Comparative study on efficacy of thrombolytic protocols: Dual therapy against standard tPA regimen

Abstract

When a blood clot occludes cerebral arteries and causes a stroke, a common cause of global death, thrombolytic therapy steps in as a highly effective treatment to restore the blood flow by dissolving the clot. Thrombolytic therapy is the use of plasminogen activators, including tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), either separately or in combination. In this study, a mathematical model of thrombolysis has been developed for nonuniform fibrin clots, which have varying density levels nearer and farther from the cell surface. The non-Newtonian nature of blood flow and the viscoelasticity of vessel walls are considered. The dynamic of the pulsatile flow is described using the mass and momentum conservation laws with the Carreau viscosity model, and the generalized Maxwell model is used for the vessel wall. The transport of drugs and fibrinolytic factors involved in the dissolution process induced by convection and diffusion is considered. The developed model can predict the clot lysis pattern in combined drug therapies and can be used to optimize the drug dosage required for treatment. The model is used to evaluate the safety of dual thrombolytic therapy with tPA bolus and uPA continuous infusion in three different doses and then compared with the FDA-approved regimen and experimental studies. Results show that although dual thrombolytic therapy is safe and does not increase the risk of bleeding, it is not more effective than the FDA-approved regimen in faster clot dissolution and restoration of blood flow.