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December 3, 2020Arteriosclerosis Thrombosis and Vascular BiologyOpen Access

Nonredundant Roles of Platelet Glycoprotein VI and Integrin αIIbβ3 in Fibrin-Mediated Microthrombus Formation

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Why the study?

Fibrin is considered to strengthen thrombus formation via integrin αIIbβ3, but recent findings indicate it can also act as a ligand for platelet glycoprotein VI.

Population

Whole blood flowed over immobilized fibrin surfaces, including blood from Glanzmann thrombasthenia

Comparison

Inhibition or absence of αIIbβ3, glycoprotein VI, or Syk vs uninhibited conditions

Design

In vitro microfluidics and suspension assay study

Authors

GPGina PerrellaUniversity College BirminghamJHJingnan HuangUniversity of Electronic Science and Technology of ChinaIPIsabella ProvenzaleMaastricht University Medical Centre

Discussion

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Implication

Fibrin may consolidate microthrombi via GPVI–αIIbβ3 interplay; leaves open whether dual inhibition alters clinical thrombosis risk.

Structured PICO

P
Population
Whole blood flowed at high shear rate (1000 s-1) over immobilized fibrin surfaces, including blood with Glanzmann thrombasthenia
I
Intervention
Blocking of glycoprotein VI (with Fab 9O12), inhibition of Syk, or absence of αIIbβ3
C
Comparator
Unblocked/normal conditions
O
Outcome
Platelet adhesion, activation (P-selectin expression), secretion, Ca2+ signaling, aggregation, and microthrombus formationsurrogate

Fibrin mediates microthrombus formation through nonredundant roles of platelet glycoprotein VI and integrin αIIbβ3, highlighting potential mechanistic targets for antithrombotic therapy.

Cite This Study

Perrella et al. (2020) studied this question.

synapsesocial.com/papers/6a72c0b7e5469ee92be28c8chttps://doi.org/10.1161/atvbaha.120.314641
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in Thrombus Formation on Collagen-Like Surfaces2019 · 47 citations
  2. 2Differential integrin activity mediated by platelet collagen receptor engagement under flow conditions2017 · 27 citations
  3. 3The Structure of a Full-length Membrane-embedded Integrin Bound to a Physiological Ligand2015 · 41 citations
  4. 4Key role of integrin αIIbβ3 signaling to Syk kinase in tissue factor-induced thrombin generation2012 · 40 citations
  5. 5Coated platelets function in platelet-dependent fibrin formation via integrin α IIb β 3 and transglutaminase factor XIII2015 · 73 citations