Evidence map›Paper›PMID 30152919›Full record

ArticleJournal of thrombosis and haemostasis : JTH2018

Enhanced activity of an ADAMTS-13 variant (R568K/F592Y/R660K/Y661F/Y665F) against platelet agglutination in vitro and in a murine model of acute ischemic stroke.

K South, F Denorme, I I Salles-Crawley, S F De Meyer, D A Lane

Open access · hybridAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Toward improved thrombolysis in ischemic stroke: targeting nonfibrin components.Research and practice in thrombosis and haemostasis · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Mechanisms of ADAMTS13 regulation.Journal of thrombosis and haemostasis : JTH · 2022
    Review
  7. Article
  8. Article
  9. Rare Defects: Looking at the Dark Face of the Thrombosis.International journal of environmental research and public health · 2021
    Review
  10. Review
  11. Article
  12. Review
  13. 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

5 authors at 4 institutions in 2 countries.

K SouthCentre for Haematology, Imperial College London, London, UK.
F DenormeLaboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
I I Salles-CrawleyCentre for Haematology, Imperial College London, London, UK.
S F De MeyerLaboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
D A LaneCentre for Haematology, Imperial College London, London, UK.
Imperial College London · GBKU Leuven · BEResearch Institute for Chromatography · BEUniversity of Manchester · GB

Funding

PATHOPHYSIOLOGY OF CONSTITUTIVE A 1B-ADRENOCEPTOR ACTIONF32HL010004 · NHLBI · CLEVELAND CLINIC FOUNDATION · PI ZUSCIK, MICHAEL J · 1998 to 2000
$44k
DIETARY CHLORIDE AND SODIUM-DEPENDENT HYPERTENSIONK08HL001490 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI KURTZ, THEODORE W · 1985 to 1989
–
British Heart Foundation FS/10/004/28165British Heart Foundation PG/12/55/29740British Heart Foundation PG/14/87/31181British Heart Foundation PG/14/90/31219British Heart Foundation PG/17/42/33039
6 · The paper itself

Abstract

Essentials ADAMTS13 requires a substrate-induced conformational change to attain full activity in vitro. The efficacy of wild type ADAMTS13 in models of thrombosis/stroke may be enhanced by pre-activation. A pre-activated ADAMTS13 variant exhibits enhanced proteolysis of platelet agglutinates. This ADAMTS13 variant is protective in a murine model of stroke at a lower dose than WT ADAMTS13. SUMMARY: Background ADAMTS-13 circulates in a closed conformation, only achieving full proteolytic activity against von Willebrand factor (VWF) following a substrate-induced conformational change. A gain-of-function (GoF) ADAMTS-13 variant (R568K/F592Y/R660K/Y661F/Y665F) is conformationally preactivated. Objectives To establish how the hyperactivity of GoF ADAMTS-13 is manifested in experimental models mimicking the occlusive arterial thrombi present in acute ischemic stroke. Methods The ability of GoF ADAMTS-13 to dissolve VWF-platelet agglutinates was examined with an assay of ristocetin-induced platelet agglutination and in parallel-flow models of arterial thrombosis. A murine model of focal ischemia was used to assess the thrombolytic potential of GoF ADAMTS-13. Results Wild-type (WT) ADAMTS-13 required conformational activation to attain full activity against VWF-mediated platelet capture under flow. In this assay, GoF ADAMTS-13 had an EC

Indexed as

Platelet AggregationADAMTS13 ProteinAnimalsArteriesBlood PlateletsBrain IschemiaCHO CellsCricetinaeCricetulusDisease Models, AnimalHumansMiceProtein ConformationProteolysisRecombinant ProteinsRistocetinADAMTS13 ProteinADAMTS13 protein, humanADAMTS13 protein, mouseRecombinant ProteinsRistocetinADAMTS-13 proteinconformational activationhemostasisstrokevon Willebrand factor

Identifiers

PMID30152919
PMCPMC6282751
OpenAlexW2888828550

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.