Evidence map›Paper›PMID 26769048›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Coagulation Factor XI Promotes Distal Platelet Activation and Single Platelet Consumption in the Bloodstream Under Shear Flow.

Jevgenia Zilberman-Rudenko, Asako Itakura, Chantal P Wiesenekker, Ralf Vetter, Coen Maas, David Gailani, Erik I Tucker, András Gruber, Christoph Gerdes, Owen J T McCarty

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PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  9. Microfluidic endothelium-on-a-chip development, from in vivo to in vitro experimental models.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie · 2020
    Article
  10. The contact pathway and sepsis.Research and practice in thrombosis and haemostasis · 2019
    Review
  11. Review
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  13. Article
  14. Reporting Sex and Sex Differences in Preclinical Studies.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Article
  15. Effect of Pneumatic Tubing System Transport on Platelet Apheresis Units.Cardiovascular engineering and technology · 2018
    Article
  16. Article
  17. Review
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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

10 authors at 3 institutions in 2 countries.

Jevgenia Zilberman-RudenkoFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.). zilberma@ohsu.edu.
Asako ItakuraFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
Chantal P WiesenekkerFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
Ralf VetterFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
Coen MaasFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
David GailaniFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
Erik I TuckerFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
András GruberFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
Christoph GerdesFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
Owen J T McCartyFrom the Biomedical Engineering, School of Medicine (J.Z.-R., A.I., C.P.W., E.I.T., A.G., O.J.T.M.) and Division of Hematology (A.G., O.J.T.M.), Oregon Health & Science University, Portland; Pathology and Medicine, School of Medicine, Vanderbilt University, Nashville, TN (D.G.); Aronora Inc., Portland, OR (E.I.T., A.G.); Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (C.P.W., C.M.); and Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany (A.I., R.V., C.G.).
Vanderbilt University · USAronora (United States) · USUniversity Medical Center Utrecht · NL

Funding

Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
Characterization of Coagulation Factor-platelet Interactions: Role of FXIR01HL101972 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Owen J McCarty · 2010 to 2026
$8.5M
MECHANISMS OF TISSUE FACTOR/FACTOR VII ASSEMBLYR01HL047014 · NHLBI · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI MORRISSEY, JAMES H. · 1992 to 2016
$4.9M
Factor Xl in Vascular ThrombosisR01HL081326 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAILANI, DAVID · 2007 to 2017
$3.5M
FXI and SepsisR01GM116184 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI LUPU, FLOREA, MCCARTY, OWEN J · 2015 to 2018
$1.9M
NCATS NIH HHS UL1 TR000128NHLBI NIH HHS R01 HL047014NHLBI NIH HHS R01HL047014NHLBI NIH HHS R01 HL081326NHLBI NIH HHS R01 HL101972NHLBI NIH HHS R01HL101972NIGMS NIH HHS R01 GM116184NIGMS NIH HHS R01GM116184
6 · The paper itself

Abstract

objectiveCoagulation factor XI (FXI) has been shown to contribute to thrombus formation on collagen or tissue factor-coated surfaces in vitro and in vivo by enhancing thrombin generation. Whether the role of the intrinsic pathway of coagulation is restricted to the local site of thrombus formation is unknown. This study was aimed to determine whether FXI could promote both proximal and distal platelet activation and aggregate formation in the bloodstream. APPROACH AND

resultsPharmacological blockade of FXI activation or thrombin activity in blood did not affect local platelet adhesion, yet reduced local platelet aggregation, thrombin localization, and fibrin formation on immobilized collagen and tissue factor under shear flow, ex vivo. Downstream of the thrombus formed on immobilized collagen or collagen and 10 pmol/L tissue factor, platelet CD62P expression, microaggregate formation, and progressive platelet consumption were significantly reduced in the presence of FXI function-blocking antibodies or a thrombin inhibitor in a shear rate- and time-dependent manner. In a non-human primate model of thrombus formation, we found that inhibition of FXI reduced single platelet consumption in the bloodstream distal to a site of thrombus formation.

conclusionsThis study demonstrates that the FXI-thrombin axis contributes to distal platelet activation and procoagulant microaggregate formation in the blood flow downstream of the site of thrombus formation. Our data highlight FXI as a novel therapeutic target for inhibiting distal platelet consumption without affecting proximal platelet adhesion.

Indexed as

Blood CoagulationMechanotransduction, CellularPlatelet ActivationAnimalsBlood PlateletsCollagenDisease Models, AnimalFactor XIFactor XIaFibrinHumansMalePapio anubisPlatelet AggregationP-SelectinRegional Blood FlowCollagenFactor XIFactor XIaFibrinP-SelectinSELP protein, humanThrombinThromboplastinblood coagulationblood plateletsfactor XIhemodynamicsplatelet activation

Identifiers

PMID26769048
PMCPMC4767639
OpenAlexW2238151523

What OpenQuestion holds

Textmetadata
LicenceTDM
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.