The Development of a Novel in vitro Flow System to Evaluate Platelet Activation and Procoagulant Potential Induced by Bileaflet Mechanical Heart Valve Leakage Jets
Fallon, Anna Marie
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Bileaflet mechanical heart valves (BMHVs) are prone to thrombus formation in the hinge region due to high shear stress combined with stagnation regions. This thesis research addresses the hypothesis that models that isolate and mimic BMHV hinge geometries can be used to quantitatively characterize procoagulant potential using a novel in vitro blood flow system. Furthermore, these results can be correlated with digital particle image velocimetry (DPIV) measurements detailing flow fields for the same models. The significant findings were that: 1) recalcification of recirculating citrated blood markedly increases the magnitude of thrombus forming reactions and the sensitivity for their detection; 2) platelet activation, and the presence of adequate platelet numbers are essential for the activation of coagulation under conditions of high shear; and 3) thrombin formation can be inhibited by blocking the platelet receptors that facilitate platelet aggregation. The DPIV studies give some insight into why different channel geometries resulted in varying propensities for coagulation. The channel geometries with abrupt changes in diameter induced significantly higher levels of TAT and also formed jets that were subject to increased entrainment of the stagnant fluid in the chamber. This entrainment enables more mixing of the shear-activated platelets with the surrounding flow, which can propagate the coagulation cascade, thus increasing the chance for thrombus formation. The influence of abrupt changes in diameter was also evident in the BMHV human blood studies. The MP valve, which has a tortuous hinge pathway, induced significantly more TAT formation than the SJM Standard valve with a smoother hinge channel. Thus, BMHV hinge geometry should be as smooth and free of diameter changes as possible to eliminate stagnation regions that enable activated platelets to congregate and propagate the coagulation cascade. Leakage gap width also had a significant effect not only on procoagulant potential but also on platelet activation. Both the low and high leaker prototype valves had significantly higher levels of platelet activation compared to the SJM Standard valve, but only the low leaker valve demonstrated a higher propensity for coagulation. Thus, to minimize both platelet activation and thromboemboli formation, an optimal gap width should be maintained for BMHVs.