia
,
Alexey S. Revenko
,
Daniel Leino
,
A. Phillip Owens
,
Janine Martin
,
Benjamin Gourley
,
Leah Rosenfeldt
,
Joseph S. Palumbo
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2022007586
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2022007586
Previous studies suggested that contact pathway factors drive thrombosis in mechanical circulation. We used a rabbit model of veno-arterial extracorporeal circulation (VA-ECMO) to evaluate the role of factors XI and XII in ECMO-associated thrombosis and organ damage. Factors XI and XII (FXI, FXII) were depleted using established antisense oligonucleotides before placement on a blood-primed VA-ECMO circuit. Decreasing FXII or FXI to < 5% of baseline activity significantly prolonged ECMO circuit lifespan, limited the development of coagulopathy, and prevented fibrinogen consumption. Histological analysis suggested that FXII depletion mitigated interstitial pulmonary edema and hemorrhage whereas heparin and FXI depletion did not. Neither FXI nor FXII depletion was associated with significant hemorrhage in other organs. In vitro analysis showed that membrane oxygenator fibers (MOFs) alone are capable of driving significant thrombin generation in a FXII- and FXI-dependent manner. MOFs also augment thrombin generation triggered by low (1 pM) or high (5 pM) tissue factor concentrations. However, only FXI elimination completely prevented the increase in thrombin generation driven by MOFs, suggesting MOFs augment thrombin-mediated FXI activation. Together, these results suggest that therapies targeting FXII or FXI limit thromboembolic complications associated with ECMO. Further studies are needed to determine the contexts wherein targeting FXI and FXII, either alone or in combination, would be most beneficial in ECMO. Moreover, studies are also needed to determine the potential mechanisms coupling FXII to end-organ damage in ECMO.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1182/bloodadvances.2022007586
- https://ashpublications.org/bloodadvances/article-pdf/7/8/1404/2045917/blooda_adv-2022-007586-main.pdf
- OA Status
- gold
- Cited By
- 17
- References
- 61
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4306194460
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4306194460Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1182/bloodadvances.2022007586Digital Object Identifier
- Title
-
Targeting the contact system in a rabbit model of extracorporeal membrane oxygenationWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-10-14Full publication date if available
- Authors
-
James S. Tweddell, Mousa Kharnaf, Farhan Zafar, Kyle W. Riggs, James A. Reagor, Brett P. Monia, Alexey S. Revenko, Daniel Leino, A. Phillip Owens, Janine Martin, Benjamin Gourley, Leah Rosenfeldt, Joseph S. PalumboList of authors in order
- Landing page
-
https://doi.org/10.1182/bloodadvances.2022007586Publisher landing page
- PDF URL
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https://ashpublications.org/bloodadvances/article-pdf/7/8/1404/2045917/blooda_adv-2022-007586-main.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://ashpublications.org/bloodadvances/article-pdf/7/8/1404/2045917/blooda_adv-2022-007586-main.pdfDirect OA link when available
- Concepts
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Extracorporeal membrane oxygenation, Factor XII, Medicine, Extracorporeal circulation, Thrombosis, Platelet, Thrombin, Internal medicine, Coagulation, CardiologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
17Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 6, 2023: 6Per-year citation counts (last 5 years)
- References (count)
-
61Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.only | 154 |
| abstract_inverted_index.role | 26 |
| abstract_inverted_index.that | 4, 84, 117, 177 |
| abstract_inverted_index.used | 14 |
| abstract_inverted_index.were | 44 |
| abstract_inverted_index.with | 107, 187 |
| abstract_inverted_index.(FXI, | 42 |
| abstract_inverted_index.ECMO. | 188, 212, 229 |
| abstract_inverted_index.FXII) | 43 |
| abstract_inverted_index.FXII, | 201 |
| abstract_inverted_index.FXII- | 132 |
| abstract_inverted_index.MOFs, | 166 |
| abstract_inverted_index.alone | 122, 203 |
| abstract_inverted_index.drive | 8 |
| abstract_inverted_index.edema | 90 |
| abstract_inverted_index.limit | 183 |
| abstract_inverted_index.model | 17 |
| abstract_inverted_index.organ | 36 |
| abstract_inverted_index.other | 111 |
| abstract_inverted_index.these | 174 |
| abstract_inverted_index.using | 46 |
| abstract_inverted_index.vitro | 114 |
| abstract_inverted_index.would | 207 |
| abstract_inverted_index.(MOFs) | 121 |
| abstract_inverted_index.before | 50 |
| abstract_inverted_index.damage | 227 |
| abstract_inverted_index.driven | 164 |
| abstract_inverted_index.either | 202 |
| abstract_inverted_index.factor | 151 |
| abstract_inverted_index.fibers | 120 |
| abstract_inverted_index.needed | 192, 217 |
| abstract_inverted_index.rabbit | 16 |
| abstract_inverted_index.showed | 116 |
| abstract_inverted_index.tissue | 150 |
| abstract_inverted_index.Factors | 38 |
| abstract_inverted_index.Further | 189 |
| abstract_inverted_index.Neither | 100 |
| abstract_inverted_index.VA-ECMO | 55 |
| abstract_inverted_index.augment | 138, 169 |
| abstract_inverted_index.capable | 124 |
| abstract_inverted_index.circuit | 70 |
| abstract_inverted_index.contact | 5 |
| abstract_inverted_index.damage. | 37 |
| abstract_inverted_index.driving | 126 |
| abstract_inverted_index.factors | 7, 28 |
| abstract_inverted_index.heparin | 94 |
| abstract_inverted_index.limited | 72 |
| abstract_inverted_index.manner. | 135 |
| abstract_inverted_index.organs. | 112 |
| abstract_inverted_index.pathway | 6 |
| abstract_inverted_index.results | 175 |
| abstract_inverted_index.studies | 2, 190, 214 |
| abstract_inverted_index.suggest | 176 |
| abstract_inverted_index.whereas | 93 |
| abstract_inverted_index.wherein | 197 |
| abstract_inverted_index.&lt; | 62 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.However, | 153 |
| abstract_inverted_index.Previous | 1 |
| abstract_inverted_index.activity | 66 |
| abstract_inverted_index.analysis | 82, 115 |
| abstract_inverted_index.baseline | 65 |
| abstract_inverted_index.circuit. | 56 |
| abstract_inverted_index.contexts | 196 |
| abstract_inverted_index.coupling | 223 |
| abstract_inverted_index.depleted | 45 |
| abstract_inverted_index.evaluate | 24 |
| abstract_inverted_index.increase | 160 |
| abstract_inverted_index.membrane | 118 |
| abstract_inverted_index.thrombin | 128, 139, 162 |
| abstract_inverted_index.(VA-ECMO) | 22 |
| abstract_inverted_index.Moreover, | 213 |
| abstract_inverted_index.Together, | 173 |
| abstract_inverted_index.antisense | 48 |
| abstract_inverted_index.depletion | 86, 97, 104 |
| abstract_inverted_index.determine | 194, 219 |
| abstract_inverted_index.end-organ | 226 |
| abstract_inverted_index.lifespan, | 71 |
| abstract_inverted_index.mitigated | 87 |
| abstract_inverted_index.placement | 51 |
| abstract_inverted_index.potential | 221 |
| abstract_inverted_index.prevented | 78, 158 |
| abstract_inverted_index.prolonged | 68 |
| abstract_inverted_index.pulmonary | 89 |
| abstract_inverted_index.suggested | 3, 83 |
| abstract_inverted_index.targeting | 179, 198 |
| abstract_inverted_index.therapies | 178 |
| abstract_inverted_index.triggered | 141 |
| abstract_inverted_index.Decreasing | 57 |
| abstract_inverted_index.associated | 106, 186 |
| abstract_inverted_index.beneficial | 210 |
| abstract_inverted_index.completely | 157 |
| abstract_inverted_index.fibrinogen | 79 |
| abstract_inverted_index.generation | 129, 140, 163 |
| abstract_inverted_index.hemorrhage | 92, 109 |
| abstract_inverted_index.mechanical | 11 |
| abstract_inverted_index.mechanisms | 222 |
| abstract_inverted_index.oxygenator | 119 |
| abstract_inverted_index.suggesting | 167 |
| abstract_inverted_index.thrombosis | 9, 34 |
| abstract_inverted_index.activation. | 172 |
| abstract_inverted_index.circulation | 21 |
| abstract_inverted_index.development | 74 |
| abstract_inverted_index.elimination | 156 |
| abstract_inverted_index.established | 47 |
| abstract_inverted_index.significant | 108, 127 |
| abstract_inverted_index.Histological | 81 |
| abstract_inverted_index.blood-primed | 54 |
| abstract_inverted_index.circulation. | 12 |
| abstract_inverted_index.combination, | 206 |
| abstract_inverted_index.consumption. | 80 |
| abstract_inverted_index.interstitial | 88 |
| abstract_inverted_index.FXI-dependent | 134 |
| abstract_inverted_index.coagulopathy, | 76 |
| abstract_inverted_index.complications | 185 |
| abstract_inverted_index.significantly | 67 |
| abstract_inverted_index.veno-arterial | 19 |
| abstract_inverted_index.extracorporeal | 20 |
| abstract_inverted_index.thromboembolic | 184 |
| abstract_inverted_index.ECMO-associated | 33 |
| abstract_inverted_index.concentrations. | 152 |
| abstract_inverted_index.oligonucleotides | 49 |
| abstract_inverted_index.thrombin-mediated | 170 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 97 |
| corresponding_author_ids | https://openalex.org/A5113790181 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 13 |
| corresponding_institution_ids | https://openalex.org/I1285204247, https://openalex.org/I63135867 |
| citation_normalized_percentile.value | 0.91415897 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |