Evidence map›Paper›PMID 34532631›Full record

ArticleResearch and practice in thrombosis and haemostasis2021

Quantitative 3D microscopy highlights altered von Willebrand factor α-granule storage in patients with von Willebrand disease with distinct pathogenic mechanisms.

Maurice Swinkels, Ferdows Atiq, Petra E Bürgisser, Johan A Slotman, Adriaan B Houtsmuller, Cilia de Heus, Judith Klumperman, Frank W G Leebeek, Jan Voorberg, Arend Jan Gerard Jansen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Research and practice in thrombosis and haemostasis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Clinical utility of panel-based genetic sequencing for von Willebrand disease.Research and practice in thrombosis and haemostasis · 2025
    Article
  3. Article
  4. Article
  5. Article
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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

11 authors at 3 institutions in 1 country.

Maurice SwinkelsDepartment of Hematology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.ORCID https://orcid.org/0000-0002-6667-9031
Ferdows AtiqDepartment of Hematology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.ORCID https://orcid.org/0000-0002-3769-9148
Petra E BürgisserDepartment of Hematology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.
Johan A SlotmanDepartment of Pathology Optical Imaging Center Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.ORCID https://orcid.org/0000-0001-9705-9620
Adriaan B HoutsmullerDepartment of Pathology Optical Imaging Center Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.ORCID https://orcid.org/0000-0003-0967-0740
Cilia de HeusDepartment of Cell Biology University Medical Center Utrecht The Netherlands.ORCID https://orcid.org/0000-0001-8618-8451
Judith KlumpermanDepartment of Cell Biology University Medical Center Utrecht The Netherlands.ORCID https://orcid.org/0000-0003-4835-6228
Frank W G LeebeekDepartment of Hematology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.ORCID https://orcid.org/0000-0001-5677-1371
Jan VoorbergMolecular and Cellular Hemostasis Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Center University of Amsterdam Amsterdam The Netherlands.ORCID https://orcid.org/0000-0003-4585-2621
Arend Jan Gerard JansenDepartment of Hematology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.ORCID https://orcid.org/0000-0002-2612-1420
Ruben BieringsDepartment of Hematology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.ORCID https://orcid.org/0000-0002-1205-9689
Erasmus MC · NLUniversity Medical Center Utrecht · NLSanquin · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPlatelets play a key role in hemostasis through plug formation and secretion of their granule contents at sites of endothelial injury. Defects in von Willebrand factor (VWF), a platelet α-granule protein, are implicated in von Willebrand disease (VWD), and may lead to defective platelet adhesion and/or aggregation. Studying VWF quantity and subcellular localization may help us better understand the pathophysiology of VWD.

objectiveQuantitative analysis of the platelet α-granule compartment and VWF storage in healthy individuals and VWD patients. PATIENTS/

methodsStructured illumination microscopy (SIM) was used to study VWF content and organization in platelets of healthy individuals and patients with VWD in combination with established techniques.

resultsSIM capably quantified clear morphological and granular changes in platelets stimulated with proteinase-activated receptor 1 (PAR-1) activating peptide and revealed a large intra- and interdonor variability in VWF-positive object numbers within healthy resting platelets, similar to variation in secreted protein acidic and rich in cysteine (SPARC). We subsequently characterized VWD platelets to identify changes in the α-granule compartment of patients with different VWF defects, and were able to stratify two patients with type 3 VWD rising from different pathological mechanisms. We further analyzed VWF storage in α-granules of a patient with homozygous

conclusionsOur findings highlight the utility of quantitative imaging approaches in assessing platelet granule content, which may help to better understand VWF storage in α-granules and to gain new insights in the etiology of VWD.

Indexed as

blood plateletsoptical imagingtype 3von Willebrand diseasevon Willebrand factor

Identifiers

PMID34532631
PMCPMC8440947
OpenAlexW3200168546

What Socratic holds

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Registered trials

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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 Socratic graph.