Inclusion Criteria:  Provision of consent Female patients of childbearing potential must use highly effective methods of contraception, male patients are willing to use barrier methods of contraception  Cohort A (Sickle Cell Disease Transfusion Cohort)  Confirmed diagnosis of sickle cell disease Chronically red blood cell transfused for primary stroke prevention or due to previous stroke. Chronic red blood cell transfusion is defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period Receiving chronic red blood cell transfusion by straight transfusions At least 24 months of chronic monthly red blood cell transfusions for primary stroke prevention or treatment of primary stroke (initial completed overt clinical stroke with document infarction on brain computed tomography [CT] or magnetic resonance imaging [MRI]) On iron chelation therapy for > 3 months prior to enrollment Documented adequate monthly transfusions with average HbS ≤ 45% (the upper limit of the established academic community standard) for the previous 12 weeks of red blood cell transfusions before the first dose of study treatment  Cohort B (Thalassemia Transfusion Cohort)  Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia) Chronically transfused, defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period On iron chelation therapy for > 3 months prior to enrollment  Cohort C (Thalassemia Non-transfused Cohort)  Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia) Hemoglobin ≤ 10 g/dL  Exclusion Criteria:  Female who is breast feeding or pregnant  Hepatic dysfunction characterized by:  Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) Direct bilirubin > 3.0 × ULN History of cirrhosis Known human immunodeficiency virus (HIV) positivity Active hepatitis B or hepatitis C infection Severe renal dysfunction or on chronic dialysis  History of malignancy within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation.  Patients with malignancy considered surgically cured are eligible (eg, non- melanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [Stage 1], Grade 1 endometrial cancer)  History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:  Unstable angina pectoris or myocardial infarction or elective coronary intervention Congestive heart failure requiring hospitalization Uncontrolled clinically significant arrhythmias Symptomatic pulmonary hypertension