Figure 3. A hypothetical timeline of events that can promote thrombosis due to superficial erosion.

This hypothetical timeline depicts a possible sequence of events (from left to right) that can lead to thrombosis due to superficial erosion. Endothelial cells can undergo low-grade smoldering activation as depicted by assuming a less squamous and more columnar morphology. Candidate stimuli include TLR2 ligands such as hyaluronan fragments among other innate immune activators including damage-associated molecular patters (DAMPs.) Endothelial cells with severed tethers to the basement membrane or those that have undergone various forms of cell death as depicted in Figure 2 can desquamate allowing access of platelets and neutrophils to subendothelial structures. Activation of platelets by contact with collagen and triggering of NETosis in the localized granulocytes can initiate and propagate the formation of a platelet-rich thrombus depicted on the right-hand side of this diagram showing activated platelets that can bridge through fibrin binding and adhere to collagen through glycoprotein VI. The red spiral structures in the platelet-rich thrombus depict DNA strands derived from NETs, decorated with thrombogenic and pro-inflammatory mediators as shown in Figure 4. (Illustration Credit: Ben Smith).