Hb S/ß-Thalassemia in the REDS-III Brazil Sickle Cell Disease Cohort: Clinical, Laboratory and Molecular Characteristics.

ABSTRACT

We described the clinical, laboratory and molecular characteristics of individuals with Hb S (HBB c.20A>T)/ß-thalassemia (Hb S/ß-thal) participating in the Recipient Epidemiology and Donor Evaluation Study (REDS-III) Brazil Sickle Cell Disease cohort. HBB gene sequencing was performed to genotype each ß-thal mutation. Patients were classified as Hb S/ß0-thal, Hb S/ß+-thal-severe or Hb S/ß+-thal based on prior literature and databases of hemoglobin (Hb) variants. Characteristics of patients with each ß-thal mutation were described and the clinical profile of patients grouped into Hb S/ß0-thal, Hb S/ß+-thal and Hb S/ß+-thal-severe were compared. Of the 2793 patients enrolled, 84 (3.0%) had Hb S/ß0-thal and 83 (3.0%) had Hb S/ß+-thal; 40/83 (48.2%) patients with Hb S/ß+-thal had mutations defined as severe. We identified 19 different ß-thal mutations, eight Hb S/ß0-thal, three Hb S/ß+-thal-severe and eight Hb S/ß+-thal. The most frequent ß0 and ß+ mutations were codon 39 (HBB c.118C>T) and IVS-I-6 (T>C) (HBB c.92+6T>C), respectively. Individuals with Hb S/ß0-thal had a similar clinical and laboratory phenotype when compared to those with Hb S/ß+-thal-severe. Individuals with Hb S/ß+-thal-severe had significantly lower total Hb and Hb A levels and higher Hb S, white blood cell (WBC) count, platelets and hemolysis markers when compared to those with Hb S/ß+-thal. Likewise, individuals with Hb S/ß+-thal-severe showed a significantly higher occurrence of hospitalizations, vaso-occlusive events (VOE), acute chest syndrome (ACS), splenic sequestration, blood utilization, and hydroxyurea (HU) therapy.