Evidence map›Paper›PMID 32369849›Full record

ArticleThrombosis and haemostasis2020

Platelet Activation via Shear Stress Exposure Induces a Differing Pattern of Biomarkers of Activation versus Biochemical Agonists.

Yana Roka-Moiia, Ryan Walk, Daniel E Palomares, Kaitlyn R Ammann, Annalisa Dimasi, Joseph E Italiano, Jawaad Sheriff, Danny Bluestein, Marvin J Slepian

Open access · greenAbstract readComparative Study
In one paragraph

Article in Thrombosis and haemostasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
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  6. Platelet Disorders and Medication Strategies.Thrombosis and haemostasis · 2026
    Review
  7. Key markers and detection methods for evaluating platelet dysfunction in mechanical circulatory support devices.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2025
    Review
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  17. Procoagulant platelets: novel players in thromboinflammation.American journal of physiology. Cell physiology · 2022
    Review
  18. 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

9 authors at 4 institutions in 2 countries.

Yana Roka-MoiiaDepartment of Medicine, Sarver Heart Center, University of Arizona, Tucson, Arizona, United States.
Ryan WalkDepartment of Medicine, Sarver Heart Center, University of Arizona, Tucson, Arizona, United States.
Daniel E PalomaresDepartment of Medicine, Sarver Heart Center, University of Arizona, Tucson, Arizona, United States.
Kaitlyn R AmmannDepartment of Medicine, Sarver Heart Center, University of Arizona, Tucson, Arizona, United States.
Annalisa DimasiDepartment of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
Joseph E ItalianoBrigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Jawaad SheriffDepartment of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States.
Danny BluesteinDepartment of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States.
Marvin J SlepianDepartment of Medicine, Sarver Heart Center, University of Arizona, Tucson, Arizona, United States.
University of Arizona · USStony Brook University · USHarvard University · USPolitecnico di Milano · IT

Funding

Optimizing Cardiovascular Device Thromboresistance for Eliminating AnticoagulantsU01EB012487 · NIBIB · STATE UNIVERSITY NEW YORK STONY BROOK · PI BLUESTEIN, DANNY · 2010 to 2014
$6.9M
Cardiovascular Biomedical Engineering Training GrantT32HL007955 · NHLBI · UNIVERSITY OF ARIZONA · PI BARTON, JENNIFER KEHLET · 2001 to 2020
$5.1M
Multiscale Modeling of Blood Flow and Platelet Mediated ThrombosisU01HL131052 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI BLUESTEIN, DANNY · 2016 to 2020
$3.6M
NHLBI NIH HHS T32 HL007955NHLBI NIH HHS U01 HL131052NIBIB NIH HHS U01 EB012487U01 EB012487 National Institute of HealthU01 HL131052 National Institute of Health
6 · The paper itself

Abstract

backgroundImplantable cardiovascular therapeutic devices, while hemodynamically effective, remain limited by thrombosis. A driver of device-associated thrombosis is shear-mediated platelet activation (SMPA). Underlying mechanisms of SMPA, as well as useful biomarkers able to detect and discriminate mechanical versus biochemical platelet activation, are poorly defined. We hypothesized that SMPA induces a differing pattern of biomarkers compared with biochemical agonists.

methodsGel-filtered human platelets were subjected to mechanical activation via either uniform constant or dynamic shear; or to biochemical activation by adenosine diphosphate (ADP), thrombin receptor-activating peptide 6 (TRAP-6), thrombin, collagen, epinephrine, or arachidonic acid. Markers of platelet activation (P-selectin, integrin αIIbβ3 activation) and apoptosis (mitochondrial membrane potential, caspase 3 activation, and phosphatidylserine externalization [PSE]) were examined using flow cytometry. Platelet procoagulant activity was detected by chromogenic assay measuring thrombin generation. Contribution of platelet calcium flux in SMPA was tested employing calcium chelators, ethylenediaminetetraacetic acid (EDTA), and BAPTA-AM.

resultsPlatelet exposure to continuous shear stress, but not biochemical agonists, resulted in a dramatic increase of PSE and procoagulant activity, while no integrin αIIbβ3 activation occurred, and P-selectin levels remained barely elevated. SMPA was associated with dissipation of mitochondrial membrane potential, but no caspase 3 activation was observed. Shear-mediated PSE was significantly decreased by chelation of extracellular calcium with EDTA, while intracellular calcium depletion with BAPTA-AM had no significant effect. In contrast, biochemical agonists ADP, TRAP-6, arachidonic acid, and thrombin were potent inducers of αIIbβ3 activation and/or P-selectin exposure. This differing pattern of biomarkers seen for SMPA for continuous uniform shear was replicated in platelets exposed to dynamic shear stress via circulation through a ventricular assist device-propelled circulatory loop.

conclusionElevated shear stress, but not biochemical agonists, induces a differing pattern of platelet biomarkers-with enhanced PSE and thrombin generation on the platelet surface. This differential biomarker phenotype of SMPA offers the potential for early detection and discrimination from that mediated by biochemical agonists.

Indexed as

Mechanotransduction, CellularApoptosisBiomarkersBlood CoagulationBlood PlateletsCalcium SignalingCaspase 3HumansMembrane Potential, MitochondrialPhosphatidylserinesPlatelet ActivationPlatelet Glycoprotein GPIIb-IIIa ComplexP-SelectinStress, MechanicalBiomarkersCASP3 protein, humanCaspase 3PhosphatidylserinesPlatelet Glycoprotein GPIIb-IIIa ComplexP-SelectinSELP protein, human

Identifiers

PMID32369849
PMCPMC8577487
OpenAlexW3023733258

What OpenQuestion 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 OpenQuestion graph.