Evidence map›Paper›PMID 21255247›Full record

ArticleJournal of thrombosis and haemostasis : JTH2011

The septic milieu triggers expression of spliced tissue factor mRNA in human platelets.

M T Rondina, H Schwertz, E S Harris, B F Kraemer, R A Campbell, N Mackman, C K Grissom, A S Weyrich, G A Zimmerman

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01735565 (Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplant), which is not on this map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.0field-weighted citation impact, top 4% 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.

NCT01735565 completednot on this mapstarted 2012, after this paper: background citation

Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplant

TypeobservationalSponsorUniversity of UtahRan2012 to 2016Enrolled23ConditionsBone Marrow Transplant
3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 134 citations in OpenAlex.

  1. Trial
  2. Angiopoietin 2 Levels in the Risk Stratification and Mortality Outcome Prediction of Sepsis-Associated Coagulopathy.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018
    Trial
  3. Review
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  13. A New Role of NAP1L1 in Megakaryocytes and Human Platelets.International journal of molecular sciences · 2022
    Article
  14. Review
  15. Article
  16. Review
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  19. Article
  20. Review

21 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 1 country.

M T RondinaDivision of General Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. matthew.rondina@hsc.utah.edu
H Schwertz
E S Harris
B F Kraemer
R A Campbell
N Mackman
C K Grissom
A S Weyrich
G A Zimmerman
University of Utah · USIntermountain Medical Center · USUniversity of North Carolina at Chapel Hill · US

Funding

University of Utah Center for Clinical and Translational ScienceUL1TR001067 · NCATS · UNIVERSITY OF UTAH · PI DERE, WILLARD H., HESS, RACHEL · 2013 to 2017
$19.8M
TRANSLATIONAL EVENTS IN PLATELETSR01HL066277 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S · 2001 to 2012
$3.8M
Molecular Interactions of Myeloid Cells with EndotheliumR37HL044525 · NHLBI · UNIVERSITY OF UTAH · PI ZIMMERMAN, GUY A. · 2004 to 2013
$3.5M
TISSUE FACTOR GENE REGULATION IN MONOCYTESR01HL048872 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MACKMAN, NIGEL · 1992 to 2009
$2.9M
Novel Thrombotic & Inflammatory Mechanisms of Venous Thromboembolism in ElderlyR01HL092746 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S · 2007 to 2010
$2.0M
Novel Activities of Platelets in Acute Lung InjuryR01HL091754 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S · 2008 to 2011
$1.5M
MOLECULAR INTERACTIONS OF MYELOID CELLS WITH ENDOTHELIUMR01HL044525 · NHLBI · UNIVERSITY OF UTAH · PI ZIMMERMAN, GUY A. · 1990 to 2003
$1.2M
Novel Thrombotic and Inflammatory Activities of Platelets in SepsisR01HL090870 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S, ZIMMERMAN, GUY A. · 2009 to 2010
$1.1M
Novel Platelet Functions in Sepsis and Venous ThromboembolismK23HL092161 · NHLBI · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2009 to 2013
$775k
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR011234 · NCRR · UNIVERSITY OF UTAH · PI MATSEN, JOHN M · 1995 to 1995
–
NCATS NIH HHS UL1 TR001067NCRR NIH HHS C06 RR011234NHLBI NIH HHS HL044525NHLBI NIH HHS HL048872NHLBI NIH HHS HL066277NHLBI NIH HHS HL090870NHLBI NIH HHS HL091754NHLBI NIH HHS HL092746NHLBI NIH HHS K23 HL092161NHLBI NIH HHS R01 HL044525NHLBI NIH HHS R01 HL048872NHLBI NIH HHS R01 HL066277NHLBI NIH HHS R01 HL090870NHLBI NIH HHS R01 HL091754NHLBI NIH HHS R01 HL092746NHLBI NIH HHS R37 HL044525PHS HHS K231440921PHS HHS ULI-RRO25764
6 · The paper itself

Abstract

backgroundActivated platelets have previously-unrecognized mechanisms of post-transcriptional gene expression that may influence hemostasis and inflammation. A novel pathway involves splicing of pre-mRNAs in resting platelets to mature, translatable mRNAs in response to cellular activation.

objectivesWe asked if bacterial products and host agonists present in the septic milieu induce tissue factor pre-mRNA splicing in platelets from healthy subjects. In parallel, we asked if spliced tissue factor (TF) mRNA is present in platelets from septic patients in a proof-of-principle analysis. PATIENTS/

methodsTF pre-mRNA and mRNA expression patterns were characterized in platelets from septic patients and in platelets isolated from healthy subjects activated with bacteria, toxins and inflammatory agonists. Procoagulant activity was also measured. RESULTS AND

conclusionsLive bacteria, staphylococcal α-toxin and lipopolysaccharide (LPS) induced TF pre-mRNA splicing in platelets isolated from healthy subjects. Toxin-stimulated platelets accelerated plasma clotting, a response that was blocked by a previously-characterized splicing inhibitor and by an anti-tissue factor antibody. Platelets from septic patients expressed spliced TF mRNA, whereas it was absent from unselected and age-matched control subjects. Tissue factor-dependent procoagulant activity was elevated in platelets from a subset of septic patients. Thus, bacterial and host factors induce splicing of TF pre-mRNA, expression of TF mRNA and tissue factor-dependent clotting activity in human platelets. TF mRNA is present in platelets from some septic patients, indicating that it may be a marker of altered platelet phenotype and function in sepsis and that splicing pathways are induced in this syndrome.

Indexed as

RNA SplicingBase SequenceBlood PlateletsDNA PrimersHumansRNA, MessengerSepsisDNA PrimersRNA, Messenger

Identifiers

PMID21255247
PMCPMC3071458
OpenAlexW1943527316

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Registered trials

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.