Intravenous heme is lethal in HbSS, but not HbAA, mice and inhibition of TLR4 signaling with TAK-242 rescues HbSS mice. All HbSS and HbAA mice (n = 6 mice per treatment) were given a bolus infusion of heme (32 µmol/kg) at time zero. One treatment group received TAK-242 (2 mg/kg, IP) 30 minutes before heme infusion. Time of death after heme infusion was recorded.