Co-inheritance of a-thalassemia dramatically decreases the risk of acute splenic sequestration in a large cohort of newborns with hemoglobin SC Hemoglobin SC (HbSC) is the second most common variant of sickle cell disease worldwide after Hb SS. Hb C is caused by a mutation in the seventh codon of the HBB gene [HBB:c.19G>A(p.Glu7Lys)]. The β S allele is associated with different β S haplotypes that are named according to the region in which they originated, 1 although such multicentric origin of the β S allele has recently been proven to be unreliable. 2 In addition to this anthropological importance, different β S haplotypes can modulate the severity of sickle cell anemia. 3 β C haplotypes I, II, and III were first described by Boehm et al. 4 There are no data in the literature on the association of β C haplotypes with clinical and hematologic features. Likewise, the effect of co-inheritance of a-thalassemia (a-thal) in patients with HbSC is still unclear.This study was based on a retrospective cohort of 461 newborns from Minas Gerais, Brazil (birth date: 01/01/1999 to 31/12/2012). Results on the clinical and hematologic profiles have been recently published. 5 Methods for the determination of a-thal and β-globin gene cluster haplotypes, as well as detailed statistical methods are available in the Online Supplementary Appendix S1. P<0.01 was considered significant. The study was approved by the institutional research ethics committee (protocol 13327713.5.0000.5149).Co-inheritance of a-thal was determined in 389 children; 77 (19.8%) were -a 3.7 /aa and one (0.26%) -a 3.7 /-a 3.7 ; 311 (79.9%) had wild HBA alleles (aa/aa). The patients were analyzed for a follow up of a total of 3,522.72 patient-years. There was no difference in follow up between the two groups (8.78 and 9.13 years for patients with or without co-inheritance of a-thal, respectively; P=0.51). The incidence of pain crises for all those 389 children was 52.1 episodes per 100 patient-years (95%CI: 49.8-54.6). The incidence of infections was 60.1 events per 100 patient-years (95%CI: 57.6-62.7), and that of red blood cell (RBC) transfusions, 4.4 events per 100 patient-years (95%CI: 3.73-5.15).The risks of pain crises, infections, and RBC transfu-