A structural and mechanical assessment of thrombus analogs formed under physiological pressure and flow

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Abstract

BACKGROUND - The success of the mechanical thrombectomy treatment in acute ischemic stroke is highly dependent on mechanical clot behavior and characteristics like stiffness. This mechanical treatment is tested in clot analogs. Realistic clot analogs could potentially be made in a realistic formation environment. The effects of blood pressure and flow were mimicked in this study. Factors affecting the mechanical behavior of thrombus analogs should be investigated to understand treatment possibilities better.METHODS - First, the effect of blood pressure was mimicked in a static pressure experiment by putting a weight on blood which generates a constant force. The clot analogs were mechanically assessed by unconfined compression testing. The effect of whole blood clot formation under pressure, the effect of different heights, and the effect of different hematocrit levels (a volumetric hematocrit of
1%H, 40%H, and 99%H) were investigated. Secondly, fibrin clots are formed by clotting platelet poor plasma on tissue factor under flow, with four different shear rates (shear=0/s, 50/s, 150/s, and 300/s). These clots were assessed by micro-indentation and confocal imaging. RESULTS - A total of 50 clot analogs under static conditions were successfully analyzed. Hyperelastic strain stiffening and visco-elastic behavior was seen in all clots, higher heights resulted in a higher stiffness in strain >60%, and 1%H clots were stiffer than 99%H clots. Furthermore, a total of 43 fibrin clots formed under flow were successfully investigated. It was seen that flow reduced the clot
heights, fibers seemed to align with the flow direction, flow reduced the density in the top of the clots, and clots formed under shear had a higher stiffness than similar statically formed clots.
CONCLUSION - A range of clot analogs under static conditions and flow were made and tested. The significant differences in mechanical properties and microstructure found can have new implications in thrombectomy research.