title: Platelet activation due to hemodynamic shear stresses: damage accumulation model and comparison to in vitro measurements.
abstract: The need to optimize the thrombogenic performance of blood recirculating cardiovascular devices, e.g., prosthetic heart valves (PHV) and ventricular assist devices (VAD), is accentuated by the fact that most of them require lifelong anticoagulation therapy that does not eliminate the risk of thromboembolic complications. The formation of thromboemboli in the flow field of these devices is potentiated by contact with foreign surfaces and regional flow phenomena that stimulate blood clotting, especially platelets. With the lack of appropriate methodology, device manufacturers do not specifically optimize for thrombogenic performance. Such optimization can be facilitated by formulating a robust numerical methodology with predictive capabilities of flow-induced platelet activation. In this study, a phenomenological model for platelet cumulative damage, identified by means of genetic algorithms (GAs), was correlated with in vitro experiments conducted in a Hemodynamic Shearing Device (HSD). Platelets were uniformly exposed to flow shear representing the lower end of the stress levels encountered in devices, and platelet activity state (PAS) was measured in response to six dynamic shear stress waveforms representing repeated passages through a device, and correlated to the predictions of the damage accumulation model. Experimental results demonstrated an increase in PAS with a decrease in "relaxation" time between pulses. The model predictions were in very good agreement with the experimental results.
authors.affiliation: Department of Bioengineering, Politecnico di Milano, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Nobili
authors.forename: Jawaad
authors.initials: J
authors.lastname: Sheriff
authors.forename: Umberto
authors.initials: U
authors.lastname: Morbiducci
authors.forename: Alberto
authors.initials: A
authors.lastname: Redaelli
authors.forename: Danny
authors.initials: D
authors.lastname: Bluestein
mesh_terms: D000328:Adult; D000465:Algorithms; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D004867:Equipment Design; D006350:Heart Valve Prosthesis / Q000009:adverse effects; D006439:Hemodynamics; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D015233:Models, Statistical; D015539:Platelet Activation; D012306:Risk; D013314:Stress, Mechanical; D013923:Thromboembolism / Q000517:prevention & control; D013927:Thrombosis / Q000517:prevention & control; D013997:Time Factors