Evidence map›Paper›PMID 25931587›Full record

ArticleBlood2015

Resolving the multifaceted mechanisms of the ferric chloride thrombosis model using an interdisciplinary microfluidic approach.

Jordan C Ciciliano, Yumiko Sakurai, David R Myers, Meredith E Fay, Beatrice Hechler, Shannon Meeks, Renhao Li, J Brandon Dixon, L Andrew Lyon, Christian Gachet and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

54 citing papers in PubMed, 84 citations in OpenAlex.

  1. Review
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  11. Engineering Organ-on-a-Chip Systems for Vascular Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2023
    Review
  12. Article
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  14. Review
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  18. State of the art in cerebral venous sinus thrombosis animal models.Journal of thrombosis and haemostasis : JTH · 2022
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Jordan C CicilianoWoodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA; Wallace C Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA; Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA;
Yumiko SakuraiWallace C Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA; Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA;
David R MyersWallace C Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA; Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA;
Meredith E FayWallace C Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA; Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA;
Beatrice HechlerINSERM, Unité Mixte de Recherche S949, Etablissement Français du Sang-Alsace, Université de Strasbourg, Strasbourg, France; and.
Shannon MeeksAflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA;
Renhao LiAflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA;
J Brandon DixonWoodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA; Wallace C Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA;
L Andrew LyonSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA.
Christian GachetINSERM, Unité Mixte de Recherche S949, Etablissement Français du Sang-Alsace, Université de Strasbourg, Strasbourg, France; and.
Wilbur A LamWallace C Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA; Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA;
Georgia Institute of Technology · USEmory University · USThe Wallace H. Coulter Department of Biomedical Engineering · USÉtablissement Français du Sang · FRInserm · FR

Funding

Translational Research SkillsU54HL112309 · NHLBI · EMORY UNIVERSITY · PI LOLLAR, JOHN S. · 2012 to 2016
$12.1M
Cellular and Molecular Mechanisms of Acute Lung Injury in Sickle Cell DiseaseU01HL117721 · NHLBI · EMORY UNIVERSITY · PI DEBAUN, MICHAEL R., JOINER, CLINTON H · 2013 to 2017
$9.4M
Endothelialized microfluidics for sickle cell disease research & drug discoveryR01HL121264 · NHLBI · EMORY UNIVERSITY · PI LAM, WILBUR A · 2014 to 2018
$2.0M
NHLBI NIH HHS R01 HL121264NHLBI NIH HHS R01-HL121264NHLBI NIH HHS U01 HL117721NHLBI NIH HHS U01-HL117721NHLBI NIH HHS U54 HL112309NHLBI NIH HHS U54-HL112309
6 · The paper itself

Abstract

The mechanism of action of the widely used in vivo ferric chloride (FeCl3) thrombosis model remains poorly understood; although endothelial cell denudation is historically cited, a recent study refutes this and implicates a role for erythrocytes. Given the complexity of the in vivo environment, an in vitro reductionist approach is required to systematically isolate and analyze the biochemical, mass transfer, and biological phenomena that govern the system. To this end, we designed an "endothelial-ized" microfluidic device to introduce controlled FeCl3 concentrations to the molecular and cellular components of blood and vasculature. FeCl3 induces aggregation of all plasma proteins and blood cells, independent of endothelial cells, by colloidal chemistry principles: initial aggregation is due to binding of negatively charged blood components to positively charged iron, independent of biological receptor/ligand interactions. Full occlusion of the microchannel proceeds by conventional pathways, and can be attenuated by antithrombotic agents and loss-of-function proteins (as in IL4-R/Iba mice). As elevated FeCl3 concentrations overcome protective effects, the overlap between charge-based aggregation and clotting is a function of mass transfer. Our physiologically relevant in vitro system allows us to discern the multifaceted mechanism of FeCl3-induced thrombosis, thereby reconciling literature findings and cautioning researchers in using the FeCl3 model.

Indexed as

AspirinBiomechanical PhenomenaBlood PlateletsCell AggregationChloridesErythrocytesFerric CompoundsFibrinolytic AgentsHeparinHumansMicrofluidic Analytical TechniquesModels, BiologicalPlatelet-Rich PlasmaPrimary Cell CultureProtein AggregatesProtein BindingAspirinChloridesferric chlorideFerric CompoundsFibrinolytic AgentsHeparinProtein Aggregates

Identifiers

PMID25931587
PMCPMC4528067
OpenAlexW1991585575

What OpenQuestion holds

Textmetadata
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.