Role of AnxA1 in the resolution of neutrophil-dependent thromboinflammation in SCD and beyond. (A) Proresolving factors comprise lipid mediators, nucleic acids, and proteins, including cytokines and AnxA1. (B) AnxA1 is a glucocorticoid (GC)-regulated protein that mediates some of the anti-inflammatory effects of endogenous and synthetic GCs via its main receptor, FPR2/ALX. (C) In SCD, AnxA1 may act in neutrophils to downregulate the activity of ERK and Akt signaling pathways and promote cleavage of caspase 3, resulting in a switch from a proneutrophil extracellular trap (NET)-otic to apoptotic phenotype, thus reducing thromboinflammation. (D) Neutrophil reprogramming via AnxA1 and its related peptides may have therapeutic potential in a broad range of diseases where NETosis contributes to pathogenesis.