Thrombin activity confinement and dense granule release drive the dynamics of arterial thrombus
Fig 5
Mechanism of thrombus growth and occlusion in the in silico simulations of FeCl3-unduced thrombosis.
A) Model geometry. 2D computational domain consisted of a rectangle representing the vessel and a segment representing the injury site zone. Vessel height was 0.5 mm, vessel length was 42.5 mm. Injury site length was 1 mm. Injury site zone coincided with the zone of thrombin generation. Green color marks the injury site zone. B)-F) show the data from the same simulation which ended in vessel occlusion at 248.6 second. Maximal thrombin flux was 2 pmol/(m2 ⋅ s). At all of the images flow direction was from top to the bottom. B) Image of the thrombus at the time of occlusion. Vessel lumen is brown, thrombus core is dark blue, while thrombus shell is blue. Color bar shows the values of porosity corresponding to colors on the image. C) Platelet activation state at the time of occlusion. Platelets reversibly activated by ADP are shown in green, platelets irreversibly activated by thrombin are shown in brown, vessel lumen is blue. D) The profile of thrombin at the time of occlusion. Color bar shows the values of concentration (unit [nM]) corresponding to colors on the image E) Profile of ADP at the time of occlusion. Color bar designations correspond to panel “D”. F) Profile of dense granule density inside the thrombus at the time of occlusion. Color bar shows the values of dense granule density (arbitrary units) corresponding to the colors on the image. G) Thrombus growth at intermediate value of maximal thrombin flux. Image of a non-occlusive thrombus at 600 seconds. Vessel lumen is brown, thrombus core is dark blue, while thrombus shell is blue. Maximal thrombin flux was 1.5 pmol/(m2 ⋅ s). Color bar designations correspond to panel “B”. H) The effect of turning off the ADP release from platelet dense granules on thrombus growth. Image of a thrombus at 600 seconds. Vessel lumen is brown, thrombus core is dark blue, while thrombus shell is blue. Maximal thrombin flux was 3 pmol/(m2 ⋅ s). Color bar designations correspond to panel “B”. I) Temporal dynamics of a blood flow in the vessel in silico. Red line: simulation with maximal thrombin flux of 3 pmol/(m2 ⋅ s). Orange line: simulation with maximal thrombin flux of 2 pmol/(m2 ⋅ s). Blue line: simulation with maximal thrombin flux of 1.5 pmol/(m2 ⋅ s). Green line: simulation with maximal thrombin flux of 3 pmol/(m2 ⋅ s), when the ADP release from platelet dense granules was turned off. J) Temporal dynamics of the thrombus area in the model simulations. Color designations correspond to panel “I”. K) Temporal dynamics of the thrombus core area in the model simulations. Color designations correspond to panel “I”.