The identification of novel therapeutic targets, like platelet activation shown here, builds upon established interventions to diagnose sickle cell disease and prevent and treat complications. These approaches may complement one another, with standard of care serving as a foundation for exploratory approaches. P2Y12 inhibition, at the top of the figure, is the mechanism affected by ticagrelor. While inhibition of this transmembrane molecule blocks platelet activation (and aggregation via increase GP IIb/IIIa expression), there are other important mechanisms that are candidates that may be additive or alternative to P2Y12 inhibition. The red question marks indicate targetable mechanisms that have been investigated with preclinical animal and in vitro models. There is particularly robust preclinical data to support targeting plateletneutrophil interactions. Meanwhile, the standard of care, including universal newborn screening, immunizations, and antibiotic prophylaxis in childhood, needs to be expanded to include people with sickle cell disease living in low and middle income countries, regardless of participation in clinical trials.