Key Points
- To determine whether ristocetin- or botrocetin-induced binding of von Willebrand factor to platelet glycoprotein Ibα more accurately models shear-stress-dependent interactions.
- Screened a panel of anti-von Willebrand factor (vWF) and anti-GP Ibα antibodies with known effects on ristocetin- and botrocetin-dependent binding.
- Measured antibody inhibition of Chinese hamster ovary cells expressing recombinant GP Ibα adhering to surface-immobilized vWF under hydrodynamic flow.
- Evaluated the capacity of the antibodies to block shear-stress-induced platelet aggregation.
- Shear-dependent interactions between vWF and GP Ibα correlated strongly with ristocetin-dependent, rather than botrocetin-dependent, binding under static conditions.
- Specific anti-vWF monoclonal antibodies selectively inhibited shear-dependent platelet aggregation.
Structured PICO
PPopulationChinese hamster ovary cells expressing recombinant GP Ibalpha and platelets
IInterventionPanel of anti-vWF and anti-GP Ibalpha antibodies
OOutcomeInhibition of adhesion of Chinese hamster ovary cells to surface-associated vWF under hydrodynamic flow or shear-stress-induced platelet aggregationsurrogate
This preclinical study demonstrates that shear-dependent vWF-platelet interactions correlate with ristocetin-dependent binding, providing mechanistic insights into thrombosis and potential therapeutic targets.