Evidence map›Paper›PMID 32110750›Full record

ArticleResearch and practice in thrombosis and haemostasis2020

Antibody inhibition of contact factor XII reduces platelet deposition in a model of extracorporeal membrane oxygenator perfusion in nonhuman primates.

Michael Wallisch, Christina U Lorentz, Hari H S Lakshmanan, Jennifer Johnson, Marschelle R Carris, Cristina Puy, David Gailani, Monica T Hinds, Owen J T McCarty, András Gruber and 1 more

Open access · goldAbstract read
In one paragraph

Article in Research and practice in thrombosis and haemostasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
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  11. Progress towards permanent respiratory support.Current opinion in organ transplantation · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Michael WallischDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.ORCID https://orcid.org/0000-0002-7133-795X
Christina U LorentzDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.ORCID https://orcid.org/0000-0002-6885-2352
Hari H S LakshmananDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.ORCID https://orcid.org/0000-0002-4258-9138
Jennifer JohnsonDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.
Marschelle R CarrisDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.
Cristina PuyDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.
David GailaniDepartment of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine Nashville TN USA.ORCID https://orcid.org/0000-0001-8142-8014
Monica T HindsDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.ORCID https://orcid.org/0000-0002-5267-3376
Owen J T McCartyDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.ORCID https://orcid.org/0000-0001-9481-0124
András GruberDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.ORCID https://orcid.org/0000-0001-6212-2247
Erik I TuckerDepartment of Biomedical Engineering Oregon Health & Science University Portland OR USA.
Oregon Health & Science University · USVanderbilt University · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Characterization of Coagulation Factor-platelet Interactions: Role of FXIR01HL101972 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Owen J McCarty · 2010 to 2026
$8.5M
Contact Pathway Activation on Vascular DevicesR01HL144113 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI HINDS, MONICA T, MCCARTY, OWEN J · 2018 to 2025
$6.0M
Biochemistry and Pathophysiology of Factor XI and Contact ActivationR35HL140025 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAILANI, DAVID · 2018 to 2024
$5.5M
HLS- Factor XII Inhibitor for Surface Initiated ThrombosisR44HL126235 · NHLBI · ARONORA, INC. · PI LORENTZ, CHRISTINA U, TUCKER, ERIK IAN · 2016 to 2022
$5.2M
NHLBI NIH HHS R01 HL101972NHLBI NIH HHS R01 HL144113NHLBI NIH HHS R35 HL140025NHLBI NIH HHS R44 HL126235NIH HHS P51 OD011092
6 · The paper itself

Abstract

backgroundThe contact factor XII (FXII) activates upon contact with a variety of charged surfaces. Activated FXII (FXIIa) activates factor XI, which activates factor IX, resulting in thrombin generation, platelet activation, and fibrin formation. In both in vitro and in vivo rabbit models, components of medical devices, including extracorporeal oxygenators, are known to incite fibrin formation in a FXII-dependent manner. Since FXII has no known role in hemostasis and its inhibition is therefore likely a safe antithrombotic approach, we investigated whether FXII inhibition also reduces accumulation of platelets in extracorporeal oxygenators.

objectivesWe aimed to determine the effect of FXII inhibition on platelet deposition in perfused extracorporeal membrane oxygenators in nonhuman primates.

methodsA potent FXII neutralizing monoclonal antibody, 5C12, was administered intravenously to block contact activation in baboons. Extracorporeal membrane oxygenators were temporarily deployed into chronic arteriovenous access shunts. Radiolabeled platelet deposition in oxygenators was quantified in real time using gamma camera imaging. Biochemical assays were performed to characterize the method of action of 5C12.

resultsThe anti-FXII monoclonal antibody 5C12 recognized both the alpha and beta forms of human and baboon FXII by binding to the protease-containing domain, and inhibited FXIIa activity. Administration of 5C12 to baboons reduced platelet deposition and fibrin formation in the extracorporeal membrane oxygenators, in both the presence and absence of systemic low-dose unfractionated heparin. The antiplatelet dose of 5C12 did not cause measurable increases in template bleeding times in baboons.

conclusionsFXII represents a possible therapeutic and safe target for reducing platelet deposition and fibrin formation during medical interventions including extracorporeal membrane oxygenation.

Indexed as

blood plateletextracorporeal membrane oxygenationfactor XIIhemostasisthrombosis

Identifiers

PMID32110750
PMCPMC7040549
OpenAlexW3005620645

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.