Efficiency of Platelet Adhesion to Fibrinogen Depends on both Cell Activation and Flow

AbstractThe kinetics of adhesion of platelets to fibrinogen (Fg) immobilized on polystyrene latex beads (Fg-beads) was determined in suspensions undergoing Couette flow at well-defined homogeneous shear rates. The efficiency of platelet adhesion to Fg-beads was compared for ADP-activated versus “resting” platelets. The effects of the shear rate (100–2000s−1), Fg density on the beads (24–2882Fg/μm2), the concentration of ADP used to activate the platelets, and the presence of soluble fibrinogen were assessed. “Resting” platelets did not specifically adhere to Fg-beads at levels detectable with our methodology. The apparent efficiency of platelet adhesion to Fg-beads readily correlated with the proportion of platelets “quantally” activated by doses of ADP, i.e., only ADP-activated platelets appeared to adhere to Fg-beads, with a maximal adhesion efficiency of 6–10% at shear rates of 100–300s−1, decreasing with increasing shear rates up to 2000s−1. The adhesion efficiency was found to decrease by only threefold when decreasing the density of Fg at the surface of the beads by 100-fold, with only moderate decreases in the presence of physiologic concentrations of soluble Fg. These adhesive interactions were also compared using activated GPIIbIIIa-coated beads. Our studies provide novel model particles for studying platelet adhesion relevant to hemostasis and thrombosis, and show how the state of activation of the platelet and the local flow conditions regulate Fg-dependent adhesion