A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions.

One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient's bloodstream, which breaks down the thrombi's fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model's results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.

Thrombolysis: Observations and numerical models.

This perspective paper considers thrombolysis in the context of ischemic strokes, intending to build eventually a numerical model capable of simulating the thrombolytic treatment and predicting patient outcomes. Numerical modeling is a scientific methodology based on an abstraction of a system but requires understanding their spatio-temporal interactions. However, although important, the current knowledge on thrombolysis is fragmented in contributions from which it is difficult to obtain a complete picture of the process, especially in a clinically relevant setup. This paper discusses, from a general point of view, how to develop a numerical model to describe the evolution of a patient clot under the action of a thrombolytic drug. We will present critical, yet fundamental, open questions that have emerged during this elaboration and discuss original experimental observations that challenge some of our current knowledge of thrombolysis.