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Updated: Jun 5, 2026
04:32
A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
Published on: June 5, 2019
Histidine‑rich Glycoprotein Modulates Platelet Adhesion and Aggregation by Binding to GPIbα and GPIIb/IIIa
Rida Malik1, Ji Zhou2, Miguel A D Neves3
1McMaster University | Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
Blood
|June 4, 2026
Summary
Histidine-rich glycoprotein (HRG) regulates platelet function by binding to key receptors, inhibiting adhesion and aggregation. Lower HRG levels in sepsis and COVID-19 patients correlate with hyperreactive platelets.
Area of Science:
- Hematology
- Biochemistry
- Molecular Biology
Background:
- Histidine-rich glycoprotein (HRG) is a plasma protein known to modulate the contact system.
- HRG's role in platelet biology, despite its presence on platelet surfaces, was previously unclear.
- Understanding HRG's interaction with platelet receptors is crucial for elucidating its function in hemostasis and thrombosis.
Purpose of the Study:
- To investigate the direct engagement of HRG with platelet receptors.
- To determine HRG's effect on platelet adhesion, aggregation, and thrombus formation.
- To explore the clinical relevance of HRG levels in inflammatory conditions.
Main Methods:
- Utilized human and murine platelets for in vitro experiments.
- Employed binding assays to assess HRG interaction with glycoprotein (GP)Ibα and GPIIb/IIIa.
- Performed flow-based assays and microperfusion chambers to evaluate platelet function under shear stress.
- Analyzed plasma HRG levels in patients with sepsis and COVID-19.
Main Results:
- HRG binds to GPIbα on resting and activated platelets and to GPIIb/IIIa on activated platelets.
- HRG competitively inhibits von Willebrand factor (VWF) and fibrinogen binding to their respective platelet receptors.
- HRG attenuates platelet agglutination, aggregation, VWF-mediated platelet string formation, and thrombus growth under high shear.
- Reduced plasma HRG levels in sepsis and COVID-19 patients were associated with a hyperreactive platelet phenotype in vitro.
Conclusions:
- HRG directly modulates platelet adhesion and aggregation by interacting with GPIbα and GPIIb/IIIa.
- HRG acts as an endogenous inhibitor of platelet activation, competing with VWF and fibrinogen.
- HRG deficiency contributes to platelet hyperreactivity, suggesting a role in thrombotic complications of sepsis and COVID-19.
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