Investigating the two regimes of fibrin clot lysis: an experimental and computational approach

Abstract

It has been observed in vitro that complete clot lysis is generally preceded by a slow phase of lysis during which the degradation seems to be inefficient. However, this slow regime was merely noticed, but not yet quantitatively discussed. In our experiments, we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast lysis regime. We quantified extensively the duration of these regimes for a wide spectrum of experimental conditions and found that on average, the slow regime lasts longer than the fast one, meaning that during most of the process, the lysis is ineffective. We proposed a computational model in which the properties of the binding of the proteins change during the lysis: first, the biochemical reactions take place at the surface of the fibrin fibers, then in the bulk, resulting in the observed fast lysis regime. This simple hypothesis appeared to be sufficient to reproduce with a great accuracy the lysis profiles obtained experimentally.

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

“…Although the biochemistry of fibrinolysis is well understood 5 , our knowledge of many aspects of the complete process in vivo and in vitro remains sparse 6 , 7 . For example, the permeability of the thrombus, which is central to the transport of active macromolecules in the bloodstream, is only estimated via indirect measurements like perviousness 8 ; the exact amount of drug that reaches the thrombus is unknown; even the dynamics of fibrin strands degradation is still actively investigated 9 – 14 . Even though patients who receive early intervention show a better three-month prognosis, about fifty percent fail to respond, and the reasons for this are unknown.…”

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

“…the exact amount of drug that reaches the thrombus is unknown; even the dynamics of fibrin strands degradation is still actively investigated [9][10][11][12][13][14] . Even though patients who receive early intervention show a better threemonth prognosis, about fifty percent fail to respond, and the reasons for this are unknown.…”