Evidence map›Paper›PMID 34552086›Full record

ArticleNature communications2021

Identification of the factor XII contact activation site enables sensitive coagulation diagnostics.

Marco Heestermans, Clément Naudin, Reiner K Mailer, Sandra Konrath, Kristin Klaetschke, Anne Jämsä, Maike Frye, Carsten Deppermann, Giordano Pula, Piotr Kuta and 10 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.8field-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

19 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Crystal structure of coagulation factor XII N-terminal domains 1-5.Acta crystallographica. Section D, Structural biology · 2025
    Article
  5. A brief comparison of human factor XII-AlaResearch and practice in thrombosis and haemostasis · 2025
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Dysregulated haemostasis in thrombo-inflammatory disease.Clinical science (London, England : 1979) · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Article
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

20 authors at 7 institutions in 6 countries.

Marco Heestermans *Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-5788-6653
Clément Naudin *Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-6777-9587
Reiner K Mailer *Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sandra KonrathInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Kristin KlaetschkeInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anne JämsäKarolinska University Hospital, Stockholm, Sweden.
Maike FryeInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-6257-7636
Carsten DeppermannInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Giordano PulaInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Piotr KutaInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Manuel A FrieseInstitute for Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0001-6380-2420
Mathias GelderblomDepartment of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Albert SickmannLeibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.
Roger J S PrestonIrish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
Jerzy-Roch NoferInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Stefan Rose-JohnInstitute of Biochemistry, University of Kiel, Kiel, Germany.ORCID 0000-0002-7519-3279
Lynn M ButlerInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ophira SalomonInstitute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.
Evi X StavrouDepartment of Medicine, Louis Stokes Veterans Administration Medical Center, Cleveland, OH, USA.ORCID 0000-0002-6075-7609
Thomas RennéInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. thomas@renne.net.ORCID 0000-0003-4594-5975
Universität Hamburg · DEChristian-Albrechts-Universität zu Kiel · DEKarolinska University Hospital · SELeibniz Institute for Analytical Sciences - ISAS · DELouis Stokes Cleveland VA Medical Center · USRoyal College of Surgeons in Ireland · IESheba Medical Center · IL

Funding

Targeted Abrogation of the FXII-uPAR-pAkt2 Axis in Neutrophils for Treatment of Chronic WoundsR01HL137695 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI STAVROU, EVI X. · 2019 to 2023
$2.0M
Treatment of Deep Vein Thrombosis via Targeted Inhibition of the FXII-uPAR-pAkt2 Axis in NeutrophilsI01BX003851 · VA · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · PI Evi X. Stavrou · 2020 to 2026
–
BLRD VA I01 BX003851NHLBI NIH HHS R01 HL137695
6 · The paper itself

Abstract

Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317-Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation. Peptides spanning these 23 residues competed with surface-induced FXII activation. Although FXII mutants lacking residues Gln317-Ser339 were susceptible to activation by plasmin and plasma kallikrein, they were ineffective in supporting arterial and venous thrombus formation in mice. Antibodies raised against the Gln317-Ser339 region induced FXII activation and triggered controllable contact activation in solution leading to thrombin generation by the intrinsic pathway of coagulation. The antibody-activated aPTT allows for standardization of particulate aPTT reagents and for sensitive monitoring of coagulation factors VIII, IX, XI.

Indexed as

Blood CoagulationAmino Acid SequenceAnimalsAntibodiesBlood PlateletsFactor XIIFactor XIIaMiceMutationPartial Thromboplastin TimePeptidesThrombosisAntibodiesFactor XIIFactor XIIaPeptides

Identifiers

PMID34552086
PMCPMC8458485
OpenAlexW3201610863

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.