TLR4 and sickle cell disease: This mechanism has been suggested to contribute to the chronic inflammatory state that is observed in sickle cell disease.10 Furthermore, various studies in sickle cell disease mouse models have demonstrated that the injection of heme solutions can trigger endothelial hyperactivation, leading to vasoocclusion or an acute chest syndrome‐like phenotype.11, 27 Purified heme was found to be an activator of TLR4 8, 11, 27 in some studies and of the inflammasome 9 in others, and these activities were considered to be the molecular mechanism behind the coexistence of inflammation and hemolysis.