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Although quantitative ultrasound techniques based on the parameterization of the backscatter coefficient (BSC) have been successfully applied to blood characterization, theoretical scattering models assume blood as an isotropic scattering medium. However, the red blood cell (RBC) aggregates form anisotropic structures such as rouleaux. The present study proposes an anisotropic formulation of the effective medium theory combined with the local monodisperse approximation (EMTLMA) that considers perfectly aligned prolate-shaped aggregates. Theoretical BSC predictions were first compared with computer simulations of BSCs in a forward problem framework. Computer simulations were conducted for perfectly aligned prolate-shaped aggregates and more complex configurations with partially aligned prolate-shaped aggregates for which the size and orientation of RBC aggregates were obtained from blood optical observations. The isotropic and anisotropic EMTLMA models were then compared in an inverse problem framework to estimate blindly the structural parameters of RBC aggregates from the simulated BSCs. When considering the isotropic EMTLMA, the use of averaged BSCs over different insonification directions significantly improves the estimation of aggregate structural parameters. Overall, the anisotropic EMTLMA was found to be superior to the isotropic EMTLMA in estimating the scatterer volume distribution. These results contribute to a better interpretation of scatterer size estimates for blood characterization. [ABSTRACT FROM AUTHOR]