Evidence map›Paper›PMID 23293023›Full record

ArticleThe Journal of biological chemistry2013

Mechanical stability and fibrinolytic resistance of clots containing fibrin, DNA, and histones.

Colin Longstaff, Imre Varjú, Péter Sótonyi, László Szabó, Michael Krumrey, Armin Hoell, Attila Bóta, Zoltán Varga, Erzsébet Komorowicz, Krasimir Kolev

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02506985 (XENITH), which is not on this map. Cited by 145 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% 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.

NCT02506985 phase4terminatednot on this mapstarted 2015, after this paper: background citation

XENITH: Rivaroxaban for Pulmonary Embolism Managed With Catheter Directed Thrombolysis

TypeinterventionalSponsorSusan SmythRan2015 to 2016Enrolled10ConditionsPulmonary Embolism, Venous ThrombosisArmsrivaroxaban, warfarin
3 · Its place in the literature

Who cites it

145 citing papers in PubMed, 1 synthesis or guideline pooled it, 285 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Toward improved thrombolysis in ischemic stroke: targeting nonfibrin components.Research and practice in thrombosis and haemostasis · 2026
    Review
  11. Review
  12. Article
  13. Fibrin as a Versatile Fibrous Biopolymer.Sub-cellular biochemistry · 2026
    Review
  14. Beyond Direct Fibrinolysis: Novel Approaches to Thrombolysis.Pharmaceuticals (Basel, Switzerland) · 2025
    Review
  15. Article
  16. Review
  17. Article
  18. Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Article

85 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

10 authors at 6 institutions in 3 countries.

Colin LongstaffBiotherapeutics, Haemostasis Section, National Institute for Biological Standards and Control, South Mimms, Potters Bar EN6 3QG, United Kingdom. colin.longstaff@nibsc.hpa.org.uk
Imre Varjú
Péter Sótonyi
László Szabó
Michael Krumrey
Armin Hoell
Attila Bóta
Zoltán Varga
Erzsébet Komorowicz
Krasimir Kolev
Semmelweis University · HUHungarian Academy of Sciences · HUHelmholtz-Zentrum Berlin für Materialien und Energie · DEHUN-REN Research Centre for Natural Sciences · HUNational Institute for Biological Standards and Control · GBPhysikalisch-Technische Bundesanstalt · DE

Funding

Wellcome Trust 083174
6 · The paper itself

Abstract

Neutrophil extracellular traps are networks of DNA and associated proteins produced by nucleosome release from activated neutrophils in response to infection stimuli and have recently been identified as key mediators between innate immunity, inflammation, and hemostasis. The interaction of DNA and histones with a number of hemostatic factors has been shown to promote clotting and is associated with increased thrombosis, but little is known about the effects of DNA and histones on the regulation of fibrin stability and fibrinolysis. Here we demonstrate that the addition of histone-DNA complexes to fibrin results in thicker fibers (increase in median diameter from 84 to 123 nm according to scanning electron microscopy data) accompanied by improved stability and rigidity (the critical shear stress causing loss of fibrin viscosity increases from 150 to 376 Pa whereas the storage modulus of the gel increases from 62 to 82 pascals according to oscillation rheometric data). The effects of DNA and histones alone are subtle and suggest that histones affect clot structure whereas DNA changes the way clots are lysed. The combination of histones + DNA significantly prolongs clot lysis. Isothermal titration and confocal microscopy studies suggest that histones and DNA bind large fibrin degradation products with 191 and 136 nM dissociation constants, respectively, interactions that inhibit clot lysis. Heparin, which is known to interfere with the formation of neutrophil extracellular traps, appears to prolong lysis time at a concentration favoring ternary histone-DNA-heparin complex formation, and DNase effectively promotes clot lysis in combination with tissue plasminogen activator.

Indexed as

Blood CoagulationAnticoagulantsDeoxyribonucleasesDNAFibrinFibrinolysisGreen Fluorescent ProteinsHeparinHistonesMacromolecular SubstancesMicroscopy, ConfocalMicroscopy, Electron, ScanningNeutrophilsProtein StabilityScattering, Small AngleStress, MechanicalAnticoagulantsDeoxyribonucleasesDNAFibrinGreen Fluorescent ProteinsHeparinHistonesMacromolecular SubstancesTissue Plasminogen Activator

Identifiers

PMID23293023
PMCPMC3591605
OpenAlexW2135338217

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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.