The phenotypes of sickle cell disease: strategies to aid the identification of undiagnosed patients in the Italian landscape

Sickle cell disease (SCD) is an inherited autosomal recessive monogenic blood disorder characterized by red blood cell sickling responsible for recurrent vaso-occlusive crises and chronic hemolysis. Clinical manifestations vary and SCD patients experience increased morbidity and mortality. In Italy, SCD patients cluster into two distinct subpopulations: those of sub-Saharan African descent and those of Caucasian descent. Most sub-Saharan African SCD patients are children or young adults and carry the homozygous genotype hemoglobin (Hb) S, or SC, whereas Caucasian SCD patients tend to be older and have predominantly HbS/β-thalassemia. Patients of African descent typically present with acute SCD-related events, including vaso-occlusive crises, acute chest syndrome, anemia, fever, and pneumonia. Caucasian patients, according to the different distribution of SCD genotypes, may exhibit either acute episodes or chronic long-term complications. Regardless of age, genotype, or ethnic background, most SCD patients in Italy are undiagnosed, and pain, fatigue and anemia should be regarded as presenting signs and symptoms of this disease. The tests needed to diagnose SCD are simple, and a complete blood count together with erythrocyte morphology, wherever available, hemolysis markers, should be performed whenever SCD is suspected. If a patient presents with two risk factors –family history, ethnicity, or a significant clinical feature – a first-level screening test (e.g. assessment of Hb fractions with HPLC), where available, should be performed immediately, or a referral should be provided. Here, we present an overview of the clinical features of SCD that may be encountered in real-world clinical practice in Italy from a practical perspective. This narrative review may aid non-specialist physicians in identifying disparate clinical conditions that may be symptoms or signs of SCD.