Introduction: Thromboembolic events caused by implanted vascular devices present serious medical challenges. In particular bileaflet mechanical heart valves (MHVs) are prone to thrombus formation in the hinge region due to a combination of high shear stress and stagnation regions. Most studies of shear-induced platelet activation and aggregation have been performed using viscometers, parallel plate flow, and other non-physiologic in vitro configurations. The present study investigated these events in a physiogically relevant environment in which thrombin formation in response to shear stress activation of platelets plays a more predominant role.
Materials and methods: Anticoagulated (citrated) human blood was placed in a steady flow loop containing a 400 microm round orifice or various MHVs in the leakage position. Simultaneous blood recalcification enhanced the thrombus forming potential of the blood. Aggrastat and AN51 were used to block binding to the platelet GPIIb/IIIa and GPIb receptors, respectively, and aspirin was used to block thromboxane production. Thrombin generation was measured indirectly by the thrombin-antithrombin III assay.
Results and conclusions: Aggrastat, AN51, and aspirin all suppressed thrombin formation. Furthermore, histological results suggested important roles for vWF and fibrinogen in a two-step model of thrombus formation. Thus, thrombin is reproducibly formed in this in vitro system, a process that can be suppressed by blocking platelet activation. This system has the potential to investigate mechanisms and interventions for medical devices that contact with blood under varying shear stress conditions.