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

We described the clinical, laboratory and molecular characteristics of individuals with Hb S (HBB: c.20A>T)/β-thalassemia (Hb S/β-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 β-thal mutation. Patients were classified as Hb S/β⁰-thal, Hb S/β⁺-thal-severe or Hb S/β⁺-thal based on prior literature and databases of hemoglobin (Hb) variants. Characteristics of patients with each β-thal mutation were described and the clinical profile of patients grouped into Hb S/β⁰-thal, Hb S/β⁺-thal and Hb S/β⁺-thal-severe were compared. Of the 2793 patients enrolled, 84 (3.0%) had Hb S/β⁰-thal and 83 (3.0%) had Hb S/β⁺-thal; 40/83 (48.2%) patients with Hb S/β⁺-thal had mutations defined as severe. We identified 19 different β-thal mutations, eight Hb S/β⁰-thal, three Hb S/β⁺-thal-severe and eight Hb S/β⁺-thal. The most frequent β⁰ and β⁺ mutations were codon 39 (HBB: c.118C>T) and IVS-I-6 (T>C) (HBB: c.92+6T>C), respectively. Individuals with Hb S/β⁰-thal had a similar clinical and laboratory phenotype when compared to those with Hb S/β⁺-thal-severe. Individuals with Hb S/β⁺-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/β⁺-thal. Likewise, individuals with Hb S/β⁺-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.