HMGB1 and ischemia: During ischemia, pre-apoptotic RBCs and other blood cells release damage-associated molecular patterns (DAMPs), such as ATP (hemolysis and necrotic cells), heme (hemolysis), high-mobility group box 1 (HMGB1) (necrotic cells), and heat shock proteins (hemolysis and necrotic cells), parameters of which are increased in SCD [195,196].