Under the high shear stress conditions characteristic of mechanical circulatory support devices, free Hb binds to VWF and increases the affinity of the VWF multimers for the GPIb receptor on the surface of platelets. This interaction allows a massive binding of platelets to surfaces coated with fibrinogen or VWF. Because free Hb levels are elevated in the blood of patients with mechanical circulatory support devices as a result of hemodynamic perturbations, the interaction between free Hb and VWF may contribute to the development of thrombi by boosting platelet binding and aggregation at the surface of the circulatory support device that is coated with adsorbed fibrinogen. Illustration by Sart-Bernard Studios.