Protection from plasma cell-free hemoglobin and heme in sickle cell disease. The paper by Liu et al suggests 3 strategies to deal with the toxic consequences of intravascular heme in SCD. Haptoglobin is the first line of defense; it binds hemoglobin dimers in the plasma. Hemopexin is the second line of defense; it binds heme that has dissociated from hemoglobin that has not been bound by haptoglobin. Patrolling monocytes are the third line of defense; they scavenge microvascular endothelial cells that have been damaged by free heme. Hb, hemoglobin; SCD, sickle cell disease. Professional illustration by Patrick Lane, ScEYEnce Studios.