Liver-to-lung NET embolization in SCD. Hemolysis releases DAMPs that prime neutrophils and lead to the activation of an interferon and gasdermin-D (GSDMD)-dependent signaling pathway, which promotes NET generation into the liver microcirculation. These NETs carried through the blood into the lungs can then promote neutrophil-platelet aggregation, leading to pulmonary vasoocclusion.