Histidine-rich glycoprotein modulates platelet adhesion and aggregation by binding to GPIbα and GPIIb/IIIa.

Histidine-rich glycoprotein (HRG) inhibits platelet adhesion and aggregation by binding to GPIbα and GPIIb/IIIa, reducing thrombus formation under high-shear conditions.

• Why it matters: Understanding how HRG regulates platelet function is crucial because its deficiency is linked to hyperreactive platelets, which can contribute to thrombotic diseases, especially in conditions like sepsis and COVID-19.
• What they did: Researchers used human and murine platelets to examine HRG's interactions, demonstrating that HRG binds to GPIbα and GPIIb/IIIa, competing with von Willebrand factor and fibrinogen, and reducing platelet aggregation and thrombus growth.
• The result: Lower plasma HRG levels in sepsis and COVID-19 patients correlate with increased platelet reactivity, suggesting HRG's potential as a therapeutic target to modulate thrombotic risk.