Rheometrical and molecular dynamics simulation studies of incipient clot formation in fibrin-thrombin gels: An activation limited aggregation approach

A rheometrical investigation of incipient clots formed in fibrin-thrombin gels is reported in which the Gel Point (GP) is characterised by frequency independence of the loss tangent in small amplitude oscillatory shear measurements over a wide range of thrombin concentration. Values of the fractal dimension (Df) of the GP network calculated from measurements are consistent with those reported in simulations of diffusion limited cluster–cluster aggregation (DLCCA) and reaction limited cluster–cluster aggregation (RLCCA), but differ insofar as the values of Df calculated from the present experiments increase progressively with a reduction in gel formation time. A molecular dynamics simulation (MDS) of systems of rod-like particles was designed to (i) test the hypothesis that the presence of an activation profile in a cluster aggregation model could account for the trend of Df as a function of gel formation time observed experimentally in fibrin-thrombin gels and whole heparinised blood without recourse to the inclusion of fibrinogen-specific interactions; and (ii) to explore the effect of monomer activation kinetics on the microstructure of fractal clusters formed in systems of rigid rod-like particles. The results identify two possible mechanisms for the increase in Df as the gel formation time decreases, both being a consequence of altering the evolution of the clustering dynamics by a process referred to herein as activation limited aggregation (ALA). This ALA-based MDS substantiates the experimental findings by confirming the trend evident in the formation of incipient clots in fibrin-thrombin gels and in whole heparinised blood. A mechanism for ALA involving the aggregation of pre-GP sub-clusters is proposed.

► A mechanism for altering the evolution of clustering dynamics in fractal aggregates is proposed. ► The MDS study reinforces the diagnostic potential of characterizing clot structure. ► Rheometry reveals the fractal characteristics of incipient fibrin clot networks.