Multi-scale model for simulating thrombus formation and anticoagulant treatment

Abstract

Thrombosis is the localised clotting of blood and has a significant impact on medicine. Thrombi are formed by the activation of a series of events in the coagulation cascade. One way to prevent thrombus formation is by administering anticoagulants, which are drugs that target specific proteins in this cascade. In this work, a coagulation cascade model was developed. It provides a valuable tool for understanding the complex dynamics of thrombus formation and the role of the coagulation factors. Specifically, this model describes the temporal behaviour of several key components, including the tissue factor/factor VII complex, factor XI, factor IX, factor X, prothrombin, thrombin, factor VIII, factor V, protein C, peptide P, inactive and active fibrinogen, fibrin matrix and three intermediate complexes. The increase in viscosity that occurs as the thrombus develops is also described. The influence of tissue factor, factor XI and prothrombin on thrombus formation was also analysed through a sensitivity analysis. Prothrombin was found to have a major influence, as it is the precursor of thrombin, a crucial factor in the coagulation cascade. The coagulation cascade model was coupled to a fluid simulation of an idealised aneurysm, providing a comprehensive view of the spatial-temporal distribution of the coagulation factors based on the integration of residence time. The mapping of coagulation factors allows for a more realistic representation of physiological conditions. Inside the aneurysm, higher concentrations of coagulation factors were observed, as well as the presence of vortices, suggesting thrombus formation inside the aneurysm. In addition, the effect of the anticoagulant warfarin was incorporated into the coagulation cascade model. While warfarin successfully lowered the concentrations of the coagulation factors and delayed their activation, it was insufficient to prevent thrombus formation, as the same concentration was achieved as without anticoagulant.