3. History of ≥ 2 severe vaso-occlusive pain crises (VOC) per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea). A severe VOC is defined as an episode of pain lasting more than 2 hours severe enough to require care at a medical facility. Note that priapism that lasts more than 2 hours and requires care at a medical facility is also considered a VOC.