Flowchart for the dose escalation study of mitapivat in SCD. ∗Subject 4 was withdrawn because of the need for medical intervention for pulmonary embolism present unknowingly at enrollment and unrelated to drug; the subject was lost to follow-up and not evaluable for laboratory response. ∗∗Subject 10 self-discontinued therapy before completing the 100-mg dose level because of an AE unrelated to the drug; analyzed with the 50-mg dose cohort.