Release of cell-free heme activates converging inflammatory pathways, such as TLR4 signaling [58], formation of neutrophil extracellular traps (NETs) [24,59], and priming of the inflammasome (NLRP3) pathway, leading to the release of interleukin-1β (IL-1β) and IL-18 by leukocytes, platelets, and endothelial cells, which contributes to the development of a sterile thrombo-inflammatory state in SCD [28,51,60,61]. Here, IL1B is linked to Schnyder corneal dystrophy.