Mathematical modeling of blood clot fragmentation during flow-mediated thrombolysis.

A microscale mathematical model of blood clot dissolution based on coarse-grained molecular dynamics is presented. In the model, a blood clot is assumed to be an assembly of blood cells interconnected with elastic fibrin bonds, which are cleaved either biochemically (bond degradation) or mechanically (bond overstretching) during flow-mediated thrombolysis. The effect of a thrombolytic agent on biochemical bond degradation was modeled phenomenologically by assuming that the decay rate of an individual bond is a function of the remaining noncleaved bonds in the vicinity of that bond (spatial corrosion) and the relative stretching of the bond (deformational corrosion). The results of simulations indicate that the blood clot dissolution process progresses by a blood-flow-promoted removal of clot fragments, the sizes of which are flow-dependent. These findings are in good agreement with the results of our recent optical-microscopy experimental studies on a model of blood clot dissolution, as well as with clinical observations. The findings of this study may contribute to a better understanding of the clot fragmentation process and may therefore also help in designing new, safer thrombolytic approaches.