Original Contributions to Biofluid Mechanics Theory for Cardiovascular Device Design in Patients with Sickle Cell Disease

Sickle cell disease profoundly alters blood rheological and microcirculatory properties in ways that make the haemodynamic assumptions underlying standard cardiovascular device design criteria potentially inapplicable to sickle cell disease patients, yet the theoretical biofluid mechanics of sickle cell blood has not been systematically incorporated into cardiovascular device design theory. This dissertation makes original contributions to biofluid mechanics theory for cardiovascular device design in sickle cell disease patients, developing revised haemodynamic models that incorporate sickle cell disease-specific blood properties and using them to generate device design guidance. The dissertation addresses three cardiovascular device categories with significant relevance to Nigerian sickle cell disease patients: venous access port systems for chronic transfusion therapy, microfluidic blood exchange systems for hydroxyurea drug delivery monitoring, and computational fluid dynamics models for total artificial heart shear stress haemolysis prediction in sickle cell disease patients. Original theoretical contributions include a generalized non-Newtonian blood flow constitutive model parameterized with sickle cell disease-specific viscosity-shear rate relationships measured from patient blood samples collected at the Lagos University Teaching Hospital; a theoretical microvascular obstruction probability model incorporating the stochastic nature of sickling under varying oxygen tension and flow conditions; and a critical shear stress threshold theory for haemolysis initiation in sickle cell erythrocytes, which are known to be significantly more mechanically fragile than normal erythrocytes. The theoretical developments are validated against in vitro flow experiments and against clinical haemolysis data from patients on extracorporeal circuits. Keywords: biofluid mechanics, sickle cell disease, cardiovascular devices, haemodynamics, Nigeria.